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Yu-Chan Yang,1 Ke Zeng,2 Wei Wang,2 Zhi-Gang Gong,1 Yi-Lei Chen,1 Jian-Ming Cheng,1 Min Zhang,1 Yan-Wen Huang,1 Xin-Bo Men,2 Jian-Wei Wang,2 Songhua Zhan,1 Wen-Li Tan1 1Department of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Massage, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Songhua Zhan; Wen-Li TanDepartment of Radiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New Area, Shanghai, 201203, People’s Republic of China, Email zhansonghua@sina.com; 13764935974@163.comObjective: To investigate the changes of regional homogeneity (Reho) values before and after spinal manipulative therapy (SMT) in patients with chronic low back pain (CLBP) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI).Methods: Patients with CLBP (Group 1, n = 20) and healthy control subjects (Group 2, n = 20) were recruited. The fMRI was performed three times in Group 1 before SMT (time point 1, TP1), after the first SMT (time point 2, TP2), after the sixth SMT (time point 3, TP3), and for one time in Group 2, which received no intervention. The clinical scales were finished in Group 1 every time before fMRI was performed. The Reho values were compared among Group 1 at different time points, and between Group 1 and Group 2. The correlation between Reho values with the statistical differences and the clinical scale scores were calculated.Results: The bilateral precuneus and right mid-frontal gyrus in Group 1 had different Reho values compared with Group 2 at TP1. The Reho values were increased in the left precuneus and decreased in the left superior frontal gyrus in Group 1 at TP2 compared with TP1. The Reho values were increased in the left postcentral gyrus and decreased in the left posterior cingulate cortex and the superior frontal gyrus in Group 1 at TP3 compared with TP1. The ReHo values of the left precuneus in Group 1 at TP1 were negatively correlated with the pain degree at TP1 and TP2 (r = − 0.549, − 0.453; p = 0.012, 0.045). The Reho values of the middle temporal gyrus in Group 1 at TP3 were negatively correlated with the changes of clinical scale scores between TP3 and TP1 (r = 0.454, 0.559; p = 0.044, 0.01).Conclusion: Patients with CLBP showed abnormal brain function activity, which was altered after SMT. The Reho values of the left precuneus could predict the immediate analgesic effect of SMT.Keywords: blood-oxygen-level-dependent functional magnetic resonance imaging, spinal manipulation therapy, chronic low back pain, regional homogeneity

Perovskite solar cells (PSCs) can enable renewable electricity generation at low levelized costs, subject to the invention of an economically feasible technology for their large-scale fabrication, like vapor deposition. This approach is effective for the fabrication of small area (<1 cm 2 ) PSCs, but its scale-up to produce high-efficiency larger area modules has been limited by a severe imbalance between the vapor-solid reaction kinetics and the mass-transport of the volatile ammonium salt precursor. In this study, an amidine-based low-dimensional perovskite is introduced as an intermediate of the solid-vapor reaction to help resolve this limitation. This improves reaction pathway produces unique vertically monolithic grains with no detectable horizontal boundaries, which is used to produce 1.0 cm 2 PSCs with an efficiency of 22.1%, as well as 12.5 and 48 cm 2 modules delivering 21.1% and 20.1% efficiency, respectively. The modules retain ≈85% of their initial performance after 900 h of continuous operation (ISOS-L-1 protocol) and ≈100% after 2800 h of storage in an ambient environment (ISOS-D-1 protocol)., (© 2024 Wiley‐VCH GmbH.)

Selenoprotein M (SELENOM) has emerged as a crucial factor in maintaining cellular redox homeostasis and mitigating oxidative damage. This study aims to investigate its protective role in cardiac endothelial cells under hyperglycemic stress, a condition commonly associated with diabetes mellitus and its cardiovascular complications. Diabetic mice model and human umbilical vein endothelial cells (HUVECs) were applied for in vivo and in vitro studies. Results reveal that hyperglycemia significantly downregulates SELENOM expression in both diabetic mouse hearts and primary cultured cardiac endothelial cells. Overexpression of SELENOM in HUVECs mitigated high-glucose-induced FITC-Dextran diffusion and the loss of transendothelial electrical resistance. Additionally, SELENOM overexpression decreased reactive oxygen species (ROS) levels, preserved tight junction protein expression, and maintained cellular structural integrity under hyperglycemic conditions. Furthermore, SELENOM overexpression attenuated high-glucose-induced mitochondrial apoptosis. High-glucose conditions decreased Parkin and increased p62 and Beclin1 expressions. SELENOM overexpression restored Parkin levels and promoted co-localization of LAMP1 and TOMM20. Knockdown of Parkin significantly attenuated these protective effects, suggesting the importance of Parkin in Selenoprotein M-mediated mitophagy. Collectively, these findings suggest that Selenoprotein M enhances Parkin-mediated mitophagy to protect endothelial cells from hyperglycemic stress, offering potential therapeutic insights for diabetic cardiovascular complications., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients., Methods: A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors., Results: In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score <8; 74.10%), while daily exercise in recovery period (OR: 0.457, 95%CI: 0.229 ~ 0.913), a low-fat diet (OR: 0.600, 95%CI: 0.401 ~ 0.898) and the recovery time from 2 to 4 months (OR: 0.639, 95%CI: 0.445 ~ 0.918) were the protective factors., Conclusion: This is the first time to use the C19-YRSm scale to evaluate the health status in China. The study revealed prevalence of persistent symptoms within 120 days after Omicron onset., (© 2024. The Author(s).)

Transient osteoporosis of the hip (TOH) during pregnancy is a rare, self-limiting condition that frequently goes undiagnosed. However, if not managed properly, TOH can lead to significant complications, such as pathological fractures. We report a case of a 29-year-old primigravida at 33 weeks and four days of gestation who presented with a right femoral neck fracture following a fall. She had experienced prodromal hip pain for one month, initially misdiagnosed as pelvic girdle pain. Radiological evaluation revealed osteopenia and a sub-capital femoral neck fracture. Blood investigations were unremarkable. During hospitalisation, the patient was also diagnosed with asymptomatic COVID-19 infection, complicating the management approach. A multidisciplinary team decided on an elective caesarean section followed by closed manipulative reduction (CMR) and percutaneous screw fixation. Therefore, TOH in pregnancy requires timely diagnosis and intervention to prevent complications such as fractures. In cases complicated by concurrent conditions like COVID-19, multidisciplinary management is essential to ensure optimal outcomes for both mother and child., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tan et al.)

Problem: The terminal phase of childhood cancer poses profound physical and mental challenges for children, simultaneously influencing parents and rendering them particularly susceptible to psychosocial issues., Eligibility Criteria: This review included studies exploring the experiences of either: (1) paediatric terminal oncology patients aged under 18 years, (2) parents with a child facing terminal cancer undergoing palliative care, or (3) parents with a child who had undergone palliative care and died. English language, qualitative journal studies or grey literature of any care settings, geographical locations and publication years were included. Studies exploring the experiences of (1) paediatric terminal oncology not receiving palliative care from qualified healthcare professionals, and (3) non-biological parents or non-parental family members, were excluded., Sample: A total of 22 studies were included, published between January 2000 and December 2023. Seventy-two children (aged between 5 and 18 years old) and 236 parents (aged between 24 and 57 years old) participated across all studies. Palliative care settings mostly comprised oncology centres, hospitals and homes., Results: Two themes were identified from the 22 included studies: (1) Navigating rough waters and enduring hardships, and (2) Preparing for end-of-life amidst the looming threat of death., Conclusions: This review underscored the importance of integrating palliative childhood cancer care in a holistic, age-specific, family-centred, person-centred and timely manner., Implications: Paediatric oncology nurses should attend to physical and psychosocial needs of children and parents, fostering familial and social ties while recognising cultural and spiritual needs. Future research could recruit participants of varying ages, genders, and cultures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews., (© 2024. The Author(s).)

Objectives: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure., Materials and Methods: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS)., Results: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis., Conclusions: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr Saw reports grants from Astra Zeneca, consulting fees from Pfizer, Bayer, Astra Zeneca and Daiichi Sankyo, honoraria from Astra Zeneca, MSD, Bristol-Myers Squibb, Daiichi Sankyo, Roche and Takeda, meeting support from MSD and Astra Zeneca from Pfizer, advisory board participation from Astra Zeneca, Daiichi Sankyo and Pfizer, outside the submitted work. Dr Lai reports grants from Astra Zeneca, Roche and Amgen and meeting support from Astra Zeneca, outside the submitted work. Dr Chan reports meeting support from Roche, Astra Zeneca and Ipsen, outside the submitted work. Dr W.C. Tan reports grants from Singhealth, honoraria from Merck & Co, MSD and Astra Zeneca, meeting support from Ipsen Pharmaceuticals and Merck & Co, outside the submitted work. Dr A. Tan reports consulting fees from Amgen, Bayer and Pfizer, honoraria from Amgen, Guardant Health, Takeda, Juniper Biologics and Astra Zeneca, outside the submitted work. Dr W.L. Tan reports grants from Astra Zeneca, honoraria from Novartis and Merck, meeting support from Astra Zeneca, MSD, Boehringer Ingelheim and Ipsen, outside the submitted work. Dr Kanesvaran reports honoraria from Astellas, MSD and Ipsen, leadership roles in ESMO and SIOG, outside the submitted work. Dr Lim reports grants from Taiho Pharmaceuticals, consulting fees from Daiichi Sankyo, Amgen, Janssen and Alentis Therapeutics, honoraria from MSD and Takeda, meeting support from Astra Zeneca and Alentis Therapeutics, outside the submitted work. Dr. Tan reports grants from ACM Biolabs, Amgen, Astra Zeneca, Bayer and Pfizer, consulting fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, DKSH, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche and Takeda, honoraria from Amgen, Bayer, Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda, Beigene, Regeneron, Zymeworks, meeting support from Bayer, Merck, Pfizer, Regeneron and Zymeworks, outside the submitted work. Dr Mok reportsgrantsfrom AstraZeneca, Bristol Myers Squibb, G1 Therapeutics, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery, consulting fees from Abbvie Inc, ACEA Pharma, Adagene, Alentis Therapeutics AG, Alpha Biopharma Co., Ltd, Amgen, Amoy Diagnostics Co,AnHeart Therapeutics Inc,AVEO Pharmaceuticals, Inc,Bayer Healthcare Pharmaceuticals Ltd,BeiGene,BerGenBio ASA,Berry Oncology,Boehringer Ingelheim,Blueprint Medicines Corporation,Bristol Myers Squibb,Bowtie Life Insurance Company Limited,Bridge Biotherapeutics Inc,Covidien LP,C4 Therapeutics Inc,Cirina Ltd,CStone Pharmaceuticals,Curio Science,D3 Bio Ltd,Da Volterra,Daiichi Sankyo,Eisai,Elevation Oncology,F. Hoffmann-La Roche Ltd./ Genentech,Fishawack Facilitate Ltd,G1 Therapeutics Inc,geneDecode Co., Ltd,Gilead Sciences, Inc,GLG’s Healthcare,Gritstone Oncology, Inc,Guardant Health,Hengrui Therapeutics Inc,HiberCell, Inc.,HutchMed,Ignyta Inc.,Illumina Inc.,IncyteCorporation,Inivata,IQVIA,Janssen,Lakeshore Biotech Ltd,Lilly,Lunit USA, Inc,Loxo-Oncology,Lucence Health Inc,Medscape LLC/ WebMD,Medtronic,Merck Serono,MSD,Mirati Therapeutics Inc,MiRXES,MoreHealth,Novartis,Novocure GmbH,Omega Therapeutics Inc,OrigiMed,OSE Immunotherapeutics,PeerVoice,Pfizer,PrIME Oncology,Prenetics Global Limited,Puma Biotechnology Inc,Qiming Development (HK) Ltd,Regen Medtech Holdings Limited,Regeneron Pharmaceuticals Inc.,Roche Pharmaceuticals/ Diagnostics/ Foundation One,Sanofi-Aventis,SFJ Pharmaceutical Ltd,Simcere of America Inc,Synergy Research,Summit Therapeutics Sub, Inc,Takeda Pharmaceuticals HK Ltd,Tigermed,Vertex Pharmaceuticals,Virtus Medical Group,XENCOR, Inc,Yuhan Corporation,honorariafromACEA Pharma,Alpha Biopharma Co.Ltd,Amgen,Amoy Diagnostics Co. Ltd,AstraZeneca (before 1/1/19),BeiGene,BI,BMS,Daiichi Sankyo,Daz Group,Fishawack Facilitate Ltd.,InMed Medical Communication,Janssen Pharmaceutica NV,Jiahui Holdings Co. Limited,LiangYiHui Healthcare,Lilly,Lucence Health Inc.,MD Health Brazil,Medscape LLC,Merck Pharmaceuticals HK Ltd.,Merck Sharp & Dohme,MiRXES,Novartis,OrigiMed Co. Ltd.,P. Permanyer SL,PeerVoice, Physicians’ Education Resource,Pfizer,PrIME Oncology,Research to Practice,Roche Pharmaceuticals/ Diagnostics/ Foundation One,Sanofi-Aventis,Shanghai BeBirds Translation & Consulting Co. Ltd,Taiho Pharmaceutical Co. Ltd,Takeda Oncology,Touch Independent Medical Education Ltd,meeting support fromNovartis,Roche,Pfizer, AstraZeneca,Daiichi Sankyo,BI,MiRXES,BMS,MSD,Abbvie,Zai Lab,Liangyihui,advisory boardforAbbVie Inc.,ACEA Pharma,Amgen,AstraZeneca,Alentis Therapeutics AG,BerGenBio ASA,Berry Oncology,Blueprint Medicines Corporation,Boehringer Ingelheim,Bowtie Life Insurance Co Ltd,Bristol Myers Squibb,C4 Therapeutics Inc,Covidien LP,CStone Pharmaceuticals,Curio Science,D3 Bio Ltd.,Daiichi Sankyo Inc.,Eisai,Fishawack Facilitate Ltd.,G1 Therapeutics Inc.,Gilead Sciences Inc.,Gritstone Oncology Inc,Guardant Health,geneDecode Co. Ltd. (uncompensated),Hengrui Therapeutics Inc.,HutchMed,Ignyta Inc.,Incyte Corporation,Imagene AI Ltd.,Inivata,IQVIA,Janssen,Lakeshore Biotech,Lily,Loxo-Oncology Inc.,Lunit Inc,Merck Serono,Merck Sharp & Dohme,Mirati Therapeutics Inc.,MiRXES Group,Novartis,OrigiMed,Pfizer,Prenetics Global Limited,Puma Biotechnology Inc.,Roche/Genentech,Regeneron Pharmaceuticals Inc,Sanofi-Aventis R&D,SFJ Pharmaceutical,Simcere of America Inc.,Simcere Zaiming, Inc.,Takeda,Vertex Pharmaceuticals,Virtus Medical Group,XENCOR, Inc,Yuhan Corporation,being member in the Board of DirectorsforAstraZeneca PLC,HutchMed,Aurora,Insighta,holding stock / stock optionofAstraZeneca,Aurora Tele-Oncology Ltd.,Biolidics Ltd.,HutchMed,Prenetics Global Limited,D3 Bio,Lunit,Bowtie Life Insurance, Lakeshore Biotech Ltd,Loxo-oncology,Virtus Medical Group,Yinson Capital Pte. Ltd.,Phanes Therapeutics, Inc.,Insighta,Alentis Therapeutics AG, outside the submitted work. Dr Li reports grants from Gilead, MSD and Astra Zeneca, honoraria from Astra Zeneca, Novartis, Amgen, Pfizer. Takeda, ACE Oncology, Merck, Guardant Health, Gilead, Janssen and MSD, meeting support from Astra Zeneca, Pfizer, Daiichi Sankyo, MSD, Amgen, advisory board for Astra Zeneca, Pfizer, AnHeart Therapeutics, Amgen, Takeda, Yuhan and Blossomhill therapeutics, outside the submitted work. No other conflicts of interest were declared.]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Based on the N-redox mechanism, a turn-on near-infrared fluorescence probe (SWJT-15) with cyano isophorone as skeleton was designed and synthesized for the detection of ferrous ions (Fe 2+ ). The probe has a lower detection limit (83 nM) and fast response (200 s) to Fe 2+ ions. And the probe has unique selectivity and good anti-interference performance against Fe 2+ ions compared to other metal ions. Moreover, the probe has been successfully applied to imaging Fe 2+ ions in HeLa cells., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Non-small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these "nonsmoking-related oncogenes" (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and nonsmokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC data sets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to the regulation of the cell cycle. These findings suggest that, whereas the genomic landscape is similar between NSRO-driven NSCLC in smokers and nonsmokers, smoking still affects the tumor phenotype independently of genomic alterations., Significance: Non-small cell lung cancers driven by nonsmoking-related oncogenes do not harbor genomic scars caused by smoking regardless of smoking history, indicating that the impact of smoking on these tumors is mainly nongenomic., (©2024 American Association for Cancer Research.)

Inhalation of Aspergillus spp. can cause a wide spectrum of lung diseases. Endobronchial aspergilloma is an uncommon clinical entity that occurs because of Aspergillus spp. overgrowth in the airway lumen. We present a 73-year-old gentleman with a rare dual pathology of endobronchial aspergilloma and endobronchial adenocarcinoma. He initially presented with prolonged cough, dyspnoea, and haemoptysis. Bronchoscopy revealed an obstructed right main bronchus by a necrotic mass whereby histological examination showed evidence of Aspergillus spp. infection. The lesion however persisted despite treatment with anti-fungal agents. Repeated bronchoscopy and biopsy eventually unravelled an underlying endobronchial adenocarcinoma. He received chemotherapy but ultimately passed away 3 months later., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Ion migration is one of the most critical challenges that affects the stability of metal-halide perovskite solar cells (PSCs). However, the current arsenal of available strategies for solving this issue is limited. Here, novel perovskite active layers following the concept of ordered structures with functional units (OSFU) to intrinsically suppress ion migration, in which a three-dimensional (3D) perovskite layer is deposited by vapor deposition for light absorption and a 2D layer is deposited by solution process for ion inhibition, are constructed. As a promising result, the activation energy of ion migration increases from 0.36 eV for the conventional perovskite to 0.54 eV for the OSFU perovskite. These devices exhibit substantially enhanced operational stability in comparison with the conventional ones, retaining >85% of their initial efficiencies after 1200 h under ISOS-L-1. Moreover, the OSFU devices show negligible fatigue behavior with a robust performance under light/dark cycling aging test (ISOS-LC-1 protocol), which demonstrates the promising application of functional motif theory in this field., (© 2024 Wiley‐VCH GmbH.)

Background: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay., Methods: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples., Results: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001)., Conclusions: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The Scn3b gene encodes for Navβ3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined., Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55 mv and peaked at -25 mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (I Na ) at -25 mv. The parameters for half-maximal activation voltages (V 1/2 ) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups ( P  = 0.98 and P  = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V 1/2 and k (with P -values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ ( P  = 0.59) and late sodium current density ( P  = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization., Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak I Na activation current coupled with decreased cell surface expression of Nav1.5 and Navβ3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Fan, Wang, Cao, Li, Sun, Luo, Pan, Tan, Wu, Liu and Yu.)

Objective: To investigate the changes in amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC) values before and after acupuncture in young women with non-menstrual migraine without aura (MWoA) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI)., Methods: Patients with non-menstrual MWoA (Group 1, n = 50) and healthy controls (Group 2, n = 50) were recruited. fMRI was performed in Group 1 at 2 time points: before acupuncture (time point 1, TP1); and after the end of all acupuncture sessions (time point 2, TP2), and performed in Group 2 as a one-time scan. Patients in Group 1 were assessed with the Migraine Disability Assessment Questionnaire (MIDAS) and the Short-Form McGill Pain Questionnaire (SF-MPQ) at TP1 and TP2 after fMRI was performed. The ALFF and DC values were compared within Group 1 at two time points and between Group 1 and Group2. The correlation between ALFF and DC values with the statistical differences and the clinical scales scores were analyzed., Results: Brain activities increased in the left fusiform gyrus and right angular gyrus, left middle occipital gyrus, and bilateral prefrontal cortex and decreased in left inferior parietal lobule in Group 1, which had different ALFF values compared with Group 2 at TP1. The bilateral fusiform gyrus, bilateral inferior temporal gyrus and right middle temporal gyrus increased and right angular gyrus, right superior marginal gyrus, right inferior parietal lobule, right middle occipital gyrus, right superior frontal gyrus, right middle frontal gyrus, right anterior central gyrus, and right supplementary motor area decreased in activity in Group 1 had different DC values compared with Group 2 at TP1. ALFF and DC values of right inferior temporal gyrus, right fusiform gyrus and right middle temporal gyrus were decreased in Group1 at TP1 compared with TP2. ALFF values in the left middle occipital area were positively correlated with the pain degree at TP1 in Group1 (correlation coefficient r, r = 0.827, r = 0.343; P < 0.01, P = 0.015). The DC values of the right inferior temporal area were positively correlated with the pain degree at TP1 in Group 1 (r = 0.371; P = 0.008)., Conclusion: Spontaneous brain activity and network changes in young women with non-menstrual MwoA were altered by acupuncture. The right temporal area may be an important target for acupuncture modulated brain function in young women with non-menstrual MwoA., (© 2024. The Author(s).)

Hemorrhagic fever with renal syndrome (HFRS) is a significant public health problem in Hubei Province, China, where a novel strain of orthohantavirus, HV004, was reported in 2012. However, no systematic study has investigated the prevalence and variation of orthohantavirus in rodents and humans. Herein, 2137 small mammals were collected from ten HFRS epidemic areas in Hubei Province from 2012 to 2022, and 143 serum samples from patients with suspected hemorrhagic fever were collected from two hospitals from 2017 to 2021. Orthohantavirus RNA was recovered from 134 lung tissue samples from five rodent species, with a 6.27 % prevalence, and orthohantavirus was detected in serum samples from 25 patients. Genetic analyses revealed that orthohantavirus hantanense (HTNV), orthohantavirus seoulense (SEOV), and orthohantavirus dabieshanense (DBSV) are co-circulating in rodents in Hubei, and HTNV and SEOV were identified in patient serum. Phylogenetic analysis showed that most of the HTNV sequences were clustered with HV004, indicating that HV004-like orthohantavirus was the main HNTV subtype in rodents. Two genetic reassortments and six recombination events were observed in Hubei orthohantaviruses. In summary, this study identified the diversity of orthohantaviruses circulating in Hubei over the past decade, with the HV004-like subtype being the main genotype in rodents and patients. These findings highlight the need for continued attention and focus on orthohantaviruses, especially concerning newly identified strains., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Aims: Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab., Methods: Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes., Results: All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified., Conclusions: Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: The occurrence and disability of myocardial infarction (MI) are on the rise globally, making it a significant contributor to cardiovascular mortality. Irreversible myocardial apoptosis plays a crucial role in causing MI. Long non-coding RNAs (LncRNAs) are key regulators of the cardiac remodeling process. Therefore, it is necessary to explore the effect of LncRNAs on cardiomyocyte apoptosis in MI., Methods: The rat-MI model was constructed, LncRNA-Seq and qPCR analyses were used to determine differentially expressed genes obtained from heart tissue of rats in the MI and sham groups. The miRanda software was used to predict the binding sites of LncRNA-miRNA and miRNA-mRNA, which were futhrer verified by dual luciferase assay. The LncRNA-miRNA-apoptosis pathway was further validated using hypoxia-exposed primary cardiomyocytes., Results: Compared to the sham group, 412 LncRNAs were upregulated and 501 LncRNAs were downregulated in MI-rat heart tissues. Among them, LncRNA AC125982.2 was most significantly upregulated in MI-rat heart tissues and hypoxic cardiomyocytes. Knockdown of AC125982.2 and ATG4B expression reversed hypoxia-induced apoptosis. In addition, transfection of mir-450b-3p inhibitor attenuated the protective effect of AC125982.2 knockdown. Moreover, we found that AC125982.2 modulated ATG4B expression by acting as a sponge for miR-450b-3p., Conclusion: Upregulated AC125982.2 expression regulates ATG4B by sponging miR-450b-3p, promoting cardiomyocyte apoptosis and contributing to rat MI development., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: To compare the performance of droplet digital polymerase chain reaction (ddPCR) and plasma next-generation sequencing (NGS) in detecting clearance of plasma EGFR (pEGFR) mutations., Methods: Patients with treatment-naive advanced EGFR-mutated lung cancer treated with first-line tyrosine kinase inhibitors (TKIs) were included. pEGFR were measured at baseline and first response assessment using ddPCR and NGS. Clearance of pEGFR was defined as undetectable levels after a positive baseline result. Results were correlated with time-to-treatment failure (TTF). In exploratory analysis, corresponding change in carcinoembryonic antigen (CEA) levels was evaluated., Results: Between January 1, 2020, and December 31, 2021, 27 patients were recruited. Ex19del comprised 74% (20 of 27) and L858R 26% (seven of 27). Osimertinib was used in 59% (16 of 27), dacomitinib 4% (one of 27), and gefitinib/erlotinib 37% (10 of 27). Sensitivity of ddPCR and NGS in detecting pEGFR mutation at baseline was 70% (19 of 27) and 78% (21 of 27), respectively ( p  = 0.16). All patients with detectable pEGFR by ddPCR were detected by NGS.At a median of 8 (range 3-24) weeks post-TKI initiation, clearance of pEGFR was achieved in 68% (13 of 19) and 71% (15 of 21) using ddPCR and NGS, respectively. Concordance between ddPCR and NGS was 79% (kappa = 0.513, p  = 0.013). Clearance of pEGFR was associated with longer median TTF (not reached versus 6 months, p  = 0.03) and median decrease in CEA levels by 70% from baseline.In another cohort of 124 patients, decrease in CEA levels by greater than 70% within 90 days of TKI initiation was associated with doubling of both TTF and overall survival., Conclusions: Plasma NGS trended toward higher sensitivity than ddPCR in detecting pEGFR, although both had similar concordance in detecting pEGFR clearance. Our results support using NGS at diagnosis and interchangeability of NGS and ddPCR for monitoring, whereas CEA could be explored as a surrogate for pEGFR clearance., (© 2023 The Authors.)

The dramatic improvement of the PCE (power conversion efficiency) of organic photovoltaic devices in the past few years has been driven by the development of new polymer donor materials and non-fullerene acceptors (NFAs). In the design of such materials synthetic scalability is often not considered, and hence complicated synthetic protocols are typical for high-performing materials. Here we report an approach to readily introduce a variety of solubilizing groups into a benzo[ c ][1,2,5]thiadiazole acceptor comonomer. This allowed for the ready preparation of a library of eleven donor polymers of varying side chains and comonomers, which facilitated a rapid screening of properties and photovoltaic device performance. Donor FO6-T emerged as the optimal material, exhibiting good solubility in chlorinated and non-chlorinated solvents and achieving 15.4% PCE with L8BO as the acceptor (15.2% with Y6) and good device stability. FO6-T was readily prepared on the gram scale, and synthetic complexity (SC) analysis highlighted FO6-T as an attractive donor polymer for potential large scale applications.

The self-renew ability of cancer stem cells (CSCs) continues to challenge our determination for accomplishing cancer therapy breakthrough. Ineffectiveness of current cancer therapies to eradicate CSCs has contributed to chemoresistance and tumor recurrence. Yet, the discoveries of highly effective therapies have not been thoroughly developed. Further insights into cancer metabolomics and gene-regulated mechanisms of mitochondria in CSCs can expedite the development of novel anticancer drugs. In cancer cells, the metabolism is reprogrammed from oxidative phosphorylation (OXPHOS) to glycolysis. This alteration allows the cancer cell to receive continuous energy supplies and avoid apoptosis. The pyruvate obtained from glycolysis produces acetyl-coenzyme A (Acetyl-CoA) via oxidative decarboxylation and enters the tricarboxylic acid cycle for adenosine triphosphate generation. Mitochondrial calcium ion (Ca 2+ ) uptake is responsible for mitochondrial physiology regulation, and reduced uptake of Ca 2+   inhibits apoptosis and enhances cell survival in cancer. There have been many discoveries of mitochondria-associated microRNAs (miRNAs) stimulating the metabolic alterations in mitochondria via gene regulation which promote cancer cell survival. These miRNAs are also found in CSCs where they regulate genes and activate different mechanisms to destroy the mitochondria and enhance CSCs survival. By targeting the miRNAs that induced mitochondrial destruction, the mitochondrial functions can be restored; thus, it triggers CSCs apoptosis and completely eliminates the CSCs. In general, this review article aims to address the associations between miRNAs with mitochondrial activities in cancer cells and cancer stem cells that support cancer cell survival and self-renewal., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre (<7800 IU/ml) trend to better response and PFS. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrate early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Immune-subpopulation profiling also identifies specific PD-1 and CTLA-4 expressing CD8 subpopulations that predict for response to combined immune checkpoint blockade in NPC., (© 2023. The Author(s).)

Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg -1 ·d -1 , i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of β-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 μM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/β-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on β-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com )., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the second/subsequent line after resistance to first- and second-generation (1/2G) EGFR-TKI., Methods: We reviewed electronic records of 202 patients who received osimertinib from July 2015 to January 2019 in the second/subsequent line after progression on prior EGFR-TKI. Of these, complete data from 193 patients were available. Clinical data including patient characteristics, primary EGFR mutation, T790M mutation status, presence of baseline brain metastases (BM), first-line EGFR-TKI use, and survival outcomes were extracted, and results retrospectively analyzed., Results: Of 193 evaluable patients, 151 (78.2%) were T790M+ (T790M positive) with 96 (49.2%) tissue confirmed; 52% of patients received osimertinib in the second line setting. After median follow up of 37 months, median progression-free survival (PFS) of the entire cohort was 10.3 [95% confidence interval (CI): 8.64-11.50] months and median overall survival (OS) was 20 (95% CI: 15.61-23.13) months. Overall response rate (ORR) to osimertinib was 43% (95% CI: 35.9-50.3%); 48.3% in T790M+ vs . 20% in T790M- (T790M negative) patients. OS in T790M+ patients was 22.6 vs . 7.9 months in T790M- patients (HR 0.43, P=0.001), and PFS was 11.2 vs . 3.1 months respectively (HR 0.52, P=0.01). Tumour T790M+ was significantly associated with longer PFS (P=0.007) and OS (P=0.01) compared to tumour T790M- patients, however this association was not seen with plasma T790M+. Of the 22 patients with paired tumor/plasma T790M testing, response rate (RR) to osimertinib was 30% for those plasma T790M+/tumour T790M-, compared to 63% and 67% for those who were plasma T790M+/tumour T790M+ and plasma T790M-/tumour T790M+, respectively. By multivariable analysis (MVA), Eastern Cooperative Oncology Group (ECOG) performance status ≥2 was associated with shorter OS (HR 2.53, P<0.001) and PFS (HR 2.10, P<0.001), whereas presence of T790M+ was associated with longer OS (HR 0.50, P=0.008) and PFS (HR 0.57, P=0.027)., Conclusions: This cohort demonstrated the efficacy of osimertinib in second line/beyond for EGFR+ (EGFR mutation-positive) non-small cell lung cancer (NSCLC). Tissue T790M result appeared more predictive of osimertinib efficacy compared to plasma, highlighting potential T790M heterogeneity and the advantage with paired tumor-plasma T790M testing at TKI resistance. T790M- disease at resistance remains an unmet treatment need., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-661/coif). JM reports travel support for meetings from AstraZeneca. GGYL reports honoraria from Amgen and consulting/advisory role for Merck, AstraZeneca, Pfizer, Bristol Myers Squibb and Roche. MKA reports support for meetings from AstraZeneca, Boehringer Ingelheim, Ipsen; honoraria from Boston Scientific and consulting/advisory role for Merck. RK reports research funding support from Sanofi (Inst), Janssen Pharmaceuticals (Inst); honoraria from Astellas Pharma, Novartis, Janssen Pharmaceuticals, MSD Oncology, Bristol-Myers Squibb, consulting/advisory role for Pfizer, Astellas Pharma, Novartis, Mundipharma. TR reports honoraria and Speakers’ Bureau from Novartis, consulting/advisory role for Ipsen and Eisai. TKHL reports honoraria for AstraZeneca and consulting/advisory role for MSD. DSWT reports research funding from Novartis (Inst), GlaxoSmithKline (Inst), AstraZeneca (Inst); honoraria from Bristol-Myers Squibb, Takeda Pharmaceuticals, Novartis, Roche and Pfizer; consulting/advisory role for Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer. DWTL reports research funding from Bristol-Myers Squibb (Inst), honoraria from Boehringer Ingelheim, consulting/advisory role for Roche, AstraZeneca, MSD Oncology, Novartis and Boehringer Ingelheim and stock ownership from Clearbridge Biomedics. QSN reports research funding from Novartis, MSD Oncology and Bayer; honoraria from MSD Oncology, AstraZeneca and Pierre Fabre and consulting/advisory role for Boehringer Ingelheim. WLT reports educational grant support from AstraZeneca; honoraria from Novartis, Merck, and Amgen; support for meetings from AstraZeneca, Ipsen, Boehringer Ingelheim, Bristol-Myers Squibb (Inst), and DKSH. The other authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

Azulene has aroused widespread interest for constructing optoelectronic materials. However, controlling the dipole orientation of 2,6-azulene units in the conjugated polymer backbone is a significant challenge so far. Herein, by C-H activation strategy, three 2,6-azulene-TPD-based conjugated copolymers with different dipole arrangements were synthesized, where TPD = thieno[3,4- c ]pyrrole-4,6-dione. The dipole arrangements of 2,6-azulene units were random for P(AzTPD-1) , head-to-head/tail-to-tail for P(AzTPD-2) , and head-to-tail for P(AzTPD-3) . These polymers exhibited unipolar n-type semiconductor characteristics in organic field effect transistors. Moreover, regioregular polymer P(AzTPD-3) displayed the best device performance with an electron mobility of up to 0.33 cm 2 V -1 s -1 , which makes P(AzTPD-3) a high-performance n-type polymeric semiconductor. These results demonstrate that incorporation of 2,6-azulene units into the polymeric backbone together with the regulation of the dipole orientation of 2,6-azulene units is an effective strategy for obtaining high-performance organic optoelectronic materials.

The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state according to their respective environment. Ganoderma lucidum polysaccharide (GLPS) is a major bioactive component of Ganoderma lucidum , a well-known medicinal mushroom. Although the immunomodulatory and anti-tumor effects of GLPS have been proven, GLPS's effect on inhibiting hepatocellular carcinoma (HCC) by regulating macrophage polarization is little known. Our data showed that GLPS notably inhibited the growth of a Hepa1-6 allograft. The expression of M1 marker CD86 was higher in the tumor tissue of the GLPS treatment group than in the control group in vivo . In vitro , the phagocytic activity and NO production of macrophages were increased by GLPS treatment. Moreover, it was discovered that GLPS was able to increase the expression of the M1 phenotype marker CD86, iNOS, and pro-inflammatory cytokines comprising IL-12a, IL-23a, IL-27 and TNF-α, but inhibited macrophage polarization towards the M2 phenotype by decreasing the expression of CD206, Arg-1, and inflammation-related cytokines comprising IL-6 and IL-10. The data suggest that GLPS may regulate macrophage polarization. Mechanistically, GLPS increased the phosphorylation of MEK and ERK. In addition, the phosphorylation of IκBα and P65 was increased by GLPS treatment. These data showed that GLPS can regulate the MAPK/NF-κB signaling pathway responsible for M1 polarization. In a nutshell, our research puts forward a new application of GLPS in anti-HCC treatment by regulating macrophage polarization through activating MAPK/NF-κB signaling.

Conjugated polymer field-effect transistors are emerging as an enabling technology for flexible electronics due to their excellent mechanical properties combined with sufficiently high charge-carrier mobilities and compatibility with large-area, low-temperature processing. However, their electrical stability remains a concern. ON-state (accumulation mode) bias-stress instabilities in organic semiconductors have been widely studied, and multiple mitigation strategies have been suggested. In contrast, OFF-state (depletion mode) bias-stress instabilities remain poorly understood despite being crucial for many applications in which the transistors are held in their OFF-state for most of the time. Here, a simple method of using an antisolvent treatment is presented to achieve significant improvements in OFF-state bias-stress and environmental stability as well as general device performance for one of the best performing polymers, solution-processable indacenodithiophene-co-benzothiadiazole (IDT-BT). IDT-BT is weakly crystalline, and the notable improvements to an antisolvent-induced, increased degree of crystallinity, resulting in a lower probability of electron trapping and the removal of charge traps is attributed. The work highlights the importance of the microstructure in weakly crystalline polymer films and offers a simple processing strategy for achieving the reliability required for applications in flexible electronics., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Background: Given the escalating epidemic of obesity and diabetes coupled with redefined diagnostic criteria, it is critical to identify the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). We sought to determine the prevalence and mortality outcomes of MAFLD subtypes based on diagnostic criteria in the USA over the past three decades., Methods: Eleven cycles of the National Health and Nutrition Examination Surveys (NHANES; 1988-1994 and 1999-2020) were used, and 72,224 participants were included. MAFLD was defined according to the 2020 International Expert Consensus. Based on diagnostic criteria and risk factors, MAFLD was categorized into seven subtypes: type 1 (obesity subtype), 2 (metabolic unhealthy subtype), 3 (diabetes subtype), 4 (metabolic unhealthy non-diabetes subtype), 5 (obesity and diabetes subtype), 6 (metabolic unhealthy non-obesity subtype), and 7 (mixed subtype)., Results: Over the study period, the estimated prevalence of MAFLD increased significantly from 22% in 1988-1994 to 36% in 2017-2020. The prevalence of Type 4 was the highest, followed by that of Type 7, whereas other types were low and almost unchanged over time. Individuals with MAFLD had 19% and 38% increased mortality risks from all causes and cardiovascular disease, respectively. Among them, the metabolically unhealthy participants with normal weight demonstrated a 116% higher risk for all-cause mortality [hazard ratio (HR): 2.16, 95% CI: 1.52-3.08] and a 222% higher risk for cardiovascular mortality (HR: 3.22, 95% CI: 1.72-6.04). Interestingly, stratification and interaction analyses demonstrated a significant impact of metabolic parameters on the relationship between MAFLD and all-cause mortality., Conclusions: In conclusion, our study identified an increase in MAFLD prevalence and a significant association between metabolic derangements in MAFLD and all-cause or cardiovascular mortality., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest or financial ties to disclose., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of the anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We established that sfRNA is present in saliva using three different methods: northern blot, RT-qPCR and RNA sequencing. We next show that salivary sfRNA is protected in detergent-sensitive compartments, likely extracellular vesicles. In support of this hypothesis, we visualized viral RNAs in vesicles in mosquito saliva and noted a marked enrichment of signal from 3'UTR sequences, which is consistent with the presence of sfRNA. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in a human hepatoma cell line and human primary dermal fibroblasts. Transfection of 3'UTR RNA prior to DENV2 infection inhibited type I and III interferon induction and signaling, and enhanced viral replication. Therefore, we posit that sfRNA present in salivary extracellular vesicles is delivered to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yeh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We report the observation of a third crystalline polymorph, "form III", of the well-studied electron-transporting conjugated polymer P(NDI2OD-T2) that exhibits end-on texture. This third polymorph of P(NDI2OD-T2) is distinguished from other polymorphs by having two monomer units incorporated along the backbone-stacking direction, resulting in a doubling of the c axis of the unit cell. Form III crystallites are realized by melt-annealing a thin film followed by slow cooling. The distinct packing of this third polymorph is established through the application of grazing-incidence wide-angle X-ray scattering (GIWAXS) measurements combined with peak simulation of candidate unit cells. The discovery of a third polymorph of P(NDI2OD-T2) provides a fresh opportunity for studying structure/function relationships of this important semiconducting polymer.

Aims: Amongst patients with critical illness associated new onset AF (CI-NOAF), the risk of subsequent atrial fibrillation (AF) diagnoses and other adverse outcomes is unknown, and the role for long-term anticoagulation is unclear. This study sought to determine the factors associated with subsequent AF diagnoses and other adverse outcomes in this cohort., Methods and Results: Admissions to a tertiary general intensive care unit (ICU) between December 2015 and September 2018 were screened for AF episodes through hourly analysis of continuous ECG monitoring. Patients with a prior history of AF were excluded. AF burden was defined as the percentage of monitored ICU hours in AF. The primary endpoint was subsequent AF diagnoses, as collated from the statewide electronic medical records. Secondary endpoints included mortality, embolic events, MACE and subsequent anticoagulation., Results: Of 7030 admissions with 509 303 h of monitoring data, 309 patients with CI-NOAF were identified, and 235 survived to discharge. Subsequent AF diagnoses were identified in 75 (31.9%) patients after a median of 413 days. Increased AF burden had the strongest independent association with AF recurrence (OR = 15.03, P = 0.002), followed by increased left atrial area (OR = 1.12, P = 0.01). Only 128 (54.5%) patients had their AF diagnosis acknowledged at ICU discharge, and 50 (21.3%) received anticoagulation at hospital discharge., Conclusion: CI-NOAF is often under-recognized, and subsequent AF diagnoses are common post-discharge. AF burden during ICU admission has a strong independent association with subsequent AF diagnoses. Left atrial size is also independently associated with subsequent AF., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: To determine the prognostic value of programmed death-ligand 1 (PD-L1) score in early-stage epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), contrasted against EGFR-wildtype NSCLC., Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1st January 2010-31st December 2019 at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary end-points were 2-year disease-free survival (DFS) and 5-year overall survival (OS) by Kaplan-Meier method., Results: 455 patients were included (267 EGFR-mutated, EGFR-M+; 188 EGFR-wildtype, wt). Median age at diagnosis was 65 years, 52.3% (238/455) of patients were males, 62.9% (286/455) of patients were never-smokers and 92.5% (421/455) of patients had R0 resection. Stage IA comprised 42.4% (193/455) of patients, Stage IB comprised 23.1% (105/455) of patients, Stage IIA comprised 10.8% of patients (49/455), Stage IIB comprised 5.1% of patients (23/455) and Stage IIIA comprised 18.7% (85/455) of patients. Among EGFR-M+, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-M+ and EGFR-wt was 45.3% (121/267) and 54.8% (103/188) respectively (p = 0.047). At median follow-up of 47 months, 178 patients had relapsed. Among EGFR-M+, 2-year DFS comparing PD-L1 <1% and PD-L1 ≥1% was 78.1% and 67.6% (p = 0.007) while 5-year OS was 59.5% and 42.8% (p = 0.001), respectively. Controlling for age, gender, lymphovascular invasion, adjuvant therapy and resection margin status, PD-L1 ≥1% (hazard ratio, HR 2.18, 95% CI 1.04-4.54, p = 0.038), stage IIB (HR 7.78, 95% CI 1.72-35.27, p = 0.008) and stage IIIA (HR 4.45, 95% CI 1.44-13.80, p = 0.01) emerged as independent predictors of inferior OS on multivariable analysis. In exploratory analysis, genomic analysis of 81 EGFR-M+ tumours was performed. PD-L1 ≥1% tumours had significantly higher rates of TP53 mutations (36.1% versus 15.6%, p = 0.04), with predominantly missense mutations., Conclusion: PD-L1 ≥1% is an independent predictor of worse OS among early-stage EGFR-mutated NSCLC and is associated with inferior DFS regardless of EGFR status. PD-L1 score as a risk stratification factor should be evaluated in prospective adjuvant studies among EGFR-mutated NSCLC., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Saw reported receiving personal fees from Pfizer, Bayer, AstraZeneca and MSD outside the submitted work. Dr A. Tan reported receiving personal fees from Amgen and Pfizer outside the submitted work. Dr Lai reported receiving personal fees from Amgen and grants from Merck, Astra Zeneca, Pfizer, Bristol Myers Squibb, and Roche outside the submitted work. Dr D.W.T. Lim reported receiving grants from Bristol Myers Squibb and Boehringer-Ingelheim and personal fees from Merck, Roche, Pfizer, Taiho, and Astra-Zeneca outside the submitted work. Dr Kanesvaran reported receiving personal fees from Merck, Bristol Myers Squibb, Astellas, Johnson & Johnson, Eisai, Ipsen and Novartis outside the submitted work. Dr Ng reported serving on advisory boards for Boehringer Ingelheim and Merck outside the submitted work. Dr W.L. Tan reported receiving personal fees from Amgen, Merck and Novartis outside the submitted work. Dr. Ong reported receiving personal fees from AstraZeneca, MSD and Medtronic, non-financial support from Johnson & Johnson, personal fees and non-financial support from Stryker outside the submitted work. Dr D.S.W. Tan reported grants from AstraZeneca and Amgen and personal fees from Novartis, Boehringer Ingelheim, Bayer, GlaxoSmithKline, Janssen, Amgen, and C4 Therapeutics outside the submitted work. No other disclosures were reported., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Cardiotoxicity leading to heart failure (HF) is a growing problem in many cancer survivors. As specific treatment strategies are not available, RNA discovery pipelines were employed and a new and powerful circular RNA (circRNA)-based therapy was developed for the treatment of doxorubicin-induced HF., Methods and Results: The circRNA sequencing was applied and the highly species-conserved circRNA insulin receptor (Circ-INSR) was identified, which participates in HF processes, including those provoked by cardiotoxic anti-cancer treatments. Chemotherapy-provoked cardiotoxicity leads to the down-regulation of Circ-INSR in rodents and patients, which mechanistically contributes to cardiomyocyte cell death, cardiac dysfunction, and mitochondrial damage. In contrast, Circ-INSR overexpression prevented doxorubicin-mediated cardiotoxicity in both rodent and human cardiomyocytes in vitro and in a mouse model of chronic doxorubicin cardiotoxicity. Breast cancer type 1 susceptibility protein (Brca1) was identified as a regulator of Circ-INSR expression. Detailed transcriptomic and proteomic analyses revealed that Circ-INSR regulates apoptotic and metabolic pathways in cardiomyocytes. Circ-INSR physically interacts with the single-stranded DNA-binding protein (SSBP1) mediating its cardioprotective effects under doxorubicin stress. Importantly, in vitro transcribed and circularized Circ-INSR mimics also protected against doxorubicin-induced cardiotoxicity., Conclusion: Circ-INSR is a highly conserved non-coding RNA which is down-regulated during cardiotoxicity and cardiac remodelling. Adeno-associated virus and circRNA mimics-based Circ-INSR overexpression prevent and reverse doxorubicin-mediated cardiomyocyte death and improve cardiac function. The results of this study highlight a novel and translationally important Circ-INSR-based therapeutic approach for doxorubicin-induced cardiac dysfunction., Competing Interests: Conflict of interest: T.T. is a founder and shareholder of Cardior Pharmaceuticals GmbH (outside the topic of this paper). D.C.L., C.B., and T.T. have filed and partly licensed patents for ncRNAs including one patent for Circ-INSR., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Purpose: HER2 -altered non-small-cell lung cancer (NSCLC) represents a diverse subgroup, including mutations, amplifications, and overexpression. However, HER2 exon 20 insertion mutations are emerging as a distinct molecular subtype with expanding therapeutic options. We describe the molecular epidemiology and genomic features of HER2 -altered NSCLC in an Asian tertiary cancer center., Methods: We identified patients with HER2 -mutated NSCLC in our institutional database, collating clinicopathological features and treatment outcomes. The genomic landscape of human epidermal growth factor receptor 2 ( HER2 )-mutated NSCLC was further evaluated using whole-exome sequencing (WES) data from combined local and publicly available data sets. HER2 amplification and overexpression as selection biomarkers in NSCLC were further interrogated using HER2 immunohistochemistry and correlations with WES and RNA sequencing data., Results: Among 1,252 patients with consecutive lung adenocarcinoma undergoing routine next-generation sequencing, the prevalence of HER2 mutations was 3.1%-exon 20 insertion mutations comprised 2.7%. We examined the clinicopathological features in 55 patients with HER2 -mutated NSCLC comprising 40 exon 20 insertion and 15 nonexon 20 insertion mutations. The most common exon 20 insertion mutation was HER2 Y772&#95;A775dup in 30 (75%), followed by HER2 G776delinsVC in five patients (13%). There were limited responses to HER2-directed therapies apart from trastuzumab-deruxtecan, and no responses were seen with immunotherapy monotherapy. Evaluating the genomics features of HER2 exon 20 insertion mutations using WES data revealed low tumor mutational burden (TMB), low incidence of cancer driver comutations, and a predominance of aging mutational signature-similar to EGFR -mutated tumors. In contrast, uncommon (or nonexon 20 insertion) HER2 -mutated tumors resembled EGFR wild-type tumors with higher TMB, higher frequency of cancer driver comutations, and greater presence of smoking and APOBEC mutational signature. Finally, in evaluating HER2 immunohistochemistry in all lung adenocarcinoma, there was significant discordance comparing different scoring systems and poor correlation with HER2 RNA expression and HER2 amplification., Conclusion: The incidence of HER2 mutations is 3.1% in East Asian nonsquamous NSCLC. HER2 exon 20 insertion-mutated tumors appear genomically distinct from uncommon (nonexon 20 insertion) HER2 mutations, the latter demonstrating higher TMB, co-occurring drivers, and predominant nonaging mutational signature. The therapeutic implications of the genomic and clinical features of HER2 -mutated NSCLC warrant further investigation.

Organic solar cells (OSCs) based on polymer donor and non-fullerene acceptor achieve power conversion efficiency (PCE) more than 19% but their poor absorption below 550 nm restricts the harvesting of high-energy photons. In contrast, wide bandgap all-inorganic perovskites limit the absorption of low-energy photons and cause serious below bandgap loss. Therefore, a 2-terminal (2T) monolithic perovskite/organic tandem solar cell (TSC) incorporating wide bandgap CsPbI 2 Br is demonstrated as front cell absorber and organic PM6:Y6 blend as rear cell absorber, to extend the absorption of OSCs into high-energy photon region. The perovskite sub-cell, featuring a sol-gel prepared ZnO/SnO 2 bilayer electron transporting layer, renders a high open-circuit voltage (V OC ). The V OC is further enhanced by employing thermal annealing (TA)-free process in the fabrication of rear sub-cell, demonstrating a record high V OC of 2.116 V. The TA-free Ag/PFN-Br interface in organic sub-cell facilitates charge transport and restrains nonradiative recombination. Consequently, a remarkable PCE of 20.6% is achieved in monolithic 2T-TSCs configuration, which is higher than that of both reported single junction and tandem OSCs, demonstrating that tandem with wide bandgap all-inorganic perovskite is a promising strategy to improve the efficiency of OSCs., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Introduction: Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC., Methods: This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression. The primary end point was the objective response rate, and the secondary end points included progression-free survival, overall survival, and safety of ICI after EGFR TKI., Results: Recruitment ceased owing to futility after 31 of 184 planned patients were treated. A total of 15 patients received N and 16 received NI combination. There were 16 patients (51.6%) who had programmed death-ligand (PDL1) 1 greater than or equal to 1%, and 15 (45.2%) harbored EGFR T790M. Five patients derived clinical benefits from ICI with one objective response (objective response rate 3.2%), and median progression-free survival was 1.22 months (95% confidence interval: 1.15-1.35) for the overall cohort. None of the four patients who crossed over achieved salvage response by NI. PDL1 and tumor mutational burden (TMB) were not able to predict ICI response. Rates of all grade immune-related adverse events were similar (80% versus 75%), with only two grade 3 events., Conclusions: Immune checkpoint inhibition is ineffective in EGFR TKI-resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients., (© 2022 by the International Association for the Study of Lung Cancer.)

Dengue viruses (DENV) are expanding global pathogens that are transmitted through the bite of mosquitoes, mostly Aedes aegypti. As RNA viruses, DENV rely on RNA-binding proteins (RBPs) to complete their life cycle. Alternatively, RBPs can act as restriction factors that prevent DENV multiplication. While the importance of RBPs is well-supported in humans, there is a dearth of information about their influence on DENV transmission by mosquitoes. Such knowledge could be harnessed to design novel, effective interventions against DENV. Here, we successfully adapted RNA-affinity chromatography coupled with mass spectrometry-a technique initially developed in mammalian cells-to identify RBPs in Ae. aegypti cells. We identified fourteen RBPs interacting with DENV serotype 2 3'UTR, which is involved in the viral multiplication and produces subgenomic flaviviral RNA (sfRNA). We validated the RNA affinity results for two RBPs by confirming that AePur binds the 3'UTR, whereas AeStaufen interacts with both 3'UTR and sfRNA. Using in vivo functional evaluation, we determined that RBPs like AeRan, AeExoRNase, and AeRNase have pro-viral functions, whereas AeGTPase, AeAtu, and AePur have anti-viral functions in mosquitoes. Furthermore, we showed that human and mosquito Pur homologs have a shared affinity to DENV2 RNA, although the anti-viral effect is specific to the mosquito protein. Importantly, we revealed that AeStaufen mediates a reduction of gRNA and sfRNA copies in several mosquito tissues, including the salivary glands and that AeStaufen-mediated sfRNA reduction diminishes the concentration of transmission-enhancing sfRNA in saliva, thereby revealing AeStaufen's role in DENV transmission. By characterizing the first RBPs that associate with DENV2 3'UTR in mosquitoes, our study unravels new pro- and anti-viral targets for the design of novel therapeutic interventions as well as provides foundation for studying the role of RBPs in virus-vector interactions., Competing Interests: The authors have declared that no competing interests exist.

Atopic dermatitis (AD) is a chronic and pruritic skin inflammatory disease causing a significant burden to health care management and patient's quality of life. Seemingly healthy skin or non-lesional sites on AD patients still presents skin barrier defects and immune response, which can develop to AD at a later stage. To investigate further the balance between the epidermal barrier impairment and intrinsic immune dysregulation in AD, we exploited multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) to image lesional and non-lesional skin areas on AD patients of different severities non-invasively to elucidate their structural features and functional information. Herein, we demonstrate the objective assessment of AD severity using relative changes in oxygen saturation (δsO 2 ) levels in microvasculature along with other structural parameters such as relative changes in epidermis thickness (δET) and total blood volume (δTBV) between the lesional and non-lesional areas of the skin. We could observe an increasing trend for δsO 2 and δTBV, which correlated well with the subjective clinical Scoring Atopic Dermatitis (SCORAD) for evaluating the severity. Notably, δET showed a decreasing trend with AD severity, indicating that the difference in epidermal thickness between lesional and non-lesional area of the skin decreases with AD severity. Our results also correlated well with conventional metrics such as trans-epidermal water loss (TEWL) and erythrosine sedimentation rate (ESR). We quantified the δsO 2 and δET changes to objectively evaluate the treatment response before and four months after treatment using topical steroids and cyclosporine in one severe AD patient. We observed reduced δsO 2 and δET post treatment. We envision that in future, functional and structural imaging metrics derived from ms-RSOM can be translated as objective markers to assess and stratify the severity of AD and understand the function of skin barrier dysfunctions and immune dysregulation. It could also be employed to monitor the treatment response of AD in regular clinical settings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier GmbH.)

Double-cable conjugated polymers with near-infrared (NIR) electron acceptors are synthesized for use in single-component organic solar cells (SCOSCs). Through the development of a judicious synthetic pathway, the highly sensitive nature of the 2-(3-oxo-2,3-dihydroinden-1-ylidene)malononitrile (IC)-based electron acceptors in basic and protonic solvents is overcome. In addition, an asymmetric design motif is adopted to optimize the packing of donor and acceptor segments, enhancing charge separation efficiency. As such, the new double-cable polymers are successfully applied in SCOSCs, providing an efficiency of over 10 % with a broad photo response from 300 to 850 nm and exhibiting excellent thermal/light stability. These results demonstrate the powerful design of NIR-acceptor-based double-cable polymers and will enable SCOSCs to enter a new stage., (© 2022 Wiley-VCH GmbH.)

The development of human-induced pluripotent stem cell-derived cardiac cell types has created a new paradigm in assessing drug-induced cardiotoxicity. Advances in genomics and epigenomics have also implicated several genomic loci and biological pathways that may contribute to susceptibility to cancer therapies. In this review, we first provide a brief overview of the cardiotoxicity associated with chemotherapy. We then provide a detailed summary of systems biology approaches being applied to elucidate potential molecular mechanisms involved in cardiotoxicity. Finally, we discuss combining systems biology approaches with iPSC technology to help discover molecular mechanisms associated with cardiotoxicity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The way in which conjugated polymers pack in the solid state strongly affects the performance of polymer-based optoelectronic devices. However, even for the most crystalline conjugated polymers the precise packing of chains within the unit cell is not well established. Here we show that by performing resonant X-ray diffraction experiments at the sulfur K-edge we are able to resolve the tilting of the planar backbones of crystalline poly(3-hexylthiophene) (P3HT) within the unit cell. This approach exploits the anisotropic nature of the X-ray optical properties of conjugated polymers, enabling us to discern between different proposed crystal structures. By comparing our data with simulations based on different orientations, a tilting of the planar conjugated backbone with respect to the side chain stacking direction of 30 ± 5° is determined.

Salmonella Enteritidis is a major foodborne pathogen worldwide. In this study, a total of 276 S. enteritidis isolates, collected between 2016 and 2017 from human, food and farm/slaughterhouse samples, were studied to enhance the understanding of the epidemiology of human salmonellosis in Singapore. Results showed all 276 isolates belonged either to ST1925 (70.3%) or ST11 (29.7%), with ST11 being significantly more frequent in extra-intestinal isolates and chicken isolates. Food isolates, most of which were from poultry, showed the highest prevalence of resistance (33-37%) against beta-lactams or beta-lactams/beta-lactamase inhibitor combination (ampicillin, piperacillin and ampicillin/sulbactam). The analysis showed the detection of genes associated with resistance to aminoglycoside genes (99.6%), tetracycline (55.1%), and beta-lactams (14.9%) of all isolates. Nine types of plasmids were found in 266 isolates; the most common incompatibility group profiles were IncFIB(S)-IncFII(S)-IncX1 (72.2%) and IncFIB(S)-IncFII(S) (15.8%). Most plasmid harbouring isolates from chicken (63.6%, 14/22) and from human (73.8%, 175/237) shared the same plasmid profile (IncFIB(S)-IncFII(S)-IncX1). SNP analysis showed clustering of several isolates from poultry food products and human isolates, suggesting phylogenetic relatedness among these isolates. Lastly, this study provides important epidemiological insights on the application of phenotypic and next-generation sequencing (NGS) tools for improved food safety and public health surveillance and outbreak investigation of S. enteritidis .

Circular RNAs (circRNAs) are a new and large group of non-coding RNA molecules that are abundantly expressed in the central nervous system. However, very little is known about their roles in traumatic brain injury. In this study, we firstly screened differentially expressed circRNAs in normal and injured brain tissues of mice after traumatic brain injury. We found that the expression of circLphn3 was substantially decreased in mouse models of traumatic brain injury and in hemin-treated bEnd.3 (mouse brain cell line) cells. After overexpressing circLphn3 in bEnd.3 cells, the expression of the tight junction proteins, ZO-1, ZO-2, and occludin, was upregulated, and the expression of miR-185-5p was decreased. In bEnd.3 cells transfected with miR-185-5p mimics, the expression of ZO-1 was decreased. Dual-luciferase reporter assays showed that circLphn3 bound to miR-185-5p, and that miR-185-5p bound to ZO-1. Additionally, circLphn3 overexpression attenuated the hemin-induced high permeability of the in vitro bEnd.3 cell model of the blood-brain barrier, while miR-185-5p transfection increased the permeability. These findings suggest that circLphn3, as a molecular sponge of miR-185-5p, regulates tight junction proteins' expression after traumatic brain injury, and it thereby improves the permeability of the blood-brain barrier. This study was approved by the Animal Care and Use Committee of Chongqing Medical University of China (approval No. 2021-177) on March 22, 2021., Competing Interests: None

Background: Hantaviruses (HVs) are major zoonotic pathogens in China that cause hemorrhagic fever with renal syndrome (HFRS) posing a major threat to people's health. Hainan Province, an island located in Southeast China, is an ideal region for sea ports. The unique tropical monsoon climate in Hainan provides sufficient living conditions for rodents, which help spread HVs and other rodent-borne diseases. In the routine monitoring of hantavirus, there was no evidence that rodents in Hainan carried hantavirus. No patients infected with hantavirus were found in the past. However, the surveillance of HVs-carrying rodents covering the whole territory of Hainan has not stopped., Methodology/principal Findings: For the monitoring of the prevalence of HVs in rodents and the search for theoretical reference for rodent control and HFRS prevention, a total of 60 rodents from 6 monitoring spots were trapped around main ports in Hainan between 2016 and 2019. HV positive samples were identified by a specific kit and sequenced. The data indicated that seven rodents (Rattus norvegicus) were positive for hantavirus with a positivity rate of 11.67%. Phylogenetic analysis suggested that the two complete sequence strains HN1 and HN4 in this research were highly similar to the sequence strains GZRn36 and GZRn148 isolated in Guangdong Province, and they located in the same phylogenetic tree branch which belongs to S2 subtype. Although the two partial sequences HT1 and HT2 isolated in Xisha Islands belong to S2 subtype according to the phylogenetic tree of L segment, they showed a great nucleotide difference with HN1 and HN4. We also found 13 amino acid variations compared with SEOV 80-39 and 6 amino acid mutations related to epitope, and the variations may reduce the effectiveness of the current HFRS vaccines used in humans., Conclusions/significance: The study indicated HVs carried by rodents found in Hainan Province may be transmitted from Guangdong Province through trading ports and carriage of goods by sea. So it is of great significance to strengthen the surveillance of rodents in port areas especially capture and eliminate rodents on ship. Timely elimination of host animals of hantavirus in port areas is necessary to prevent an outbreak of HVs disease., Competing Interests: All the authors declared no competing interests.

Rapid onsite whole-genome sequencing of two suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene diagnostic escape samples revealed a previously unreported N gene point mutation at genome position 29195. Because the G29195T mutation occurs within a region probed by a commonly referenced U.S. CDC N gene reverse transcription (RT)-PCR assay, we hypothesize that the G29195T mutation rendered the N gene target of a proprietary commercial assay undetectable. The putative diagnostic escape G29195T mutation demonstrates the need for nearly real-time surveillance, as emergence of a novel SARS-CoV-2 variant with the potential to escape diagnostic tests continues to be a threat. IMPORTANCE Accurate diagnostic detection of SARS-CoV-2 currently depends on the large-scale deployment of RT-PCR assays. SARS-CoV-2 RT-PCR assays target predetermined regions in the viral genomes by complementary binding of primers and probes to nucleic acid sequences in the clinical samples. Potential diagnostic escapes, such as those of clinical samples harboring the G29195T mutation, may result in false-negative SARS-CoV-2 RT-PCR results. The rapid detection and sharing of potential diagnostic escapes are essential for diagnostic laboratories and manufacturers around the world, to optimize their assays as SARS-CoV-2 continues to evolve.

Background and Aims: Despite the remarkable progress of metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the disease remains poorly improved. Since increased oxidative stress and inflammation contribute to the initiation and progression of fatty liver disorders, vitamin C (VC), an antioxidant agent, might be a suitable treatment option for MAFLD. However, the lack of clinically confirmed benefits makes clinicians challenging to recommend antioxidant supplements for MAFLD individuals., Methods: Herein, the nationally representative National Health and Nutrition Examination Survey 2017-2018 data were collected to evaluate the potential association between the serum VC levels with the risk of different categories of NALFD and the newly proposed MAFLD terminology. Hepatic steatosis was defined as controlled attenuated parameter scores ≥ 263 dB/m, whereas liver fibrosis (LF) status was defined as F0-F4, with the cutoff values of median liver stiffness being 6.3, 8.3, 10.5, and 12.5 (KPa), respectively. A cross-sectional analysis was performed to calculate the odds rate and determine the potential beneficial effects of VC., Results: A total of 4,494 participants aged more than 18 years and conducted transient elastography examinations were included. Our findings demonstrated that participants with increased serum VC status were more likely to be female predominant, more educated, and moderate drinkers. Interestingly, female participants tended to have a lower prevalence of NAFLD, MAFLD, LF, and liver cirrhosis (LC) after stratification by gender. Moreover, our results revealed that participants from the quartile three group (quartile 3: 50.5-67.0 μmol/L) experienced a slightly lower risk of MAFLD than the risk of NAFLD. Of note, the serum concentration of VC (quartile 2: 30.9-50.5 μmol/L) inversely associated with LF and LC was lower than the serum VC level (quartile 3) associated with NAFLD and MAFLD. Notably, individuals from the quartile 3 group experienced a statistically significant 32.5, 42.0, 45.7, and 71% decrease in risk of NAFLD, MAFLD, LF, and LC, respectively., Conclusion: In summary, our findings suggested an inverse association between serum VC levels and NAFLD, MAFLD, LF, or LC. Additionally, adjustment of VC supplementation according to age, gender, and ethnicity may be a promising candidate for these diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Li, Tan, Yang, Ma, Li, Wang, Shang and Chen.)

Forty samples of optically active falcarindiol analogues are synthesized by using the easily available C2 symmetric (R)- and (S)-1,1'-binaphth-2-ol (BINOL) in combination with Ti(O i Pr) 4 , Zn powder and EtI. Their anticancer activities on Hccc-9810, HepG2, MDA-MB-231, Hela, MG-63 and H460 cells are assayed to elucidate their structure-activity relationships. These results showed that the falcarindiol analogue (3R,8S)-2 i with the terminal double bond has the most potent anti-proliferation effect on Hccc-9810 cells with IC 50 value of 0.46 μM. The falcarindiol analogue (3R,8S)-2 i can induce obvious Hccc-9810 cell apoptosis in a concentration-dependent manner by Hoechst staining and flow cytometry analysis. The proposed mechanism suggests that the falcarindiol analogue (3R,8S)-2 i increases LDH release and MDA content, and reduces the levels of SOD activity, which lead to the accumulation of oxidative stress and induce apoptosis in Hccc-9810 cells., (© 2021 Wiley-VCH GmbH.)