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Rich and diverse fungal species occur in different habitats on the earth. Many new taxa are being reported and described in increasing numbers with the advent of molecular phylogenetics. However, there are still a number of unknown fungi that have not yet been discovered and described. During a survey of fungal diversity in different habitats in China, we identified and proposed two new species, based on the morphology and multi-gene phylogenetic analyses. Herein, we report the descriptions, illustrations and molecular phylogeny of the two new species, Bisifusariumkeratinophilum sp. nov. and Ovatosporasinensis sp. nov., Competing Interests: The authors have declared that no competing interests exist., (Hai-Yan Wang, Xin Li, Chun-Bo Dong, Yan-Wei Zhang, Wan-Hao Chen, Jian-Dong Liang, Yan-Feng Han.)

Using bone char for contaminated wastewater treatment and soil remediation is an intriguing approach to environmental management and an environmentally friendly way of recycling waste. The bone char remediation strategy for heavy metal-polluted wastewater was primarily affected by bone char characteristics, factors of solution, and heavy metal (HM) chemistry. Therefore, the optimal parameters of HM sorption by bone char depend on the research being performed. Regarding enhancing HM immobilization by bone char, a generic strategy for determining optimal parameters and predicting outcomes is crucial. The primary objective of this research was to employ artificial neural network (ANN) technology to determine the optimal parameters via sensitivity analysis and to predict objective function through simulation. Sensitivity analysis found that for multi-metals sorption (Cd, Ni, and Zn), the order of significance for pyrolysis parameters was reaction temperature > heating rate > residence time. The primary variables for single metal sorption were solution pH, HM concentration, and pyrolysis temperature. Regarding binary sorption, the incubation parameters were evaluated in the following order: HM concentrations > solution pH > bone char mass > incubation duration. This approach can be used for further experiment design and improve the immobilization of HM by bone char for water remediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Background/aim: Chronic lymphocytic leukemia is a slowly-progressing disease in which symptoms often do not manifest until years after disease onset. In advanced stages, infection and bleeding are common. Past studies have shown that the interaction between CDK4/6 inhibitors and chemotherapy drugs can enhance the anti-tumor efficacy of drugs and limit toxicity. Therefore, in this study, the treatment effects of combining the CDK4/6 inhibitor LEE011 with chemotherapy drugs bendamustine or hydroxyurea were investigated in vitro., Materials and Methods: The mouse lymphocytic leukemia cell line L1210 was treated with LEE011 combined with hydroxyurea or bendamustine. Western blot and flow cytometry were performed to elucidate the mechanisms behind tumor suppression., Results: LEE011 combined with hydroxyurea or bendamustine significantly inhibited proliferation of L1210 cell lines in a concentration- and time-dependent manner as well as increased the arrest of cells in G 1 and S phases. The combination of LEE011 with hydroxyurea also reduced the phosphorylation of Rb while increased the expression of total Rb protein. Furthermore, reduced expression of GPX4, which is a key protein in ferroptosis, indicates that the tumor suppression effects of this drug combination could involve ferroptosis., Conclusion: CDK4/6 inhibitor LEE011 treatment alone may not be a suitable treatment option for lymphocytic leukemia; however, our findings in vitro support the combination of LEE011 with chemotherapy drugs to enhance anti-tumor activity in lymphocytic leukemia., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: The integration of artificial intelligence (AI) and machine learning (ML) in health care to aid clinical decisions is widespread. However, as AI and ML take important roles in health care, there are concerns about AI and ML associated fairness and bias. That is, an AI tool may have a disparate impact, with its benefits and drawbacks unevenly distributed across societal strata and subpopulations, potentially exacerbating existing health inequities. Thus, the objectives of this scoping review were to summarize existing literature and identify gaps in the topic of tackling algorithmic bias and optimizing fairness in AI/ML models using real-world data (RWD) in health care domains., Methods: We conducted a thorough review of techniques for assessing and optimizing AI/ML model fairness in health care when using RWD in health care domains. The focus lies on appraising different quantification metrics for accessing fairness, publicly accessible datasets for ML fairness research, and bias mitigation approaches., Results: We identified 11 papers that are focused on optimizing model fairness in health care applications. The current research on mitigating bias issues in RWD is limited, both in terms of disease variety and health care applications, as well as the accessibility of public datasets for ML fairness research. Existing studies often indicate positive outcomes when using pre-processing techniques to address algorithmic bias. There remain unresolved questions within the field that require further research, which includes pinpointing the root causes of bias in ML models, broadening fairness research in AI/ML with the use of RWD and exploring its implications in healthcare settings, and evaluating and addressing bias in multi-modal data., Conclusion: This paper provides useful reference material and insights to researchers regarding AI/ML fairness in real-world health care data and reveals the gaps in the field. Fair AI/ML in health care is a burgeoning field that requires a heightened research focus to cover diverse applications and different types of RWD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guo received research funding from PhRMA foundation and received consulting fee from Pfizer, outside the current work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Trilobolide-6-O-isobutyrate exhibits significant antitumor effects on cholangiocarcinoma (CCA) cells by effectively inhibiting the JAK/STAT3 signaling pathway. This study aims to investigate the mechanisms underlying the antitumor properties of trilobolide-6-O-isobutyrate, and to explore its potential as a therapeutic agent for CCA. This study illustrates that trilobolide-6-O-isobutyrate efficiently suppresses CCA cell proliferation in a dose- and time-dependent manner. Furthermore, trilobolide-6-O-isobutyrate stimulates the production of reactive oxygen species, leading to oxidative stress and initiation of apoptosis via the activation of the mitochondrial pathway. Data from xenograft tumor assays in nude mice confirms that TBB inhibits tumor growth, and that there are no obvious toxic effects or side effects in vivo . Mechanistically, trilobolide-6-O-isobutyrate exerts antitumor effects by inhibiting STAT3 transcriptional activation, reducing PCNA and Bcl-2 expression, and increasing P21 expression. These findings emphasizes the potential of trilobolide-6-O-isobutyrate as a promising therapeutic candidate for the treatment of CCA., 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., (© 2024 The Authors.)

Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55-90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187-3.051) for TG/HDL-C, 1.975 (95% CI: 1.188-3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113-3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003-1.030) and 0.926 (95% CI: 0.876-0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations.

Background: Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown., Methods: We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays., Results: We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group., Conclusions: Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens., Clinical Trials Registration: NCT03738241., Competing Interests: Potential conflicts of interest . I. Y.’s institution received funding to conduct clinical research unrelated to this manuscript from Moderna and Pfizer; and I. Y. consults for Merck and Sanofi-Pasteur. P. W. has received research funding unrelated to this manuscript from Pfizer and Sanofi; and has consulted for Pfizer. C. B. C. serves as a consultant to Pfizer, Moderna, GSK, and Vir. K. M. E. serves as consultant to Bionet and IBM; and member of the Data Safety and Monitoring Boards for Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, and Roche. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient reported outcomes (PRO) to determine RA status and severity in a study of 30 moderate-to-severe RA patients, compared to 30 matched healthy controls (HC). Sensor-based measures of health status, mobility, dexterity, fatigue, and other RA specific symptoms were extracted from daily iPhone guided tests (GT), as well as actigraphy and heart rate sensor data, which was passively recorded from patients' Apple smartwatch continuously over the study duration. We subsequently developed a machine learning (ML) framework to distinguish RA status and to estimate RA severity. It was found that daily wearable sensor-outcomes robustly distinguished RA from HC participants (F1, 0.807). Furthermore, by day 7 of the study (half-way), a sufficient volume of data had been collected to reliably capture the characteristics of RA participants. In addition, we observed that the detection of RA severity levels could be improved by augmenting standard patient reported outcomes with sensor-based features (F1, 0.833) in comparison to using PRO assessments alone (F1, 0.759), and that the combination of modalities could reliability measure continuous RA severity, as determined by the clinician-assessed RAPID-3 score at baseline (r 2 , 0.692; RMSE, 1.33). The ability to measure the impact of the disease during daily life-through objective and remote digital outcomes-paves the way forward to enable the development of more patient-centric and personalised measurements for use in RA clinical trials., (© 2024. The Author(s).)

This research successfully developed an independent Ge-based VCSEL epitaxy and fabrication technology route, which set the stage for integrating AlGaAs-based semiconductor devices on bulk Ge substrates. This is the second successful Ge-based VCSEL technology reported worldwide and the first Ge-based VCSEL technology with key details disclosed, including Ge substrate specification, transition layer structure and composition, and fabrication process. Compared with the GaAs counterparts, after epitaxy optimization, the Ge-based VCSEL wafer has a 40% lower surface root-mean-square roughness and 72% lower average bow-warp. After device fabrication, the Ge-based VCSEL has a 10% lower threshold current density and 19% higher maximum optical differential efficiency than the GaAs-based VCSEL.

Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance. In Huh7 cells, treatment with apigenin decreased the mRNA expression of fetuin-A by decreasing reactive oxygen species-mediated casein kinase 2α (CK2α)-nuclear factor kappa-light-chain-enhancer of activated B activation; besides, apigenin decreased the levels of CK2α-dependent fetuin-A phosphorylation and thus promoted fetuin-A degradation through the autophagic pathway, resulting in a decrease in the protein levels of fetuin-A. Moreover, apigenin prevented the formation of the fetuin-A-insulin receptor (IR) complex and thereby rescued the PA-induced impairment of the insulin signaling pathway, as evidenced by increased phosphorylation of IR substrate-1 and Akt, and translocation of glucose transporter 2 from the cytosol to the plasma membrane. Similar results were observed in the liver of HFD-fed mice treated with apigenin. Collectively, our findings revealed that apigenin ameliorates obesity-induced insulin resistance in the liver by targeting fetuin-A., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Lyme disease, caused by Lyme Borrelia spirochetes, is the most common vector-borne illness in the United States. Despite its global significance, with an estimated 14.5 % seroprevalence, there is currently no licensed vaccine. Previously, we demonstrated that CspZ-YA protein conferred protection against Lyme Borrelia infection, making it a promising vaccine candidate. However, such a protein was tagged with hexahistidine, and thus not preferred for vaccine development; furthermore, the formulation to stabilize the protein was understudied. In this work, we developed a two-step purification process for tag-free E. coli-expressed recombinant CspZ-YA. We further utilized various bioassays to analyze the protein and determine the suitable buffer system for long-term storage and formulation as a vaccine immunogen. The results indicated that a buffer with a pH between 6.5 and 8.5 stabilized CspZ-YA by reducing its surface hydrophobicity and colloidal interactions. Additionally, low pH values induced a change in local spatial conformation and resulted in a decrease in α-helix content. Lastly, an optimal salinity of 22-400 mM at pH 7.5 was found to be important for its stability. Collectively, this study provides a fundamental biochemical and biophysical understanding and insights into the ideal stabilizing conditions to produce CspZ-YA recombinant protein for use in vaccine formulation and development., Competing Interests: Declaration of competing interest JL, ZL, US, MEB, and WHC are co-inventors and/or patent holders of several vaccine technologies against neglected tropical and/or other emerging diseases owned by Baylor College of Medicine (BCM); nothing to report. YPL is the Co-inventor and patent holder for CspZ-YA molecules (patent number US20220280627A1) owned by the New York State Department of Health (NYSDH). All authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Exposed rock masses in tunnel portals are susceptible to thermal deterioration in southern China, where temperatures are relatively high. The thermal stress field of rock masses is affected by fracture shape and distribution as fractures near the surface are channels for solar radiation energy to be converted into rock thermal energy. In this study, a function expression is developed for triangular heat sources of fractured rock masses in a tunnel portal in a high-temperature environment. By the function expression, the temperature field and thermal stress field are calculated, and the influence of fracture shape parameters and multi-fracture interaction is analyzed. The results are as follows: (1) the temperature field and thermal stress field of exposed rocks are redistributed by fractures. The internal temperature of the fractured rocks is higher than that of non-fractured rocks, and thermal stress near the fracture tip increases. (2) For triangular fractures of the same length, thermal stress increases as the apex angle increases. (3) When the spacing between parallel fractures or coplanar fractures is close, the superposition effect of thermal stress becomes significant. (4) In a high-temperature environment, temperature field and thermal stress field of a fractured rock are both nonlinear as temperature and thermal stress around fractures increase significantly. The results provide effective reference for stability evaluation of fractured rock masses in tunnel portals and offer theoretical foundation for thermal diseases analysis and protection measures of tunnel engineering in high-temperature environments of southern China., (© 2024. The Author(s).)

Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitope, and WRAIR-2123, the class I ACE2-binding site. The broad reactivity of class IV and V mAbs to conserved regions of SARS-CoV-2 VoCs and other sarbecovirus provides a framework for long-term immunotherapeutic development strategies., Competing Interests: Declaration of interests Patent application number PCT/US 63/140,763 was filed containing mAbs described in this publication for authors S.J.K., K.M., V.D., S.M.T., G.D., and N.L.M. The status of the patent is pending, not yet published. M.G.J. and K.M. are named as inventors on International Patent Application No. WO 2021/178971 A1 entitled “Vaccines against SARS-CoV-2 and other coronaviruses.” M.G.J. is named as an inventor on International Patent Application No. WO/2018/081318 and U.S. patent 10,960,070 entitled “Prefusion Coronavirus S Proteins and Their Use.”, (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the impact of repeated dilatation and curettage or hysteroscopic biopsy on fetomaternal outcomes in patients receiving progestin treatment for endometrial hyperplasia or early-stage carcinoma., Method: This was a population-based study using the Taiwan National Health Insurance Research Database between 2009 and 2017 of women who gave birth and had a history of endometrial hyperplasia and early-stage carcinoma treated with progestins. Logistic regression analysis was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) reflecting the association between repeated procedures and fetomaternal outcomes., Results: A total of 6956 women with 8690 deliveries were identified. Compared with those who had two or fewer procedures, women who received more than two procedures had a significantly higher risk for cervical insufficiency (aOR, 5.09 [95 CI, 2.31-11.24]). Furthermore, women who had more than two procedures were prone to have adverse neonatal outcomes, including Apgar score < 7 at 1 min (aOR, 1.97 [95% CI, 1.13-3.43]) and 5 min (aOR, 3.11 [95% CI, 1.33-7.23]) and preterm delivery <32 weeks (aOR, 2.86 [95% CI, 1.50-5.45])., Conclusion: Undergoing more than two procedures was associated with subsequent maternal cervical insufficiency, preterm delivery <32 weeks, and low neonatal Apgar score. Health care providers should be aware of the potential risks and balance the benefits and harms of repeated procedures., (© 2023 International Federation of Gynecology and Obstetrics.)

In this Letter, we present a comprehensive analysis of the high-speed performance of 940 nm oxide-confined AlGaAs vertical-cavity surface-emitting lasers (VCSELs) grown on Ge substrates. Our demonstration reveals a pronounced superiority of Ge-based VCSELs in terms of thermal stability. The presented Ge-VCSEL has a maximum modulation bandwidth of 16.1 GHz and successfully realizes a 25 Gb/s NRZ transmission at 85  ∘ C. The experimental results underscore the significance and potential of Ge-VCSELs for applications requiring robust performance in high-temperature environments, laying the cornerstone for the future development of VCSEL devices.

Purpose: This qualitative study (GSK study: 213635) was designed to better understand sleep disturbance as experienced by individuals with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA), and the relationship between sleep disturbance and pain and other aspects of the disease and disease activity., Methods: Sixty-minute, one-on-one, concept elicitation interviews were conducted with 30 participants (15 with RA and 15 with axSpA) from the US. Interviews were audio-recorded and transcribed verbatim. Interview transcripts were coded and analyzed to explore themes related to pain and sleep disturbance, and relationships among those themes., Results: Pain was a prominent driver of sleep disturbance; 12 participants with RA (80%) and 14 with axSpA (93%) reported that pain impacted their ability to fall asleep, while all 15 with RA (100%) and 14 with axSpA (93%) reported that pain impacted their ability to stay asleep. Two-thirds of participants with RA (67%) or axSpA (60%) described a bi-directional relationship, whereby pain worsened sleep disturbance and sleep disturbance further aggravated pain. Factors other than pain, such as fatigue and emotional health, were also reported as important contributors to sleep disturbance (RA: n = 12/15, 80%; axSpA: n = 14/15, 93%). Participants with RA or axSpA described complex interconnections between fatigue, emotional health, pain, and sleep, often labeling these relationships as "vicious cycles". Notably, half of all participants reported sleep disturbance occurring without pain or other understood causes., Conclusion: These perspectives collected from people with RA or axSpA suggest that reducing sleep disruption directly may offer clinically relevant benefits., (© 2023. The Author(s).)

Many aspects of Controlled Human Infection Models (CHIMs, also known as human challenge studies and human infection studies) have been discussed extensively, including Good Manufacturing Practice (GMP) production of the challenge agent, CHIM ethics, environmental safety in CHIM, recruitment, community engagement, advertising and incentives, pre-existing immunity, and clinical, immunological, and microbiological endpoints. The fourth CHIM meeting focused on regulation of CHIM studies, bringing together scientists and regulators from high-, middle-, and low-income countries, to discuss barriers and hurdles in CHIM regulation. Valuable initiatives for regulation of CHIMs have already been undertaken but further capacity building remains essential. The Wellcome Considerations document is a good starting point for further discussions., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A, are widely used to treat hypercholesterolemia. In addition, statins have been suggested to reduce the risk of cardiovascular events owing to their pleiotropic effects on the vascular system, including vasodilation, anti-inflammation, anti-coagulation, anti-oxidation, and inhibition of vascular smooth muscle cell proliferation. The major beneficial effect of statins in maintaining vascular homeostasis is the induction of nitric oxide (NO) bioavailability by activating endothelial NO synthase (eNOS) in endothelial cells. The mechanisms underlying the increased NO bioavailability and eNOS activation by statins have been well-established in various fields, including transcriptional and post-transcriptional regulation, kinase-dependent phosphorylation and protein-protein interactions. However, the mechanism by which statins affect the metabolism of L-arginine, a precursor of NO biosynthesis, has rarely been discussed. Autophagy, which is crucial for energy homeostasis, regulates endothelial functions, including NO production and angiogenesis, and is a potential therapeutic target for cardiovascular diseases. In this review, in addition to summarizing the molecular mechanisms underlying increased NO bioavailability and eNOS activation by statins, we also discuss the effects of statins on the metabolism of L-arginine., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation in the disparities in initiating these medications., Methods: Using 2017-2018 claims data from a 15% random nationwide sample of Medicare Part D beneficiaries, we identified individuals diagnosed with type 2 diabetes (T2D), who had ≥1 GLD prescriptions, and did not use SGLT2i or GLP1a in the year prior to the index date,1/1/2018. Patients were followed up for a year. The cohort was spatiotemporally linked to Dartmouth hospital-referral regions (HRRs), with each patient assigned to 1 of 306 HRRs. We performed multivariable Poisson regression to estimate adjusted initiation rates, and multivariable logistic regression to assess racial disparities in each HRR., Results: Among 795,469 individuals with T2D included in the analyses, the mean (SD) age was 73 (10) y, 53.3% were women, 12.2% were non-Hispanic Black, and 7.2% initiated a newer GLD in the follow-up year. In the adjusted model including clinical factors, compared to non-Hispanic White patients, non-Hispanic Black (initiation rate ratio, IRR [95% CI]: 0.66 [0.64-0.68]), American Indian/Alaska Native (0.74 [0.66-0.82]), Hispanic (0.85 [0.82-0.87]), and Asian/Pacific islander (0.94 [0.89-0.98]) patients were less likely to initiate newer GLDs. Significant geographic variation was observed across HRRs, with an initiation rate spanning 2.7%-13.6%., Conclusions: This study uncovered substantial geographic variation and the racial disparities in initiating newer GLDs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen 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.)

Background: Interpretation thresholds for patient-reported outcome (PRO) scores are of crucial importance, particularly when interpreting treatment benefit. This study was designed to determine the within-patient meaningful improvement (WPMI) thresholds for the Short-Form 36 Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and the novel Rheumatoid Arthritis Symptoms and Impact Questionnaire (RASIQ) among patients with rheumatoid arthritis (RA)., Methods: In this post-hoc analysis, anchor-based and supportive distribution-based methods were used to derive WPMI based on blinded data from all treatment arms in two Phase 2 RA trials with otilimab. Patient's Global Assessment of Disease Activity (PtGA) was the general anchor for all SF-36v2 scales. SF-36 Patient's Global Impression of Status (PGIS), PtGA, and VT03 (an SF-36v2 item) were used as anchors for FACIT-Fatigue. SF-36 PGIS, PtGA, and Patient's Assessment of Arthritis Pain (PAIN) were anchors for RASIQ. Mean change was calculated for the anchor category associated with minimal meaningful improvement from baseline to Week 24 for SF-36v2 and FACIT-Fatigue, and to Week 12 for RASIQ. Sensitivity and specificity were used to evaluate the accuracy of estimated WPMI values., Results: For the SF-36v2 physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health domains, anchor-based estimates of WPMI based on 0-100 scores were 24.5, 24.5, 25.4, 13.6, 21.5, 20.5, 16.9, and 14.3, respectively. Anchor-based WPMI estimates were 9.7 for the Physical Component Summary score and 7.6 for the Mental Component Summary score (using norm-based T-score metric). For FACIT-Fatigue (range 0-52), WPMI estimates ranged from 9.7 to 11.3 points. For RASIQ (range 0-100), anchor-based WPMI was determined as a change between -32.7 and -21.7 points for the Joint Pain scale, -26.7 to -23.7 for the Joint Stiffness scale, and -21.1 to -17.4 for the Impact scale., Conclusions: This study derived WPMI thresholds for SF-36v2, FACIT-Fatigue, and RASIQ among patients with RA, using multiple anchors. Derivation of WPMI thresholds for these PRO instruments will enable their broader use in evaluating and interpreting treatment benefit in future RA studies., (© 2024. The Author(s).)

Transition metal dichalcogenides, by virtue of their two-dimensional structures, could provide the largest active surface for reactions with minimal materials consumed, which has long been pursued in the design of ideal catalysts. Nevertheless, their structurally perfect basal planes are typically inert; their surface defects, such as under-coordinated atoms at the surfaces or edges, can instead serve as catalytically active centers. Here we show a reaction probability > 90 % for adsorbed methanol (CH 3 OH) on under-coordinated Pt sites at surface Te vacancies, produced with Ar + bombardment, on layered PtTe 2 - approximately 60 % of the methanol decompose to surface intermediates CH x O (x = 2, 3) and 35 % to CH x (x = 1, 2), and an ultimate production of gaseous molecular hydrogen, methane, water and formaldehyde. The characteristic reactivity is attributed to both the triangular positioning and varied degrees of oxidation of the under-coordinated Pt at Te vacancies., (© 2024. The Author(s).)

Background: This study evaluates the impact of hybrid dynamic stabilization using the Dynesys-Transition-Optima (DTO) system on adjacent segment disease (ASD) in lumbar spinal stenosis patients with spondylolisthesis., Methods: From 2012 to 2020, 115 patients underwent DTO stabilization at a single center by a single neurosurgeon. After exclusions for lack of specific stabilization and incomplete data, 31 patients were analyzed. Follow-up was conducted at 6, 12, and 24 months postoperatively, assessing disc height, listhesis distance, and angular motion changes at L2-L3, L3-L4, and L5-S1., Results: L3-L4 segment (the index level), demonstrated a delayed increase in listhesis distance, contrasting with earlier changes in other segments. At two years, L3-L4 exhibited less increase in listhesis distance and less disc height reduction compared to L2-L3 and L5-S1. Notably, the L3-L4 segment showed a significant reduction in angular motion change over two years., Conclusions: In conclusion, while ASD was not significantly prevented, the study indicates minor and delayed degeneration at the index level. The L3-L4 segment experienced reduced angular change in motion, suggesting a potential benefit of DTO in stabilizing this specific segment.

Wood boards used in construction are generally treated with toxic chemicals, making them unsuitable for further use and causing environmental pollution. This study evaluates the possibility of using catalytic torrefaction as a pretreatment to improve wood pyrolysis and combustion for greener biochar production. Waste beech boards were impregnated with different K 2 CO 3 solutions (0-0.012 M), then torrefied between 5 and 60 min at 275 °C. The ICP-AES showed that the board's surface held more potassium than the core. Torrefaction coupled with potassium decreased the C-O and -OH stretches. Thermogravimetric analysis of torrefied wood showed that the board's internal heating degraded the core more than the surface. The exothermic reactions made potassium's catalytic action more efficient in the core. Interactions between the potassium content and torrefaction duration decreased the pyrolysis' maximum devolatilization temperature. During combustion, potassium decreased the ignition temperature by up to 9% and 3% at the surface and core, respectively, while the torrefaction increased it. The catalytic torrefaction significantly decreased the devolatilization peak during combustion, thus making the wood's combustion similar to that of coal, having only the char oxidation step. These findings highlight the advantages and challenges of waste wood's catalytic-torrefaction for biochar production to reduce environmental pollution., 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 Elsevier Ltd. All rights reserved.)

Background: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage viruses, which differed antigenically from those of earlier waves, predominated., Methods: In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.75, 7.5, and 15 µg of hemagglutinin (HA) with AS03A adjuvant and at doses of 15 and 45 µg of HA without adjuvant., Results: Two doses of adjuvanted vaccine were required to induce HA inhibition (HI) antibody titers ≥ 40 in most participants. After two doses of the 15 µg H7N9 formulation, given with or without AS03 adjuvant, the proportion achieving a HI titer ≥ 40 against the vaccine strain at 21 days after the second vaccination was 65 % (95 % CI, 57 %-73 %) and 0 % (95 % CI, 0 %-4%), respectively. Among those who received two doses of the 15 µg adjuvanted formulation the proportion with HI titer ≥ 40 at 21 days after the second vaccination was 76 % (95 % CI, 66 %-84 %) in those 19-64 years of age and 49 % (95 % CI, 37 %-62 %) in those ≥ 65 years of age. Responses to the adjuvanted vaccine formulations did not vary by HA content. Antibody responses declined over time and responses against drifted H7N9 strains were diminished. Overall, the vaccines were well tolerated but, as expected, adjuvanted vaccines were associated with more frequent solicited systemic and local adverse events., Conclusions: AS03 adjuvant improved the immune responses to an inactivated fifth-wave H7N9 influenza vaccine, particularly in younger adults, but invoked lower responses to drifted H7N9 strains. These findings may inform future influenza pandemic preparedness strategies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [LAJ reports funding support to her institution from Pfizer for the conduct of a clinical trial of an investigational influenza vaccine. NGR is a paid safety consultant for ICON and EMMES, serves on the advisory boards for GSK, Moderna, Sanofi, and Seqirus and her institution received funds for the conduct of research from Sanofi, Lilly, Merck, Quidel, and Pfizer. MJM reported potential competing interests: laboratory research and clinical trials contract funding with Lilly, Pfizer, and Sanofi; personal fees for Scientific Advisory Board service from Merck, Meissa Vaccines, Inc. and Pfizer. EBW has received funding support from Pfizer, Moderna, Sequiris, Najit Technologies Inc, and Clinetic for the conduct of clinical trials and clinical research and has served as an advisor to Vaxcyte and consultant to ILiAD biotechnologies. CAR.’s institution has received funds to conduct clinical research unrelated to this manuscript from BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. She is co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.]., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this article, a multi-estimator based computationally efficient algorithm is developed for autonomous search in an unknown environment with an unknown source. Different from the existing approaches that require massive computational power to support nonlinear Bayesian estimation and complex decision-making process, an efficient cooperative active-learning-based dual control for exploration and exploitation (COAL-DCEE) is developed for source estimation and path planning. Multiple cooperative estimators are deployed for environment learning process, which is helpful to improving the search performance and robustness against noisy measurements. The number of estimators used in COAL-DCEE is much smaller than that of the particles required for Bayesian estimation in information-theoretic approaches. Consequently, the computational load is significantly reduced. As an important feature of this study, the convergence and performance of COAL-DCEE are established in relation to the characteristics of sensor noises and turbulence disturbances. Numerical and experimental studies have been carried out to verify the effectiveness of the proposed framework. Compared with the existing approaches, COAL-DCEE not only provides convergence guarantee but also yields comparable search performance using much less computational power.

Timely liver function recovery (LFR) is crucial for postoperative hepatocellular carcinoma (HCC) patients. Here, we established the significance of LFR on patient long-term survival through retrospective and prospective cohorts and identified a key gut microbe, Bifidobacterium longum, depleted in patients with delayed recovery. Fecal microbiota transfer from HCC patients with delayed recovery to mice similarly impacted recovery time post hepatectomy. However, oral gavage of B. longum improved liver function and repair in these mice. In a clinical trial of HCC patients, orally administering a probiotic bacteria cocktail containing B. longum reduced the rates of delayed recovery, shortened hospital stays, and improved overall 1-year survival. These benefits, attributed to diminished liver inflammation, reduced liver fibrosis, and hepatocyte proliferation, were associated with changes in key metabolic pathways, including 5-hydroxytryptamine, secondary bile acids, and short-chain fatty acids. Our findings propose that gut microbiota modulation can enhance LFR, thereby improving postoperative outcomes for HCC patients., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Reactions of N,N '- bis (3-methylpyridyl)oxalamide ( L 1 ), N , N '- bis (3-methylpyridyl)adipoamide ( L 2 ) and N , N '- bis (3-methylpyridyl)sebacoamide ( L 3 ) with tricarboxylic acids and Cu(II) salts afforded {[Cu( L 1 )(1,3,5-HBTC)]·H 2 O} n (1,3,5-H 3 BTC = 1,3,5-benzenetricarboxylic acid), 1 , {[Cu 1.5 ( L 2 ) 1.5 (1,3,5-BTC)(H 2 O) 2 ]·6.5H 2 O} n , 2 , [Cu( L 2 ) 0.5 (1,3,5-HBTB)] n (1,3,5-H 3 BTB = 1,3,5-tri(4-carboxyphenyl)benzene), 3 , [Cu 4 ( L 3 )(OH) 2 (1,3,5-BTC) 2 ] n , 4 , {[Cu 3 ( L 3 ) 2 (1,3,5-BTB) 2 ]·2.5MeOH·2H 2 O} n , 5 , and {[Cu 3 ( L 3 ) 2 (1,3,5-BTB) 2 ]·DMF·2H 2 O} n , 6 , which have been structurally characterized by using single crystal X-ray crystallography. Complexes 1-4 form a 2D layer with the {4 4 .6 2 }- sql topology, a 2D layer with the (4.6 2 ) 2 (4 2 .6 2 .8 2 )- bex topology, a three-fold interpenetrated 3D net with the (4 12 ·6 3 )- pcu topology and a 3D framework with the (4 10 ·6 32 ·8 3 )(4 2 ·6) 2 (4 3 ·6 3 ) topology, respectively, whereas 5 and 6 are 3D frameworks with the (6 3 ) 2 (6 4 ·8 2 )(6 8 ·8 5 ·10 2 ) topology. Complex 5 shows a better iodine adsorption factor of 290.0 mg g -1 at 60 °C for 360 min than the other ones, revealing that the flexibility of the spacer ligand governs the structural diversity and the adsorption capacity.

Background: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer., Methods: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis., Results: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications., Conclusions: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants., (© 2024. The Author(s).)

Probiotics hold great potential for treating metabolic diseases such as obesity. Given the complex and multifactorial nature of these diseases, research on probiotic combination with multiple targets has become popular. Here, we choose four obesity-related targets to perform high-throughput screening, including pancreatic lipase activity, bile salt hydrolase activity, glucagon-like peptide-1 secretion and adipocyte differentiation. Then, we obtained 649 multi-strain combinations with the requirement that each must cover all these targets in principle. After in vitro co-culture and in vivo co-colonization experiments, only four (<0.7%) combinations were selected as symbiotic probiotic communities (SPCs). Next, genome-scale metabolic model analysis revealed that these SPCs showed lower metabolic resource overlap and higher metabolic interaction potential involving amino acid metabolism (Ammonium, L-Lysine, etc.) and energy metabolism (Phosphate, etc.). Further animal experiments demonstrated that all SPCs exhibited a good safety profile and excellent effects in improving obesity and associated glucose metabolism disruptions and depression-like behaviors in high-fat-diet-fed mice. This anti-obesity improvement was achieved through reduced cholesterol level, fat accumulation and inhibited adipocyte differentiation. Taken together, our study provides a new perspective for designing multi-strain combinations, which may facilitate greater therapeutic effect on obesity and other complex diseases in the future.

Migraine, one of the most prevalent and debilitating neurological disorders, can be classified based on attack frequency into episodic migraine (EM) and chronic migraine (CM). Medication overuse headache (MOH), a type of chronic headache, arises when painkillers are overused by individuals with untreated or inadequately treated headaches. This study compares regional cortical morphological alterations and brain structural network changes among these headache subgroups. Sixty participants, including 20 in each of the following patient groups (EM, CM, MOH), and healthy controls (HC) completed the study. Our results show that the EM group exhibited cortical thickness (CTs) thinning predominantly in the left limbic, whereas CM patients exhibited CTs thinning across both left and right hemispheres. The MOH group demonstrated the most widespread CTs thinning. Both CM and MOH exhibited comparable patterns of CTs thinning within lobes, leading to reduced intra-lobe connectivity. While there were no significant differences in total inter-lobe connectivity between migraine groups and HC, both CM and MOH groups exhibited significantly decreased inter-limbic connectivity compared to HC and EM groups. In addition, they showed increased inter-frontal and inter-parietal connectivity, suggesting possible compensatory mechanisms to offset the loss of inter-lobe connectivity between the limbic and other lobes. Both CM and MOH groups exhibited a significant loss of global efficiency and a decrease in betweenness centrality in their brain networks, with MOH showing the most pronounced decrease and CM showing the second largest decrease. Our results suggest that aberrant structural brain networks in CM and MOH are less efficient, less centralization, and abnormally segregated., Competing Interests: Conflict of interest The authors have no conflict of interests to disclose., (Copyright © 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Emerging pollutants such as natural and manufactured chemicals, insecticides, pesticides, surfactants, and other biological agents such as personal care products, cosmetics, pharmaceuticals, and many industrial discharges hamper the aquatic environment. Nanomaterials and microplastics, among the categories of pollutants, can directly interfere with the marine ecosystem and translate into deleterious effects for humans and animals. They are either uncontrolled or poorly governed. Due to their known or suspected effects on human and environmental health, some chemicals are currently causing concern. The aquatic ecology is at risk from these toxins, which have spread worldwide. This review assesses the prevalence of emerging and hazardous pollutants that have effects on aquatic ecosystems and contaminated water bodies and their toxicity to non-target organisms. Microalgae are found to be a suitable source to remediate the above-mentioned risks. Microalgae based mitigation techniques are currently emerging approaches for all such contaminants, including the other categories that are discussed above. These studies describe the mechanism of phycoremediation, provide outrage factors that may significantly affect the efficiency of contaminants removal, and discuss the future directions and challenges of microalgal mediated remediations., 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 Elsevier Inc. All rights reserved.)

A new bicyclic lactam derivatives penicilactam B ( 1 ) and a new monocyclic amide penicillamide D ( 2 ), along with four known compounds ( 3-6 ), were isolated from the fermentation broth of the derived fungus Penicillium rubens PQJ-2. Their structures and stereochemistry were elucidated by comprehensive spectroscopic analyses and quantum ECD calculations. All the compounds were evaluated for their antibacterial activities against Staphylococcus aureus subsp , Candida albicans, Escherichia coli and insecticidal activity against Helicoverpa armigera Hubner. Compounds 1-3 exhibited modest insecticidal activity against H. armigera Hubner.

A new biphenyl compound: 5-aldehyde-4'-hydroxy-2,2'-dimethoxybiphenyl ( 1 ), along with 11 known phenolic compounds ( 2-12 ) were isolated from the stem of Ficus pumila Linn. Their structures were established by spectroscopic methods, including MS, UV, IR, 1 D and 2 D NMR. Compounds 4 and 10 showed weakly cytotoxicity against MCF-7, with IC 50 values of 32.5 and 37.3 µM, respectively.

Shigella-controlled human infection models (CHIMs) are an invaluable tool utilized by the vaccine community to combat one of the leading global causes of infectious diarrhea, which affects infants, children and adults regardless of socioeconomic status. The impact of shigellosis disproportionately affects children in low- and middle-income countries (LMICs) resulting in cognitive and physical stunting, perpetuating a cycle that must be halted. Shigella-CHIMs not only facilitate the early evaluation of enteric countermeasures and up-selection of the most promising products but also provide insight into mechanisms of infection and immunity that are not possible utilizing animal models or in vitro systems. The greater understanding of shigellosis obtained in CHIMs builds and empowers the development of new generation solutions to global health issues which are unattainable in the conventional laboratory and clinical settings. Therefore, refining, mining and expansion of safe and reproducible infection models hold the potential to create effective means to end diarrheal disease and associated co-morbidities associated with Shigella infection., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Indole-3-carbinol, bisindolylmethanes (BIMs) and indole-3-methanamines exhibit diverse therapeutic activities. Fluorinated molecules are widely used in pharmaceuticals. Herein we report a facile and straightforward method for the successful synthesis of difluoromethylated indole-3-carbinols, bisindolylmethanes and indole-3-methanamines by a Friedel-Crafts reaction. The reaction involves the in situ generation of difluoroacetaldehyde from difluoroacetaldehyde ethyl hemiacetal in the presence of a base or an acid. This protocol is distinguished by its good to excellent yields, broad substrate compatibility, good functional group tolerance and scalability.

Background: Few studies have focused on factors associated with futile recanalization in patients with an acute basilar artery occlusion (BAO) that was treated with modern endovascular therapy (EVT). The aim of this study was to explore the factors associated with futile recanalization in patients with an acute BAO presented within 12 h., Methods: This is a post-hoc analysis of the ATTENTION trial (The Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion, ClinicalTrials.gov, number NCT04751708). Demographics, clinical characteristics, acute stroke workflow interval times, and imaging characteristics were compared between the futile recanalization and favorable recanalization groups. The favorable outcome was defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, successful reperfusion was defined as thrombolysis in cerebral infarction (TICI) 2b and 3 on the final angiogram, and futile recanalization was defined as failure to achieve a favorable outcome despite successful reperfusion. A multivariate analysis was performed to identify the predictors of futile recanalization., Results: In total, 185 patients were included in the final analysis: 89 (48.1%) patients had futile recanalization and 96 (51.9%) patients had favorable recanalization. In the multivariable logistic regression analysis, older age (OR 1.04, 95% CI 1.01 to 1.08, p  = 0.01) and diabetes mellitus (OR 3.35, 95% CI 1.40 to 8.01, p  = 0.007) were independent predictors of futile recanalization., Conclusion: Futile recanalization occurred in nearly half of patients with acute BAO following endovascular treatment. Old age and diabetes mellitus were identified as independent predictors of futile recanalization after endovascular therapy for acute BAO., 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 © 2023 Yi, Li, Lin, Lin, Wu, Pan, Zheng, Chen, Zeng and Chen.)

While transition metals are useful for activating monopersulfate (MPS) to degrade contaminants, bimetallic alloys exhibit stronger catalytic activities owing to several favorable effects. Therefore, even though Co is an efficient metal for MPS activation, CoFe alloys are even more promising heterogeneous catalysts for MPS activation. Immobilization/embedment of CoFe alloy nanoparticles (NPs) onto hetero-atom-doped carbon matrices appears as a practical strategy for evenly dispersing CoFe NPs and enhancing catalytic activities via interfacial synergies between CoFe and carbon. Herein, N-doped carbon-embedded CoFe alloy (NCCF) is fabricated here to exhibit a unique hollow-engineered nanostructure and the composition of CoFe alloy by using Co-ZIF as a precursor after the facile etching and Fe doping. The Fe dopant embeds CoFe alloy NPs into the hollow-structured N-doped carbon substrate, enabling NCCF to possess the higher mesoscale porosity, active N species as well as more superior electrochemical properties than its analogue without Fe dopants, carbon matrix-supported cobalt (NCCo). Thus, NCCF exhibits a considerably larger activity than NCCo and the benchmark catalyst, Co 3 O 4 NP, for MPS activation to degrade an environmental hormone, dihydroxydiphenyl ketone (DHPK). Besides, NCCF + MPS shows an even lower activation energy for DHPK degradation than literatures, and retains its high efficiency for eliminating DHPK in different water media. DHPK degradation pathway and ecotoxicity assessment are unraveled based on the insights from the computational chemistry, demonstrating that DHPK degradation by NCCF + MPS did not result in the formation of toxic and highly toxic by-products. These features make NCCF a promising heterogeneous catalyst for MPS activation to degrade DHPK., 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 Elsevier Inc. All rights reserved.)

Many cancer cells exhibit enhanced glycolysis, which is seen as one of the hallmark metabolic alterations, known as Warburg effect. Substantial evidence shows that upregulated glycolytic enzymes are often linked to malignant growth. Using glycolytic inhibitors for anticancer treatment has become appealing in recent years for therapeutic intervention in cancers with highly glycolytic characteristic, including non-small cell lung cancer (NSCLC). In this work, we studied the anticancer effects and the underlying mechanisms of combination of benzerazide hydrocholoride (Benz), a hexokinase 2 (HK2) inhibitor and 64, a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor, in several NSCLC cell lines. We found that combination of Benz and 64 exhibited strong synergistic anticancer effects in NCI-H1975, HCC827, NCI-H1299 and SK-LU-1 cell lines. With this combination treatment, we observed changes of certain mechanistic determinants associated with metabolic stress caused by glycolysis restriction, such as mitochondrial membrane potential depolarization, overproduction of reactive oxygen species [1], activation of AMPK and down-regulation of mTOR, which contributed to enhanced apoptosis. Moreover, Benz and 64 together significantly suppressed the tumor growth in HCC827 cell mouse xenograft model. Taken together, our study may suggest that combined inhibition of HK2 and PDK1 using Benz and 64 could be a viable anticancer strategy for NSCLC., 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 Elsevier Inc. All rights reserved.)

Background: Prior studies suggested that antidepressant use is associated with an increased risk of dementia compared to no use, which is subject to confounding by indication. We aimed to compare the dementia risk among older adults with depression receiving first-line antidepressants (i.e., SSRI/SNRI) versus psychotherapy, which is also considered the first-line therapy for depression., Methods: This retrospective cohort study was conducted using the US Medical Expenditure Panel Survey from 2010 to 2019. We included adults aged ≥ 50 years diagnosed with depression who initiated SSRI/SNRI or psychotherapy. We excluded patients with a dementia diagnosis before the first record of SSRI/SNRI use or psychotherapy. The exposure was the patient's receipt of SSRI/SNRI (identified from self-report questionnaires) or psychotherapy (identified from the Outpatient Visits or Office-Based Medical Provider Visits files). The outcome was a new diagnosis of dementia within 2 years (i.e., survey panel period) identified using ICD-9/ICD-10 codes from the Medical Conditions file. Using a multivariable logistic regression model, we reported adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We also conducted subgroup analyses by patient sex, age group, race/ethnicity, severity of depression, combined use of other non-SSRI/SNRI antidepressants, and presence of underlying cognitive impairment., Results: Among 2,710 eligible patients (mean age = 61 ± 8, female = 69%, White = 84%), 89% used SSRIs/SNRIs, and 11% received psychotherapy. The SSRI/SNRI users had a higher crude incidence of dementia than the psychotherapy group (16.4% vs. 11.8%), with an aOR of 1.36 (95% CI = 1.06-1.74). Subgroup analyses yielded similar findings as the main analyses, except no significant association for patients who were aged < 65 years (1.23, 95% CI = 0.93-1.62), male (1.34, 95% CI = 0.95-1.90), Black (0.76, 95% CI = 0.48-1.19), had a higher PHQ-2 (1.39, 95% CI = 0.90-2.15), and had underlying cognitive impairment (1.06, 95% CI = 0.80-1.42)., Conclusions: Our findings suggested that older adults with depression receiving SSRIs/SNRIs were associated with an increased dementia risk compared to those receiving psychotherapy., (© 2023. The Author(s).)

Temperature is a key meteorological factor affecting ozone formation. In general, a positive correlation is observed between ozone and temperature, that is, ozone concentration increases with the increase in temperature. However, this relationship may change at extremely high temperatures. When the temperature exceeds a threshold value, the ozone concentration tends to decrease, which is referred to as an ozone suppression event. Ozone suppression events lead to greater uncertainties in the prediction of future air quality under climate change. Based on the national air quality monitoring data, reanalysis data, and meteorological observation data, this study used the Z test to systematically analyze the spatio-temporal characteristics of the critical temperature( T x ) and frequency of ozone suppression events in China during the warm season(April to September) from 2013 to 2020 and further analyzed the possible influencing factors for the occurrence of ozone suppression events. The results showed that approximately 18% of the sites in China experienced ozone suppression events in the warm season from 2013 to 2020. The sites with a high frequency of ozone suppression events were mainly distributed in the central and western regions of China, such as Sichuan, Xinjiang, and Shaanxi, with an average frequency of ten times per year. The critical temperature( T x ) ranged from 19.2 to 39.3℃, and the T x of most sites showed an increasing trend from 2013 to 2020. The high values of T x were mainly distributed in the central and western regions such as Sichuan, Chongqing, Hunan, and Hubei, whereas the low values of T x were concentrated in the Qinghai-Tibet Plateau. Contrary to the interannual trend of T x , the frequency of ozone suppression events decreased significantly in the Beijing-Tianjin-Hebei Region and exhibited a characteristic of "increase-decrease-increase" in the Fenwei Plain, the Yangtze River Delta, and the Chengdu-Chongqing regions. The most significant effect of extreme high temperature on ozone suppresion was found in the Pearl River Delta Region. In addition, ozone precursors(e.g., NO 2 ) and meteorological conditions(wind speed and direction) were possible factors affecting the occurrence of ozone suppression events.

In this study, we designed and synthesized a novel class of 1,3,4-oxadiazolyl-containing β-carboline derivatives, i.e., compounds f1∼f35 as potential α-glucosidase inhibitors. All the synthesized compounds possessed outstanding α-glucosidase inhibitory activity with the IC 50 values in the range of 3.07-15.49 μM, representing that they are 36∼183-fold more active than a positive control, acarbose (IC 50  = 564.28 μM). Among them, compound f26 exhibited the highest α-glucosidase inhibitory activity (IC 50  = 3.07 μM) and was demonstrated to function as a reversible and noncompetitive inhibitor. Mechanistic studies by means of 3D fluorescence spectra, CD spectra and molecular docking suggested that complexation of compound f26 with α-glucosidase through hydrogen bonds and hydrophobic interactions, led to changes in the conformation and secondary strictures of α-glucosidase and further the inhibition of the enzymatic activity. In vivo results showed that oral administration of compound f26 (50 mg/kg/day) could obviously reduce the levels of fasting blood glucose and improve glucose tolerance and dyslipidemia in diabetic mice. The present findings suggest that compound f26 is exploitable as a potential lead compound for the development of new α-glucosidase inhibitors with antidiabetic activity., 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 Elsevier Masson SAS. All rights reserved.)

Purpose: To investigate the expression and significance of NEK2 and EMT-related molecules in oral squamous cell carcinoma (OSCC)., Methods: The expression levels of NEK2 and EMT-related molecules (E-Cadherin, N-Cadherin, Vimentin) in 60 cases of primary OSCC tissues and normal oral mucosa tissues were detected by immunohistochemistry(IHC). NEK2 mRNA expression in 25 OSCC tissues and 10 normal oral mucosa tissues was detected by qRT-PCR. Statistical analysis was performed using SPSS 26.0 software package., Results: The expression of NEK2, N-Cadherin, and Vimentin increased in OSCC tissues, while the expression of E-Cadherin decreased(P＜0.05). The worse the differentiation, the higher the expression of NEK2 and the lower the expression of E-Cadherin(P＜0.05)., Conclusions: NEK2 can be used as a prognostic marker for OSCC. The up-regulation of NEK2 and the changes in the expression levels of EMT related molecules can promote the occurrence and development of OSCC.

Purpose: To investigate protein and genetic status of BRAF V600E in ameloblastomas, ameloblastic carcinomas and cysts, and to explore if recurrence and malignant transformation of ameloblastomas depends on BRAF status., Methods: Twenty cysts, 25 primary ameloblastomas, 25 recurrent ameloblastomas and 8 ameloblastic carcinomas were analysed by immunohistochemistry, and 2 cysts, 5 primary ameloblatomas, 5 recurrent ameloblastomas, 3 atypical ameloblastomas and 6 ameloblastic carcinomas were analysed by quantitative real-time PCR(qPCR). SPSS 26.0 software package was used for data analysis., Results: There was no correlation between BRAF V600E expression and recurrence. Cysts and carcinomas had lower frequencies of BRAF V600E mutations than ameloblastomas. There was a concordance between positive staining of BRAF V600E protein and BRAF V600E mutation., Conclusions: BRAF V600E mutation may be useful in the differential diagnosis of ameloblastomas with cysts and ameloblastic carcinomas. Immunohistochemistry may be a beneficial method to screen for BRAF V600E mutation in ameloblastoma.

Background: Intrauterine adhesion (IUA) results from serious complications of intrauterine surgery or infection and mostly remains incurable. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have emerged as a potential new approach for the treatment of IUA; however, their impact is not fully understood. Here, we performed a meta-analysis summarizing the effects of sEVs on IUA in preclinical rodent models., Methods: This meta-analysis included searches of PubMed, EMBASE, Cochrane, and the Web of Science databases from January 1, 1997, to April 1, 2022, to identify studies reporting the therapeutic effect of sEVs on rodent preclinical animal models of IUA. We compared improvements in endometrial thickness, endometrial gland number, fibrosis area, embryo number, vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGFβ1), and leukemia inhibitory factor (LIF) levels after treatment., Results: Our search included 100 citations, of which 7 met the inclusion criteria, representing 231 animals. Compared with that in the control group, the fibrosis area in the sEV-treated group was significantly reduced (standardized mean difference (SMD) = -6.87，95 % confidence interval (CI) = -9.67 to -4.07). The number of glands increased after the intervention (95 % CI, 3.72-7.68; P  = 0.000). Endometrial thickness was significantly improved in the sEV-treated group (SMD = 2.57, 95 % CI, 1.62-3.52)., Conclusions: This meta-analysis is highlighting that sEV treatment can improve the area of endometrial fibrosis, as well as VEGF, and LIF level, in a mouse IUA model. This knowledge of these findings will provide new insights into future preclinical research., 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. Published by Elsevier Ltd.)