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Xuan Zheng,1,* Bo Chen,1,* Jian-Xiong Wu,2 Angela Y Jia,3 Wei-Qi Rong,2 Li-Ming Wang,2 Fan Wu,2 Yu-Ting Zhao,1 Ye-Xiong Li,4 Wei-Hu Wang5 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Abdominal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA; 4Department of Radiation Oncology, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China *These authors contributed equally to this work Purpose: To evaluate the role of adjuvant radiotherapy after narrow-margin (

Lingdong Shao,* Qingqin Peng,* Kaixin Du,* Junyan He, Yaping Dong, Xiaoyi Lin, Jinluan Li, Junxin Wu Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The tumor cell (TC) PD-L1 expression has been reported by several studies in various types of cancer, and it reduces the cytotoxicity of T-cells toward cancer and evades the anticancer immune response. Herein, our study focuses on the impact of PD-L1 expression in prognosis and the correlation with clinical prognostic factors for local advanced rectal cancer with neoadjuvant radiotherapy (RT). A total of 68 rectal cancer patients treated with neoadjuvant RT were retrospectively enrolled in the present study. PD-L1 expression was investigated using immunohistochemistry. A regression model was used to identify prognostic factors associated with the disease-free survival, the local recurrence-free survival (LRFS), and the overall survival rates. The median follow-up was 32.5 months. Seven patients presented TC PD-L1 positive (TC PD-L1+), while the others were TC PD-L1 negative (TC PD-L1–). TC PD-L1+ patients showed frequent tumor recurrence than TC PD-L1– patients. Several patients with TC PD-L1– underwent long-course RT. TC PD-L1 expression was similar to interstitial cell (IC) PD-L1 expression, and the relationship between IC PD-L1 and pathological T stage was observed. TC PD-L1+ was related to poor LRFS. The multivariate analysis showed TC PD-L1+ as an independent negative prognostic factor for LRFS. In conclusion, TC PD-L1 expression putatively predicts the LRFS for patients with rectal cancer following neoadjuvant RT. The patients with TC PD-L1+ are susceptible to high local recurrent rate, thereby proposing a novel immunotherapeutic strategy for PD-L1 inhibition-mediated control. Keywords: PD-L1, rectal cancer, neoadjuvant radiotherapy, prognosis

Ailing Liu,1,2,* Jinxiang Wu,1,* Aijun Li,2 Wenxiang Bi,3 Tian Liu,1 Liuzhao Cao,1 Yahui Liu,1 Liang Dong1 1Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Pulmonary Diseases, Weihai Municipal Hospital, Weihai, Shandong, People’s Republic of China; 3Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Objectives: Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence) or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE) induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence.Methods: Human bronchial epithelial cells (16HBE cells) cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS), PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway.Results: Cellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence.Conclusion: CSE can induce cellular senescence in human bronchial epithelial cells, and ROS/PI3K/AKT/mTOR signaling pathway may play an important role in this process. C. sinensis can inhibit the CSE-induced senescence. Keywords: senescence, Cordyceps sinensis, ROS/PI3K/AKT/mTOR signaling pathway, COPD

Background and purposePatients with multigland primary hyperparathyroidism are at higher risk for missed lesions on imaging and failed parathyroidectomy. The purpose of this study was to prospectively validate the ability of previously derived predictive score systems, the composite multigland disease score, and the multiphase multidetector contrast-enhanced CT (4D-CT) composite multigland disease score, to identify patients with a high likelihood of multigland disease.Materials and methodsThis was a prospective study of 71 patients with primary hyperparathyroidism who underwent 4D-CT and successful parathyroidectomy. The size and number of lesions identified on 4D-CT, serum calcium levels, and parathyroid hormone levels were collected. A composite multigland disease score was calculated from 4D-CT imaging findings and the Wisconsin Index (the product of the serum calcium and parathyroid hormone levels). A 4D-CT multigland disease score was obtained by using the CT data alone.ResultsTwenty-eight patients with multigland disease were compared with 43 patients with single-gland disease. Patients with multigland disease had a significantly smaller lesion size (P < .01) and a higher likelihood of having either ≥2 or 0 lesions identified on 4D-CT (P < .01). Composite multigland disease scores of ≥4, ≥5, and 6 had specificities of 72%, 86%, and 100% for multigland disease, respectively. 4D-CT multigland disease scores of ≥3 and 4 had specificities of 74% and 88%.ConclusionsPredictive scoring systems based on 4D-CT data, with or without laboratory data, were able to identify a subgroup of patients with a high likelihood of multigland disease in a prospectively accrued population of patients with primary hyperparathyroidism. These scoring systems can aid in surgical planning.

Background: A significant research gap exists regarding the role of tissue exosomes in intrauterine adhesions (IUAs). This study aims to investigate the involvement of miR-195-5p and its regulatory network in IUAs through the analysis of tissue exosomes., Methods: Exosomes from rat uterine tissue with intrauterine adhesions were analyzed via transcriptomics to identify downstream target genes of miR-195-5p, cross-referencing with the human endometrial transcriptomics database GSE224093. Dual luciferase labeling confirmed miRNA-target gene interactions. The therapeutic efficacy of a miR-195-5p agonist was assessed in vivo through HE staining, Masson staining, and mating tests. The mechanisms underlying extracellular matrix (ECM) deposition and myofibroblast transdifferentiation in endometrial fibrosis were investigated both in vitro and in vivo using RT-PCR, Western Blot, immunofluorescence, and immunohistochemistry. Migration ability of endometrial stromal cells was evaluated using CCK8, scratch tests, and Transwell assays. Finally, the clinical potential of miR-195-5p was compared with autologous adipose-derived mesenchymal stem cells., Results: The expression of miR-195-5p in uterine tissue exosomes from intrauterine adhesions was found to be decreased. Treatment with a miR-195-5p agonist resulted in improved endometrial health, reduced fibrosis, increased glandular density, and enhanced birth rates in rats. Both in vivo and in vitro experiments confirmed that miR-195-5p decreased ECM deposition, reduced myofibroblast transdifferentiation, and inhibited the migration of endometrial stromal cells. This was achieved through the downregulation of YAP expression in the Hippo pathway and the upregulation of Smad7. Notably, the therapeutic efficacy of miR-195-5p agonists was comparable to that of stem cell therapy, offering promising avenues for clinical application., Conclusions: Differential expression of miR-195-5p in tissue exosomes can reduce ECM deposition and myofibroblast transdifferentiation, improving endometrial fibrosis by regulating the YAP-Smad7 pathway in the Hippo signaling cascade., Competing Interests: Declarations. Ethics approval and consent to participate: This study involves the collection of human endometrium and animal as part of the project titled ‘Study on the mechanism of miR-195-5p improving the epithelial-mesenchymal transformation of endometrial adhesion through YAP-SMAD7, which was approved by the Second Affiliated Hospital of Fujian Medical University Animal Care Committee (Approval No. and Date: 2023-179, May 18, 2023). Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

The automation of underground articulated vehicles is a critical step in advancing digital and smart mining. Current nonlinear model predictive control (NMPC) controllers face challenges such as delays in turning on large curvature paths and correction lags during the control of underground the Load-Haul-Dump (LHD). To address these issues, this paper proposes a PSO-NMPC control strategy that integrates a particle swarm optimization algorithm (PSO) into the NMPC controller to enhance path tracking for LHDs. To verify the effectiveness of the proposed PSO-NMPC control strategy, the local path of the tunnels is selected as the simulation path, comparing it with the pure NMPC controller based on the path characteristics of the actual tunnel. The results demonstrate that the improved NMPC controller significantly enhances the trajectory tracking performance of the LHD, with maximum absolute lateral deviations for experimental paths 2, 3, and 5 improved by 89.7%, 72.2%, and 68.9%, respectively. Additionally, the improved NMPC controller exhibits superior performance in paths with large curvature compared to those with very small curvature and straight-line paths, effectively addressing the challenges of turn delay and backward lag in LHD operation, thus providing practical significance., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Context: BRAF V600E mutation is the most common genetic driver of papillary thyroid cancer (PTC), where it is found with various allele frequency (AF), reflecting the proportion of cells carrying the mutant and wild-type gene alleles., Objective: To determine whether BRAF V600E AF can improve prognostication and inform initial surgical management of PTC., Design: Retrospective cohort study (2016-2019)., Setting: UCLA health., Patients: Consecutive patients with Bethesda V/VI nodules and isolated BRAF V600E mutation who underwent surgery with histopathology showing PTC., Interventions: Blinded ThyroSeq v3 molecular analysis after completion of initial management and follow-up., Main Outcomes Measures: Aggressive histopathology and cancer persistence/recurrence., Results: Of 73 patients, the median BRAF V600E AF was 25.5% (IQR, 16.7-34.3%). Higher median AF was seen in patients classified as American Thyroid Association (ATA) high-risk (37%) vs. intermediate-risk (25.3%, p<0.01) and low-risk (24.7%, p<0.01), largely attributed to higher AF in patients with gross extrathyroidal extension (ETE) (40.1% vs. 25.2% without gross ETE, p=0.02). No differences in AF were observed on the basis of lymph node positivity or presence of aggressive variants of PTC. A higher BRAF V600E AF was also found in patients with tumors ≥2cm vs. <2cm (median 32.0% vs. 24.4%, p<0.01). Over 4.1 years of follow-up, disease persistence/recurrence was found in 7 patients (9.4%) and was associated with higher median AF than those without recurrence (35.3% vs. 25.2%, p=0.02). Higher AF was associated with poorer recurrence-free survival (AF≥35%, HR 7.40, CI 1.4-38.1)., Conclusions: Higher AF was associated with gross ETE and increased recurrence risk. This may inform initial management in patients with PTC harboring an isolated BRAF V600E mutation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Higher center and surgeon volume correspond to better outcomes for patients with thyroid cancer. This study aims to investigate how a hospital's safety-net burden, the proportion of a hospital's patients who are insured by state Medicaid plans or are uninsured, influences the outcomes of high-volume (HV) surgeons. Methods: We performed a retrospective cohort study of all patients who underwent surgery for thyroid cancer in California from 1999 to 2017. We stratified treating facilities by the proportion of Medicaid-type and indigent payors into safety-net burden quartiles. We compared the perioperative and oncologic outcomes of HV surgeons (annual case volume ≥10) for patients undergoing total thyroidectomy across safety-net burden quartiles. A mixed-effects regression model controlled for surgeon random effects and fixed effects of patient and tumor characteristics. Results: Our sample comprised 42,347 patients (78% female, median age 50), of whom 13,848 (32%) were treated by HV surgeons ( n = 276). Compared to patients of lower-volume surgeons, patients of HV surgeons were more likely to be White, from the upper quartiles of socioeconomic status and well insured (all p < 0.001). HV surgeons in each hospital's safety-net burden quartile displayed similar case number distributions. Compared to patients treated by HV surgeons at Q1 (lowest safety-net burden) hospitals, those treated by HV surgeons at Q4 (highest safety-net burden) hospitals had higher absolute risks of endocrine complications (+7%, p = 0.007), airway complications (+6%, p = 0.004), disease-specific mortality (+1.3%, p = 0.046), and all-cause mortality during the study period (+3%, p = 0.046) in multivariable analysis. Conclusion: The performance of HV thyroid cancer surgeons differs by a hospital's safety-net burden, with patients treated at high safety-net burden hospitals experiencing higher rates of operative complications, disease-specific mortality, and all-cause mortality. Having a HV surgeon alone may be insufficient to provide optimal short- and long-term outcomes for patients with thyroid cancer.

Background: Giant salamander protein peptide is a peptide with rich functional properties. Giant salamander protein peptide KGEYNK (KK-6) is a peptide with both antioxidant and anti-inflammatory properties. The antioxidant and anti-inflammatory mechanisms of KK-6 are still unclear. When we studied the functional mechanism of KK-6, we found that the antioxidant property of KK-6 has a synergistic and promoting effect on anti-inflammatory properties., Results: KK-6 enhances cellular resistance to LPS via the MAPK/NF-κB signaling pathway, leading to increased levels of inflammatory factors: interleukin-1β (764.81 ng mL -1 ), interleukin-6 (1.06 ng mL -1 ) and tumor necrosis factor-α (4440.45 ng mL -1 ). KK-6 demonstrates potent antioxidant properties by activating the Nrf2 signaling pathway, resulting in elevated levels of antioxidant enzymes (glutathione peroxidase: 0.03 μg mL -1 ; superoxide dismutase: 0.589 μg mL -1 ) and a reduction in the concentration of the oxidative product malondialdehyde (967.05 μg mL -1 )., Conclusion: Our findings highlight the great potential of KK-6, a peptide extracted from giant salamander protein, as a remedy for intestinal inflammation. Through its dual role as an antioxidant and anti-inflammatory agent, KK-6 offers a promising avenue for alleviating inflammation-related damage and oxidative stress. This study lays the foundation for further exploration of giant salamander products and highlights their importance in health and novel food development. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Abstract: Platelet-rich plasma (PRP) shows promise as a regenerative modality for mild-to-moderate erectile dysfunction (ED). However, its efficacy in treating severe ED remains unknown. Blood samples from 8-week-old male rats were used to prepare PRP through a two-step centrifugation procedure, followed by chitosan activation and freeze thaw cycle. A hyperhomocysteinemia (HHcy)-related ED model was established using a methionine-enriched diet, and an apomorphine (APO) test was conducted during the 4 th week. APO-negative rats were divided into two groups and were injected with PRP or saline every 2 weeks. Erectile function and histological analyses of the corpus cavernosum were performed during the 16 th week. The results revealed that erectile function was significantly impaired in rats with HHcy-related ED compared to that in age-matched rats but was improved by repeated PRP injections. Immunofluorescence staining revealed a reduction in reactive oxygen species and additional benefits on the recovery of structures within the corpus cavernosum in rats that received PRP treatment compared to those in the saline-injected control group. Therefore, PRP could enhance functional and structural recovery in a severe HHcy-related ED model. A notable strength of the present study lies in the use of a repeated intracavernous injection method, mirroring protocols used in human studies, which offers more reliable results for translating the findings to humans., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown., Design: Retrospective cohort study., Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations., Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens., Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p  = 0.001), ASP/methotrexate-based (63.5%, p  = 0.011), or ASP/not otherwise specified-based (63.2%, p  < 0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW., Conclusion: These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option and provides a rationale and strategy for developing combination therapies., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Background: Thyroid storm is a rare but potentially lethal manifestation of thyrotoxicosis. Guidelines recommend nonoperative management of thyroid storm, but thyroidectomy can be performed if patients fail medical therapy or need immediate resolution of the storm. Outcomes of thyroidectomy for management of thyroid storm remain ill-defined., Methods: Using the National Inpatient Sample from 2016 to 2020, a retrospective analysis was conducted of patients admitted with thyroid storm. Outcomes of interest included operative complications and mortality. Multivariable logistic regression was performed to assess factors associated with receiving thyroidectomy and mortality., Results: An estimated 16,175 admissions had a diagnosis of thyroid storm. The incidence of thyroid storm increased from .91 per 100,000 people in 2016 to 1.03 per 100,000 people in 2020, with a concomitant increase in mortality from 2.9% to 5.3% ( P < .001). Operative intervention was pursued in 635 (3.9%) cases with a perioperative complication rate of 30%. On multivariable regression, development of acute decompensated heart failure (adjusted odds ratio [AOR] 1.66, 95% Confidence Interval [CI] 1.03-2.68, P = .037) and acute renal failure (AOR 2.10, 95% CI 1.17-3.75, P = .013) increased odds of receiving surgery. The same multivariable model did not show a significant association between thyroidectomy and mortality., Discussion: The incidence of thyroid storm and associated mortality increased during the study period. Thyroidectomy is rarely performed during the same admission, with an overall perioperative complication rate of 30% and no effect on mortality. Patients with acute decompensated heart failure and renal failure were more likely to receive an operative intervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC., Patients and Methods: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS)., Results: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature., Conclusions: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Insecticide resistance poses a significant challenge in the implementation of vector-borne disease control strategies. We have assessed the resistance levels of Aedes albopictus to deltamethrin and pyriproxyfen (PPF) in Fujian Province (China) and investigated the correlation between these resistance levels and mutations in the voltage-gated sodium channel (VGSC)., Methods: The WHO bioassay protocol was used to evaluate the resistance coefficient of Ae. albopictus to deltamethrin and PPF, comparing a susceptible population from the Foshan (FS) area with wild populations from the Sanming (SM), Quanzhou (QZ), Zhangzhou (ZZ), Putian (PT) and Fuzhou (FZ) areas in Fujian Province. Genomic DNA was analyzed by PCR and sequencing to detect knockdown resistance (kdr) in the VGSC, specifically at the pyrethroid resistance alleles V1016V, I1532I and F1534F. Molecular docking was also performed to analyze the binding interactions of PPF and its metabolite 4'-OH-PPF to cytochrome P450 (CYP) 2C19, 2C9 and 3A4 and Ae. albopictus methoprene-tolerant receptors (AeMet), respectively., Results: The analysis of resistance to deltamethrin and PPF among Ae. albopictus populations from the various regions revealed that except for the sensitive population in FS and the SM population, the remaining four regional populations demonstrated resistance levels ranging from 4.31- to 18.87-fold for deltamethrin and from 2.85- to 3.62-fold for PPF. Specifically, the FZ and PT populations exhibited high resistance to deltamethrin, whereas the ZZ and QZ populations approached moderate resistance levels. Also, the resistance of the FZ, PT and ZZ populations to PPF increased slowly but consistently with the increasing trend of deltamethrin resistance. Genomic analysis identified multiple non-synonymous mutations within the VGSC gene; the F1534S and F1534L mutations showed significant resistance to deltamethrin in Ae. albopictus. Molecular docking results revealed that PPF and its metabolite 4'-OH-PPF bind to the Ae. albopictus AeMet receptor and CYP2C19., Conclusions: The wild Ae. albopictus populations of Fujian Province showed varying degrees of resistance to deltamethrin and PPF and a trend of cross-resistance to deltamethrin and PPF. Increased vigilance is needed for potential higher levels of cross-resistance, especially in the PT and FZ regions., (© 2024. The Author(s).)

A strategy for constructing binary metal-organic cage (MOC)-based materials was developed. The cationic MOCs were covalently linked by organic linkers to a cationic extended network, whereas the anionic MOCs acted as counterions and were encapsulated in the network. Compared with the corresponding unary materials, the binary MOC-based materials exhibited improved porosity and adsorption performance.

Background: Areca nut (AN) is a traditional Chinese herbal medicine used for centuries to treat gastrointestinal (GI) disorders. Charred AN (CAN) is a processed product of AN with similar therapeutic effects. This study aimed to investigate the therapeutic mechanisms of AN and CAN for constipation via metabolomics and gut microbiota analysis., Methods: In this study, the rats were randomly divided into 5 groups ( n  = 6): control, constipation model, positive drug, AN treatment, and CAN treatment groups. Constipation was induced by intragastric administration of loperamide hydrochloride, followed by 14-day treatment with mosapride, AN, or CAN. The efficacy difference between AN and CAN was assessed by evaluating the weight gain, fecal water content, GI transit rate, colonic histopathology, serum levels of GI hormones, gut microbiota, and fecal metabolites., Results: The results demonstrated that both AN and CAN could alleviate loperamide-induced constipation. Furthermore, they significantly elevated the serum levels of motilin, vasoactive intestinal peptide, substance P, and acetylcholine. 16S rRNA analysis revealed that AN regulated the relative abundance of Bacillus , UCG-005 , norank&#95;f&#95;Muribaculaceae , Candidatus&#95;Saccharimonas , and Ruminococcus , whereas CAN modulate the relative abundance of Lactobacillus , Bacillus , norank&#95;f&#95;Muribaculaceae , Ruminococcus , unclassified&#95;f&#95;Oscillospiraceae , and unclassified&#95;f&#95;Prevotellaceae . Moreover, the metabolic profile of AN- and CAN-treated rats was also different, where AN treatment involved pathways of citrate cycle (TCA) and tyrosine, alanine, aspartate, and glutamate metabolisms. Whereas CAN treatment involved pathways of steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolisms. Spearman correlation analysis indicated a close relationship between gut microbiota and fecal metabolites., Conclusion: In summary, this study revealed that AN may protect GI mucosa, enhance GI motility, and alleviate constipation symptoms by regulating the relative abundance of specific gut microbiota ( Bacillus , UCG-005 , norank&#95;f&#95;Muribaculaceae , Candidatus&#95;Saccharimonas , Ruminococcus ) as well as citrate cycle or tyrosine, alanine, aspartate, and glutamate metabolic pathways. Furthermore, CAN was observed to promote gastric emptying and intestinal propulsion, thereby alleviating constipation, by modulating the relative abundance of specific gut microbiota ( Lactobacillus , Bacillus , norank&#95;f&#95;Muribaculaceae , Ruminococcus , unclassified&#95;f&#95;Oscillospiraceae , unclassified&#95;f&#95;Prevotellaceae ) as well as steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolic pathways., 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 © 2024 Wang, Wu, Zhang, Huang, Jiang and Li.)

Objectives: We introduced selpercatinib prior to radioactive iodine therapy prior to radioactive iodine therapy (RAI) for pediatric papillary thyroid cancer (PTC) to enhance the tumorical effects of RAI., Case Presentation: PTC has an excellent prognosis but is commonly associated with local and distant metastases. Successful complete response to the current standard of care, thyroidectomy with lymph node resection and RAI, is achieved in only a small minority of cases with metastases. The direct effect of tyrosine kinase inhibitors (TKIs) on tumor regression has been confirmed in several randomized controlled studies, while the increased RAI uptake has been reported in small case series, but typically TKIs are currently reserved third-line. Selpercatinib is a TKI that specifically has a durable effect in RET-fusion positive malignancies. We describe a 10-year-old Hispanic girl with metastatic PTC treated with total thyroidectomy and extensive lymph node resection. Evaluation for relevant genetic drivers of the malignancy revealed a strong overexpression of the RET tyrosine kinase domain indicative of a RET gene fusion. Selpercatinib 120 mg twice daily given orally was initiated prior to the initial dose of RAI to achieve further tumor regression by a direct cytostatic effect and then secondarily enhancement of RAI uptake. Minimal side effects occurred, specifically intermittent mild skin rashes that resolved. Resolution of distal lung metastases was noted on CT imaging. RAI was then administered 9 months afterward, with ultimately achievement of a low thyroglobulin level 1.0 ng/mL 11 months after RAI., Conclusions: In conclusion, selpercatinib given prior to the initial dose of adjunctive RAI for RET-fusion positive PTC is a well-tolerated intervention that further reduces tumor burden and potentially enhances the tumorcidal effects of RAI., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Norepinephrine transporter (NET; encoded by SLC6A2) reuptakes the majority of the released noradrenaline back to the presynaptic terminals, thereby affecting the synaptic noradrenaline level 1 . Genetic mutations and dysregulation of NET are associated with a spectrum of neurological conditions in humans, making NET an important therapeutic target 1 . However, the structure and mechanism of NET remain unclear. Here we provide cryogenic electron microscopy structures of the human NET (hNET) in three functional states-the apo state, and in states bound to the substrate meta-iodobenzylguanidine (MIBG) or the orthosteric inhibitor radafaxine. These structures were captured in an inward-facing conformation, with a tightly sealed extracellular gate and an open intracellular gate. The substrate MIBG binds at the centre of hNET. Radafaxine also occupies the substrate-binding site and might block the structural transition of hNET for inhibition. These structures provide insights into the mechanism of substrate recognition and orthosteric inhibition of hNET., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.

Background: Keratosis pilaris (KP) is a prevalent benign dermatological condition characterized by small bumps at the hair follicles alongside surrounding redness, significantly impacting both aesthetics and mental well-being., Objective: This study investigated the potential benefits of a non-cross-linked hyaluronic acid (HA) compound for treating KP., Methods: A split-body, investigator-blinded, randomized, intraindividual comparative clinical trial was conducted. The non-cross-linked HA compound was injected into KP-affected regions on both upper arms. The treatment was delivered across four sessions scheduled at 4-week intervals. Blinded physicians and patients assessed differences in erythema, skin roughness, and overall scores between treated and control areas at the final follow-up visit. At the 12th and 24th weeks post-treatment, a four-point scale was utilized to assess subjects' perceived treatment efficacy. Additionally, dermoscopic images, histological alterations, and adverse events were monitored., Results: Physician assessments revealed a significant reduction in roughness and overall scores for treated areas compared to controls. Patient self-assessments also reflected improvements in roughness, redness, and overall scores for treated sides at the final visit, with 35.71% of patients demonstrating sustained improvement in redness and 71.43% reporting persistent improvements in roughness at 24th weeks post-treatment. The dermatoscopic examinations revealed a notable enhancement in both the quantity of follicular plugs and the extent of erythema among the subjects in the treatment group. Histopathological outcomes also demonstrated improvement., Conclusion: This study suggests that the non-cross-linked HA compound effectively improves skin roughness and promotes hair shaft growth in KP treatment, demonstrating a favorable safety profile. These findings position it as a potentially viable alternative therapy in clinical practice., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The therapeutic efficacy of drugs is determined, to a certain extent, by the efficiency of drug delivery. The low efficiency of drug delivery systems (DDSs) is frequently associated with serious toxic side effects and can even prove fatal in certain cases. With the rapid development of technology, drug delivery has evolved from using traditional frameworks to using nano DDSs (NDDSs), endogenous biomaterials DDSs (EBDDSs), and living cell DDSs (LCDDSs). LCDDSs are receiving widespread attention from researchers at present owing to the unique advantages of living cells in targeted drug delivery, including their excellent biocompatibility properties, low immunogenicity, unique biological properties and functions, and role in the treatment of diseases. However, the theoretical basis and techniques involved in the application of LCDDSs have not been extensively summarized to date. Therefore, this review comprehensively summarizes the properties and applications of living cells, elaborates the various drug loading approaches and controlled drug release, and discusses the results of clinical trials. The review also discusses the current shortcomings and prospects for the future development of LCDDSs, which will serve as highly valuable insights for the development and clinical transformation of LCDDSs in the future., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The first wide-view image of multiple structural and phase transformations for MOFs, ranging from crystal state transformations to the extreme limit approaching liquid/glass phase, was presented. The process involves i) an initial crystalline transformation from square-layer framework [Co 2 (pybz) 2 (CH 3 COO) 2 ] ⋅ DMF (Co2) to a 3-fold interpenetrated and ordered vacancies contained framework [Co(pybz) 2 (CH 3 OH) 2 ] ⋅ 2CH 3 OH (CoM) due to in situ disassemble-reassemble, ii) thermal induced departure of a pair of cis-form coordinated methanol in CoM leads to amorphous framework a-dCoM, iii) glass transition to super-cooled liquid scl-dCoM, iv) obtaining MOF glass g-dCoM upon quenching the super-cooled liquid, and v) re-crystallization of super-cooled liquid generates 6-fold interpenetrated dia-net framework [Co(pybz) 2 ] 6n (rec-dCoM) under further heating. The access to glass from CoM, provides a new self-perturbation strategy to create MOF glasses without melting. The wider pore size distribution in amorphous/glassy MOFs than crystalline precursor achieved the first time selective hydrocarbon gas separation by breakthrough experiments, which bring efficient separation of 1 : 99 C 2 H 2 /C 2 H 4 by either a-dCoM or g-dCoM and produce polymer grade C 2 H 4 with purity≥99.5 % after a single adsorption process. Furthermore, the mixture of 50 : 50 C 3 H 6 /C 3 H 8 can be separated by a-dCoM., (© 2024 Wiley-VCH GmbH.)

Objectives: The centrifugal ultrafiltration-high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to determine the free perampanel (PER) concentration in children with epilepsy., Methods: Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations., Results: The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples ( r  = 0.793 > 0, P  < 0.001). Additionally, the free PER concentrations were significantly ( P  < 0.05) increased in valproic acid (VPA) co-therapy (9.87 ± 5.83) compared with non-VPA co-therapy (5.03 ± 4.57)., Conclusions: The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA., 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.)

Long-term grazing alters soil resource availability and microbial biomass stoichiometry in grassland ecosystems. Exploring the relationship between soil stoichiometric imbalance and microbial carbon use efficiency (CUE) in grazed desert steppe can help understand soil carbon dynamics from a microbial perspective. Based on a long-term grazing platform in Stipa breviflora desert steppe of Inner Mongolia established in 2004, taking heavy, moderate and light grazing intensities, using no grazing as a control, we measured soil available nutrients, microbial biomass and associated enzyme activities for their acquisition, and calculated soil microbial CUE using ecological stoichiometry. The results showed that grazing inhibited soil microbial CUE by 1.0%-10.3%. Soil C:N imbalance was significantly increased by 20.6% in the moderate grazing treatment, while both C:P imbalance and N:P imba-lance were significantly increased by 20.7% and 25.2% in the heavy grazing treatment, indicating that soil microbial communities were more susceptible to N and P limitation. Soil microbial communities maintained their stoichiometric balance by regulating the threshold of elemental stoichiometry ratios and the production of extracellular enzymes. Structural equation modelling (SEM) results indicated that stoichiometric imbalance indirectly affected microbial CUE by altering the threshold of elemental stoichiometry ratios, microbial biomass stoichiometry, and enzyme stoichiometry.

The current study presents the development process and initial validation of the Engagement in Athletic Training Scale (EATS), which was designed to evaluate athletes' engagement in athletic training. In study 1, item generation and initial content validity of the EATS were achieved. In study 2, the factor structure of the EATS was examined using exploratory factor analysis (EFA) and exploratory structural equation modeling (ESEM). Internal consistency reliabilities of the subscales were examined ( N  = 460). In study 3, factor structure, discriminant validity, internal consistency reliability, and nomological validity of the EATS were further examined in an independent sample ( N  = 513). Meanwhile, measurement invariance of the EATS across samples (study 2 and study 3) and genders was evaluated. Overall, results from the 3 rigorous studies provided initial psychometric evidence for the 19-item EATS and suggested that the EATS could be used as a valid and reliable measure to evaluate athletes' engagement in athletic training., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Wu, Zou, Wang, Zhang, Hu and Liu.)

Cervical cancer ranks as the fourth most prevalent form of cancer and is a significant contributor to female mortality on a global scale. Pitavastatin is an anti-hyperlipidemic medication and has been demonstrated to exert anticancer and anti-inflammatory effects. Thus, the purpose of this study was to evaluate the anticancer effect of pitavastatin on cervical cancer and the underlying molecular mechanisms involved. The results showed that pitavastatin significantly inhibited cell viability by targeting cell-cycle arrest and apoptosis in Ca Ski, HeLa and C-33 A cells. Pitavastatin caused sub-G1- and G0/G1-phase arrest in Ca Ski and HeLa cells and sub-G1- and G2/M-phase arrest in C-33 A cells. Moreover, pitavastatin induced apoptosis via the activation of poly-ADP-ribose polymerase (PARP), Bax and cleaved caspase 3; inactivated the expression of Bcl-2; and increased mitochondrial membrane depolarization. Furthermore, pitavastatin induced apoptosis and slowed the migration of all three cervical cell lines, mediated by the PI3K/AKT and MAPK (JNK, p38 and ERK1/2) pathways. Pitavastatin markedly inhibited tumor growth in vivo in a cancer cell-originated xenograft mouse model. Overall, our results identified pitavastatin as an anticancer agent for cervical cancer, which might be expanded to clinical use in the future.

This paper presents a new framework using MEMS flow sensors on turbine blades (SOTB) to investigate unsteady flow features of a rotating wind turbine. Self-heating flow sensors were implemented by the U18 complementary metal-oxide semiconductor (CMOS) MEMS foundry provided by Taiwan Semiconductor Research Institute (TSRI). Flow sensor chips with a size of 1.5 mm × 1.5 mm were parylene-coated, output via a wireless data acquisition system (WDAQ), and mounted at the root, middle and tip of a 1.2 m diameter semi-rigid turbine blade of a 400 W horizontal axis wind turbine (HAWT). The instantaneous angles of attack (AOAs) of the SOTB were found to be 46~62°, much higher than the general stall AOA of 15°, but were accurate considering the normal detection of the flow sensors. The computational fluid dynamics (CFD) simulation of the HAWT was also compared with the SOTB output. The onsite measurement herein revealed that the 3D secondary flow increment, mostly obvious near the middle part of the turbine blades, degraded both the sensor and the turbine performance and initially justified the onsite measurement application.

Background: The aim of this study was to classify distinct subgroups of adolescents based on the severity levels of their mobile phone addiction and to investigate how these groups differed in terms of their psychosocial characteristics. We surveyed a total of 2,230 adolescents using three different questionnaires to assess the severity of their mobile phone addiction, stress, anxiety, depression, psychological resilience, and personality. Latent class analysis was employed to identify the subgroups, and we utilized Receiver Operating Characteristic (ROC) curves and multinomial logistic regression for statistical analysis. All data analyses were conducted using SPSS 26.0 and Mplus 8.5., Methods: We classified the subjects into subgroups based on their mobile phone addiction severity, and the results revealed a clear pattern with a three-class model based on the likelihood level of mobile phone addiction ( p  < 0.05). We examined common trends in psychosocial traits such as age, grade at school, parental education level, anxiety levels, and resilience. ROC analysis of sensitivity versus 1-specificity for various mobile phone addiction index (MPAI) scores yielded an area under the curve (AUC) of 0.893 (95% CI, 0.879 to 0.905, p  < 0.001). We also determined diagnostic value indices for potential cutoff points ranging from 8 to 40. The optimal cutoff value for MPAI was found to be >14, which corresponded to the maximum Youden index (Youden index = 0.751)., Results: The latent classification process in this research confirmed the existence of three distinct mobile phone user groups. We also examined the psychosocial characteristics that varied in relation to the severity levels of addiction., Conclusion: This study provides valuable insights into the categorization of adolescents based on the severity of mobile phone addiction and sheds light on the psychosocial characteristics associated with different addiction levels. These findings are expected to enhance our understanding of mobile phone addiction traits and stimulate further research in this area., 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 © 2024 Wu, Jia, Li, Liu, Zhang, Zhang, Jia and Fan.)

Context: Use of artificial intelligence (AI) to predict clinical outcomes in thyroid nodule diagnostics has grown exponentially over the past decade. The greatest challenge is in understanding the best model to apply to one's own patient population, and how to operationalize such a model in practice., Evidence Acquisition: A literature search of PubMed and IEEE Xplore was conducted for English-language publications between January 1, 2015 and January 1, 2023, studying diagnostic tests on suspected thyroid nodules that used AI. We excluded articles without prospective or external validation, nonprimary literature, duplicates, focused on nonnodular thyroid conditions, not using AI, and those incidentally using AI in support of an experimental diagnostic outside standard clinical practice. Quality was graded by Oxford level of evidence., Evidence Synthesis: A total of 61 studies were identified; all performed external validation, 16 studies were prospective, and 33 compared a model to physician prediction of ground truth. Statistical validation was reported in 50 papers. A diagnostic pipeline was abstracted, yielding 5 high-level outcomes: (1) nodule localization, (2) ultrasound (US) risk score, (3) molecular status, (4) malignancy, and (5) long-term prognosis. Seven prospective studies validated a single commercial AI; strengths included automating nodule feature assessment from US and assisting the physician in predicting malignancy risk, while weaknesses included automated margin prediction and interobserver variability., Conclusion: Models predominantly used US images to predict malignancy. Of 4 Food and Drug Administration-approved products, only S-Detect was extensively validated. Implementing an AI model locally requires data sanitization and revalidation to ensure appropriate clinical performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

For the first time, hierarchical porous amorphous metal-organic frameworks (HP-aMOFs) containing ultramicropores, micropores, and mesopores were synthesized by etching a composite of MOF glass (agZIF-76) and ZnO using ammonia. These materials show potential applications in the adsorption of C2 hydrocarbons.

Until recently, chemical pesticides were one of the most effective means of controlling agricultural pests; therefore, the search for insecticide targets for agricultural pests has been an ongoing problem. Estrogen-related receptors (ERRs) are transcription factors that regulate cellular metabolism and energy homeostasis in animals. Silkworms are highly sensitive to chemical pesticides, making them ideal models for pesticide screening and evaluation. In this study, we detected ERR expression in key organs involved in pesticide metabolism in silkworms (Bombyx mori), including the fat body and midgut. Using ChIP-seq technology, many estrogen- related response elements were identified in the 2000-bp promoter region upstream of metabolism-related genes, almost all of which were potential ERR target genes. The ERR inhibitor, XCT-790, and the endocrine disruptor, bisphenol A, significantly inhibited expression of the ERR target genes, BmTreh-1, BmTret-1, BmPK, BmPFK, and BmHK, in the fat bodies of silkworms, resulting in pupation difficulties in silkworm larvae that ultimately lead to death. In addition, based on the clarification that the ERR can bind to XCT-790, as observed through biofilm interferometry, its three-dimensional spatial structure was predicted, and using molecular docking techniques, small-molecule compounds with a stronger affinity for the ERR were identified. In summary, utilizing the powerful metabolic regulatory function of ERR in Lepidoptera pests, the developed small molecule inhibitors of ERR can be used for future control of Lepidoptera pests., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dunaliella salina, a microalga that thrives under high-saline conditions, is notable for its high β-carotene content and the absence of a polysaccharide cell wall. These unique characteristics render it a prime candidate as a cellular platform for astaxanthin production. In this study, our initial tests in an E. coli revealed that β-ring-4-dehydrogenase (CBFD) and 4-hydroxy-β-ring-4-dehydrogenase (HBFD) genes from Adonis aestivalis outperformed β-carotene hydroxylase (BCH) and β-carotene ketolase (BKT) from Haematococcus pluvialis counterparts by two-fold in terms of astaxanthin biosynthesis efficiency. Subsequently, we utilized electroporation to integrate either the BKT gene or the CBFD and HBFD genes into the genome of D. salina. In comparison to wild-type D. salina, strains transformed with BKT or CBFD and HBFD exhibited inhibited growth, underwent color changes to shades of red and yellow, and saw a nearly 50% decline in cell density. HPLC analysis confirmed astaxanthin synthesis in engineered D. salina strains, with CBFD + HBFD-D. salina yielding 134.88 ± 9.12 μg/g of dry cell weight (DCW), significantly higher than BKT-D. salina (83.58 ± 2.40 μg/g). This represents the largest amount of astaxanthin extracted from transgenic D. salina, as reported to date. These findings have significant implications, opening up new avenues for the development of specialized D. salina-based microcell factories for efficient astaxanthin production., 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 Masson SAS. All rights reserved.)

Objective: Rurality is associated with higher incidence and higher disease-specific mortality for most cancers. Outcomes for rural and ultrarural ("frontier") patients with thyroid cancer are poorly understood. This study aimed to identify actionable deficits in thyroid cancer outcomes for rural patients. Methods: We queried linked California Cancer Registry and California Office of Statewide Health Planning and Development databases for patients diagnosed with thyroid cancer (1999-2017). We analyzed time from disease stage at diagnosis, time from diagnosis to surgery, receipt of appropriate radioactive iodine ablation, surveillance status, and overall and disease-specific mortality for urban, rural, and frontier patients. Cox and logistic regression models controlled for clinical and demographic covariates a stepwise manner. All incidence figures are expressed as a proportion of newly diagnosed cases. Results: Our cohort comprised 92,794 subjects: (65,475 women [70.6%]; mean age 50.0 years). Compared to urban patients, rural and frontier patients were more likely to be American Indian, White, uninsured, and from lower quintiles of socioeconomic status ( p  < 0.01). Distant disease at diagnosis was more common in rural (56.0 vs. 50.4 cases per 1000 new cases, p  < 0.01) and frontier patients (80.9 vs. 50.4 per 1000, p  < 0.01) compared to urban patients. The incidence of medullary thyroid cancer was greater in rural patients (17.9 vs. 13.6 cases per 1000, p  < 0.01) and frontier patients (31.0 vs. 13.6 per 1000, p  < 0.01) compared to urban patients. The incidence of anaplastic thyroid cancer was higher in frontier versus urban patients (15.5 vs. 7.1 per 1000, p  < 0.01). When compared to urban patients, rural and frontier patients were more often lost to follow-up (odds ratio [OR] 1.69 [confidence interval, CI 1.54-1.85], and OR 3.03 [CI 1.89-5.26], respectively) and had higher disease-specific mortality (OR 1.18 [CI 1.07-1.30], and OR 1.92 [CI 1.22-2.77], respectively). Rural and frontier residence was independently associated with being lost to follow-up, suggesting that it is a key driver of disparities. Conclusion: Compared to their urban counterparts, rural and frontier patients with thyroid cancer present with later-stage disease and experience higher disease-specific mortality. They also are more often lost to follow-up, which presents an opportunity for targeted outreach to reduce the observed disparities in outcomes.

Objective: To develop a simple screening questionnaire for persistent postural-perceptual dizziness (PPPD) and evaluate its screening ability. Methods: A convenience sample of 296 individuals who met the inclusion criteria between November 2021 and January 2023 were prospectively selected for three rounds of screening at the Vertigo Specialty Clinic of the Department of Otorhinolaryngology-Head and Neck Surgery in the First Hospital of Shanxi Medical University. In conjunction with expert opinion and statistical analysis, the first and second rounds of screening were used to modify and finalize the questionnaire entries, and the third round of screening was used to evaluate the questionnaire's screening ability. Independent sample t -test was used for inter group comparison, reliability and validity indicators were employed to screen and evaluate questionnaire entries, and the receiver operating characteristic (ROC) curve was plotted to determine the optimal cut-off value and corresponding sensitivity and specificity. Results: The final PPPD screening questionnaire entries included 21 items. In evaluating the reliability of this questionnaire, the Cronbach's alpha coefficient was 0.831, the half folding coefficient was 0.742, the content validity was 0.86, and the Kaiser-Meyer-Olkin (KMO) value in the structural validity was 0.811. Additionally, there were six factors with characteristic root>1 and a cumulative contribution rate of 62.62%. The area under the ROC curve of the screening questionnaire was 0.935 (95% CI : 0.877-0.992), and the optimal cut-off value was 8.5, with a sensitivity of 85.0%, a specificity of 85.5%, and a Kappa value of 0.653. Conclusion: The PPPD simple screening questionnaire designed in this study has a high sensitivity and specificity, making it a useful tool for identifying PPPD patients.

Telomere shortening is an important sign and driving factor of aging, but its association mechanisms and causal effects with other aging-related biochemical hallmarks are largely unknown. This study first performed comprehensive genetic analyses (eg, shared genetic analysis, pleiotropic analysis, and gene enrichment analysis) to detect the underlying molecular mechanisms for the associations between telomere length (TL) and aging-related biochemical hallmarks. Then, further bidirectional Mendelian randomization (MR) analyses investigated the causal effects between TL and other biochemical hallmarks. The genetic correlations were negative between TL and growth differentiation factor-15 (GDF15) (p = .024), C-reactive protein (p = .007), hemoglobin A1c (p = .007), and red blood cell (RBC) (p = .022), but positive between TL and insulin-like growth factor 1 (IGF-1) (p = .002) and white blood cell counts (p = .007). The increased TL has causal effects on the low levels of GDF15 (p = 3.73E-06), sex hormone binding globulin (p = 6.30E-06), testosterone (p = 5.56E-07), fasting insulin (p = 2.67E-05), and RBC (p = 1.54E-05), but the higher levels of IGF-1 (p = 3.24E-07). In conclusion, the observed phenotypic correlations between TL and aging-related biochemical hallmarks may arise from a combination of shared genetic components and causal effects. Telomere length is regarded as a driving hallmark for aging-related biochemical hallmarks., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We report the synthesis and structural characterization of a 2D metal-organic framework with AB-packing layers, [Co 2 (pybz) 2 (CH 3 COO) 2 ]·DMF ( Co2 , pybz= 4-(4-pyridyl)benzoate), containing a stable (4,4)-grid network fabricated by paddle-wheel nodes, ditopic pybz, and acetate ligands. After removal of the guest, the layer structure is retained but reorganized into an ABCD packing mode in the activated phase ( Co2a ). Consequently, the intralayer square windows (7.2 × 5.0 Å 2 ) close, while the interlayer separation is decreased slightly from 3.69 to 3.45 Å, leaving a narrow gap. Importantly, the dangling methyl group of the acetate with H-bonds to the adjacent layers and also the well-distributed π-π interactions between the aromatic rings of neighboring layers facilitate the structural stability. These weak supramolecular interactions further allow for favorable dynamic exfoliation of the layers, which promotes efficient adsorption of C 2 H 2 (41.6 cm 3 g -1 ) over CO 2 with an adsorption ratio of 6.3 (0.5 bar, 298 K). The effective separation performance of equimolar C 2 H 2 /CO 2 was verified by cycling breakthrough experiments and was even tolerable to moisture (R.H = 52%). DFT calculations, in situ PXRD, and PDF characterization reveal that the favorable retention of C 2 H 2 rather than that of CO 2 is due to its H-bond formation with the paddle-wheel oxygen atoms that triggers the increase in interlayer separation during C 2 H 2 adsorption.

Plant survival requires an ability to adapt to differing concentrations of nutrient and toxic soil ions, yet ion sensors and associated signaling pathways are mostly unknown. Aluminum (Al) ions are highly phytotoxic, and cause severe crop yield loss and forest decline on acidic soils which represent ∼30% of land areas worldwide. Here we found an Arabidopsis mutant hypersensitive to Al. The gene encoding a leucine-rich-repeat receptor-like kinase, was named Al Resistance1 (ALR1). Al ions binding to ALR1 cytoplasmic domain recruits BAK1 co-receptor kinase and promotes ALR1-dependent phosphorylation of the NADPH oxidase RbohD, thereby enhancing reactive oxygen species (ROS) generation. ROS in turn oxidatively modify the RAE1 F-box protein to inhibit RAE1-dependent proteolysis of the central regulator STOP1, thus activating organic acid anion secretion to detoxify Al. These findings establish ALR1 as an Al ion receptor that confers resistance through an integrated Al-triggered signaling pathway, providing novel insights into ion-sensing mechanisms in living organisms, and enabling future molecular breeding of acid-soil-tolerant crops and trees, with huge potential for enhancing both global food security and forest restoration., (© 2024. The Author(s).)