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Shao-Jun Zhao,1,2,* De-Hua Wang,1,2 Yan-Wei Li,1,2 Lei Han,1,2 Xing Xiao,1,2 Min Ma,3,* David Chi-Cheong Wan,4 An Hong,1,2 Yi Ma1,2 1Institute of Biomedicine, Department of Cellular Biology, Jinan University, 2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, 3College of traditional Chinese Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Jinan University, Guangdong, 4School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of China *These authors contributed equally to this work Abstract: A novel neuroendocrine peptide, pituitary adenylate cyclase activating peptide (PACAP), was found to have an important role in carbohydrate or lipid metabolism and was susceptible to dipeptidyl peptidase IV degradation. It can not only mediate glucose-dependent insulin secretion and lower blood glucose by activating VPAC2 receptor, but also raise blood glucose by promoting glucagon production by VPAC1 receptor activation. Therefore, its therapeutic application is restricted by the exceedingly short-acting half-life and the stimulatory function for glycogenolysis. Herein, we generated novel peptide-conjugated selenium nanoparticles (SeNPs; named as SCD), comprising a 32-amino acid PACAP-derived peptide DBAYL that selectively binds to VPAC2, and chitosan-modified SeNPs (SeNPs-CTS, SC) as slow-release carrier. The circulating half-life of SCD is 14.12 h in mice, which is 168.4- and 7.1-fold longer than wild PACAP (~5 min) and DBAYL (~1.98 h), respectively. SCD (10 nmol/L) significantly promotes INS-1 cell proliferation, glucose uptake, insulin secretion, insulin receptor expression and also obviously reduces intracellular reactive oxygen species levels in H2O2-injured INS-1 cells. Furthermore, the biological effects of SCD are stronger than Exendin-4 (a clinically approved drug through its insulinotropic effect), DBAYL, SeNPs or SC. A single injection of SCD (20 nmol/kg) into db/db mice with type 2 diabetes leads to enhanced insulin secretion and sustained hypoglycemic effect, and the effectiveness and duration of SCD in enhancing insulin secretion and reducing blood glucose levels are much stronger than Exendin-4, SeNPs or SC. In db/db mice, chronic administration of SCD by daily injection for 12 weeks markedly improved glucose and lipid profiles, insulin sensitivity and the structures of pancreatic and adipose tissue. The results indicate that SC can play a role as a carrier for the slow release of bioactive peptides and SCD could be a hopeful therapeutic against type 2 diabetes through the synergy effects of DBAYL and SeNPs. Keywords: pituitary adenylate cyclase activating peptide (PACAP)-derived peptide, nano-selenium, VPAC2 receptor, synergy effect, type 2 diabetes (T2D)

This report presents two probable cases of Lyme arthritis triggered by athletic activity or trauma. One patient had ankle swelling after he began a jogging program, and a second had knee swelling that followed a twisting injury. The report describes the three stages of the illness and presents diagnostic lab tests and the therapies used. Polymerase chain reaction (PCR) testing of the synovial fluid can be useful in diagnosing active Lyme arthritis, but it may yield a false-negative result when there has been recent remission of the arthritis. [ABSTRACT FROM AUTHOR]

Graves' disease has a multitude of presentations, and certain symptoms can mimic sports-related concerns such as overtraining. A review of three cases of Graves' disease in young athletes illustrates the spectrum of symptoms and the pathophysiology. Diagnosis involves a detailed patient history, physical exam, and appropriate lab studies, including a thyroid radioactive iodine uptake scan. Treatment consists of symptom management and antithyroid medication, radioactive iodine thyroid ablation, or, rarely, thyroidectomy. [ABSTRACT FROM AUTHOR]

It is crucial to develop highly efficient electrochemistry systems for sensitive detection of tumour markers. In this work, naphthalenediimide derivatives with electrochemical application potential were successfully synthesized and characterized. Electrochemistry and calculation of density functional theory (DFT) showed that 2,7-bis(4-(dimethylamino)phenyl)benzo[lmn] [3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NDI-1) was an ideal candidate for electrochemical probe construction. Subsequently, based on the cyclic catalytic effect between NDI-1 and K 2 S 2 O 8 , a satisfying composite of GO/NDI-1/AuNPs was prepared and used to construct electrochemical probe for the design of ingenious sandwiched electrochemical immunosensor. Taking alpha-fetoprotein (AFP) as the model target biomarker, the designed immunosensor showed good detection performance for AFP, which exhibited wide range of linear response (10 fg/mL - 10 ng/mL), low detection limit (3.3 fg/mL). Moreover, the proposed immunosensor has been successfully applied to AFP detection in human serum, which provides the possibility for clinical applications. The designed electrochemical system provides a new electrochemical probe for the construction of immunosensors and may be extended to the electroanalysis of other biomolecules with recognition units., 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 B.V. All rights reserved.)

Sleep deprivation (SD) can affect the adaptive thermogenesis in laboratory rodents, but the molecular mechanism and the crosstalk with other organs remain largely unknown. In order to investigate the effects and mechanisms of SD on thermoregulation and energy metabolism, here we measured the changes of body weight, body fat mass, body temperature, resting metabolic rate (RMR), and thermogenic gene expression in brown adipose tissue (BAT), white adipose tissue (WAT), skeleton muscle and liver in C57BL/6J mice during 7-day SD with rotating rod sleep deprivation device. Results showed that compared with the control group, the body weight and body fat mass of SD mice were decreased and RMR of SD mice increased. The gene expression of Ampk, Pgc1α and Ucp1 which related to thermogenesis in BAT and WAT were significantly increased, and the expression of Ampk, Serca1, Serca2 and Ucp3 which related to thermogenesis in skeletal muscle were significantly increased in SD mice. Taken together, these data demonstrated that 7-day SD enhanced the adaptive thermogenesis in mice by activating AMPK, including the upregulation of the AMPK - PGC1α - UCP1 pathway in BAT, and the AMPK - UCP3 and SLN - SERCA pathway in skeleton muscle. Our data provide the molecular evidence for SD-stimulated adaptive thermogenesis and energy metabolism in small mammals., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the impact of a nationally available continuing education online curriculum on Emergency Medical Services (EMS) clinician confidence and knowledge in caring for end-of-life (EOL) patients., Methods: This is a prospective observational study of EMS clinicians (emergency medical technicians [EMTs], advanced EMTs [AEMTs], and paramedics). EMS clinicians and physicians with both EMS and palliative care expertise developed two 20-min modules regarding: (1) communication skills (including death notification) and (2) hospice knowledge. EMS clinicians' subject confidence (modified Likert-scale) and knowledge were assessed electronically immediately before and after each module. Data analysis compared before and after module improvements in knowledge and confidence. Linear regressions analyzed baseline EOL skill confidence scores based on EMS agency, level of certification, and years of experience., Results: We analyzed completed datasets for 1825 EMS clinicians (979 EMTs, 112 AEMTs, and 734 paramedics) representing a heterogeneous cohort across different EMS agencies (617 private, 545 fire-based, 298 hospital-based, 61 third service, and 304 other) and all 50 states and the District of Columbia. After the communication module, the number of EMS clinicians who reported confidence in delivering bad news increased from 62% (1131/1825) to 80% (1468/1825) ( p  < 0.001). After the hospice module, the number of EMS clinicians who reported confidence in knowing what services hospice provides increased from 51% (925/1825) to 75% (1375/1825) ( p  < 0.001) and confidence in knowing what active dying patients look like from 57% (1033/1825) to 78% (1429/1835) ( p  < 0.001) in knowing what active dying patients look like. Linear regression demonstrated that before modules, EMS clinicians with more monthly EOL calls, those with more years of experience, and paramedics were more confident in their EOL skills than their peers. After module completion, those with the fewest years of experience (0-3 years) and EMTs gained significantly more confidence in communication skills than their peers., Conclusion: Asynchronous, online continuing education improves EMS clinician knowledge and confidence in caring for patients near the EOL. The greatest benefit in improved confidence was for EMTs and those with the fewest years of EMS experience., 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 article., (© 2024 The Author(s). Journal of the American College of Emergency Physicians Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Precise adjusting the band gaps in metal-organic frameworks (MOFs) is crucial for improving their visible-light absorption capacity during photocatalysis, presenting both a formidable challenge and a charming opportunity. This present study employed a symmetry-reduction strategy to pre-design six novel 4-connected ligands with systematic substituents (-NO2, -H, -tBu, -OCH3, -OH and -NH2) and synthesized the corresponding pillared-layer Zr-MOFs (NKM-668) retaining the hexaphenylbenzene fragment. Subsequently, the NKM-668 MOFs were transformed into large-π-conjugated hexabenzocoronene-based MOFs (pNKM-668) via the Scholl reaction. These twelve MOFs exhibited broad and tunable band gaps over 1.41 eV (ranging from 3.25 eV to 1.84 eV), and the photocatalytic CO2 conversion rate raised by 33.2-fold. This study not only enriches the type of hexaphenylbenzene-based MOFs, but also paves the way for nanographene-containing MOFs in the further application of photocatalysis., (© 2024 Wiley‐VCH GmbH.)

Background and Aim: China has used traditional Chinese medicine (TCM) to treat diseases for more than 2000 years. Traditionally, TCMs in medicine cabinets are arranged alphabetically or on the basis of experience, but this arrangement greatly affects dispensing efficiency. However, owing to the unique properties and qualities of TCM, very few automatic approaches or systems have specifically addressed TCM dispensing problems. Therefore, it is necessary to establish a method of optimizing the traditional Chinese medicine placement scheme (TCMPS) via computer algorithms to improve the work efficiency of pharmacists., Methods: A prescription dataset from a hospital in 2022 was obtained, and the association rule algorithm (ARA) was used to calculate the frequency of use for each type of TCM and the associations between different types of TCMs. On the basis of these association and frequency data, the optimal TCMPS was calculated using the simulated annealing algorithm (SAA) and then verified using the prescription dataset from 2023., Results: A total of 10,601 prescriptions were collected in 2022, involving 360 different TCMs, and each prescription contained an average of 9.485 TCMs, with Danggui (3628) being the most frequently used. When the threshold of support was set to 0.05 and the confidence was set to 0.8, 78 couplet medicines used in orthopedics clinics were found through ARA. When the threshold value of support was set to 0, the confidence was set to 0, and the rule length was 2, a total of 129,240 rules were obtained, indicating support between all pairwise TCMs. The TCMPS, calculated using SAA, had a correlation sum of 14.183 and a distance sum of 3.292. The TCMPS was verified using a prescription dataset from 2023 and theoretically improved the dispensing efficiency of pharmacists by approximately 50%., Conclusions: In this study, the ARA and SAA were successfully applied to pharmacies for the first time, and the optimal TCMPS was calculated. This approach not only significantly improves the dispensing efficiency of pharmacists and reduces patient waiting time but also enhances the quality of medical services and patient satisfaction, and provides a valuable reference for the development of smart medicine., (© 2024. The Author(s).)

Introduction: The World Health Organization declared an end to the global emergency status of COVID-19 in May of 2023. However, the impact of COVID-19 is far from over. Individuals who have recovered from COVID-19 continue to experience physiological, psychological, or cognitive symptoms, such as fatigue, shortness of breath, dizziness, and loss of smell or taste, known as long COVID. This review aims to describe the clinical characteristics of the upper respiratory tract infection (URTI) caused by SARS-CoV-2, and provide evidence for the prevention and treatment of SARS-CoV-2 infection by using nasal irrigation. COVID-19 and nasal irrigation: Nasal irrigation presents a promising adjunct to standard COVID-19 prevention and treatment protocols. This practice is theorized to diminish viral presence in the upper respiratory tract, a region identified as a primary site for SARS-CoV-2 replication and shedding. By facilitating the removal of viral particles and enhancing mucociliary clearance, nasal irrigation could potentially lessen the severity of URTI symptoms and slow transmission rates. The review consolidates current evidence of the efficacy and safety of this approach across various populations, underscoring its practicality in both preventive and therapeutic contexts., Conclusions: We recommend that saline nasal irrigation is an effective, safe and convenient strategy to prevent the transmission of SARS-CoV-2 and alleviate the symptoms of URTI across various age groups., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Song Li, Xi-Cai Sun, Zhong-Fei Wu, Li Hu, Jing-Jing Wang, Min Yin, Lei Cheng, De-Hui Wang.)

Hypericum perforatum , also known as "natural fluoxetine," is a commonly used herbal remedy for treating depression. It is unclear whether melatonin in plants regulated by the endogenous circadian clock system is like in vertebrates. In this work, we found that the melatonin signal and melatonin biosynthesis gene, serotonin N -acetyltransferase HpSNAT1 , oscillates in a 24-hour cycle in H. perforatum . First, we constructed a yeast complementary DNA library of H. perforatum and found a clock protein HpLHY that can directly bind to the HpSNAT1 promoter. Second, it was confirmed that HpLHY inhibits the expression of HpSNAT1 by targeting the Evening Element. Last, it indicated that HpLHY -overexpressing plants had reduced levels of melatonin in 12-hour light/12-hour dark cycle photoperiod, while loss-of-function mutants exhibited high levels, but this rhythm seems to disappear as well. The results revealed the regulatory role of LHY in melatonin biosynthesis, which may make an important contribution to the field of melatonin synthesis regulation.

The fundamental pathophysiological mechanism in the progression of chronic heart failure following acute myocardial infarction (AMI) is ventricular remodeling, in which innate and adaptive immunity both play critical roles. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to function in a range of pathological conditions, such as infections, inflammation, autoimmune diseases, and tumors. However, it is unclear how MDSCs contribute to cardiac remodeling following AMI. This study aimed to identify the function and underlying mechanism of MDSCs in controlling cardiac remodeling following AMI. Following AMI in mice, MDSCs frequencies changed dynamically, considerably increased on day 7 in blood, spleens, lymph nodes and hearts, and decreased afterwards. Consistently, mice with AMI displayed enhanced cardiac function on day 14 post-AMI, reduced infract size and higher survival rates on day 28 post-AMI following the adoptive transfer of MDSCs. Furthermore, MDSCs inhibited the inflammatory response by decreasing pro-inflammatory cytokine (TNF-α, IL-17, Cxcl-1, and Cxcl-2) expression, up-regulating anti-inflammatory cytokine (TGF-β1, IL-10, IL-4, and IL-13) expression, reducing CD3 + T cell infiltration in the infarcted heart and enhancing M2 macrophage polarization. Mechanistically, MDSCs improved the release of anti-inflammatory factors (TGF-β1 and IL-10) and decreased the injury of LPS-induced cardiomyocytes in vitro in a manner dependent on cell-cell contact. Importantly, blockade of IL-10 partially abolished the cardioprotective role of MDSCs. This study found that MDSCs contributed to the restoration of cardiac function and alleviation of adverse cardiac remodeling after AMI possibly by inhibiting inflammation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Time-restricted feeding (TRF) has the potential to modulate circadian rhythm and widely studied in humans and laboratory mice. However, less is known about the physiological responses to TRF in wild mammals. Here, we used Mongolian gerbils, Meriones unguiculatus, to explore the effect of 6-week TRF on gene expression related with circadian rhythm and inflammation. The TRF gerbils had higher cumulative food intake than the ad libitum (AL) group, but body mass, feeding frequency/time and metabolic rate did not differ between groups. In the hypothalamus, downregulation of rhythm-related genes Per3, Cry1 and Dbp was detected in the daytime-restricted feeding (DRF) group and Cry1 was downregulated in the nighttime-restricted feeding (NRF) group. In the liver, the expression of Per1/3, Rev-erbα/β and Dbp was lower, and Bmal1 was higher in the DRF than in AL group, while NRF gerbils showed no changes. In the colon, the expression of Bmal1 and Cry1 was higher but Per3, Rev-erbα/β and Dbp were lower in the DRF than in AL group. Further, the expression of inflammation-related genes such as NF-κB, IL-1β, IL-18 and Nlrp3 was lower in the liver of DRF gerbils, and IL-1β was lower both in the hypothalamus and liver of NRF gerbils. Moreover, the genes related with inflammation such as NF-κB, Nlrp3, IL-10/18/1β and Tnf-α were positively or negatively correlated with multiple rhythm-related genes in the central and peripheral organs. In conclusion, TRF, particularly DRF, could modulate rhythm-related genes in the central and peripheral tissues and reduce hepatic expression of inflammation-related genes in gerbils., Competing Interests: Declaration of competing interest The authors declared no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Organic photodetectors (OPDs) have received considerable attention owing to their superior absorption coefficient and tunable bandgap. The introduction of bulk-heterojunction (BHJ) structure aims to maximize charge generation, however, its response speed is constrained by the random distribution of donor and acceptor. Herein, a multiple-active layer design consisting of a single acceptor layer and a bulk-heterojunction layer (A/BHJ structure) is introduced, which combines the benefits of both the planar junction and the BHJ, improving photo-sensing. A transfer process is employed for this structure, which involves calculating the energy release rate at each interface, considering temperature and velocity. Consequently, the OPD with the A/BHJ structure is successfully fabricated through transfer printing, resulting in reduced dark current, superior detectivity (1.06 × 10 13 Jones), and rapid response, achieved by creating a high hole injection barrier and suppressing trap sites within the interfaces. By thoroughly investigating charge dynamics in the structure, the A/BHJ structure-based OPD attains large bandwidth detection with high signal-to-noise. An efficient wireless data communication system with digital-to-analog conversion is showcased using the A/BHJ structure-based OPD., (© 2024 Wiley‐VCH GmbH.)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD) are interventions used to relieve biliary obstruction. The utility of ERCP compared with PTBD is not fully understood from a utilization outcome standpoint. Our study compares readmission rates and hospitalization outcomes in ERCP and PTBD., Methods: Using the National Readmission Database (NRD) 2016 to 2020, we identified all patients with an ERCP or PTBD completed during admission. The study cohort was first analyzed by 3 weighted study arms including those admitted with cholangitis, biliary/pancreatic malignancy, and choledocholithiasis. Second, we analyzed the cohort by a 1:1, unweighted propensity match. The primary outcome was 30 day, 90 day, and 6 month readmission. Secondary outcomes were readmission/overall mortality, cost, and length of stay. Outcomes were analyzed using multivariate analysis., Results: A total of 621,735 admissions were identified associated with 589,796 ERCP and 31,939 PTBD. In the propensity matched cohort, PTBD had a higher readmission rate at 30 days (20.38% vs. 13.71% P<0.0001), 90 days (14.63% vs. 13.14%, P<0.0001) but lower rate at 6 months (8.50% vs. 9.67%, P=0.0003). Secondary outcomes included increased PTBD-associated hospital length of stay (9.01 d vs. 6.74 d, P<0.0001), hospitalization cost ($106,947.97 vs. $97,602.25, P<0.0001), and overall mortality (6.86% vs. 4.35%, P<0.0001). No major differences were found for mortality among readmissions at 30 days (7.19% vs. 6.88%, P=0.5382), 90 day (6.82% vs. 6.51%, P=0.5612), and 6 months (5.08% vs. 5.91%, P=0.1744)., Conclusions: ERCP demonstrated superior results compared with PTBD for readmission rates, length of stay and overall mortality. For failed ERCP cases, emerging data for Endoscopic ultrasound guided-biliary drainage (EUS-BD) offers potential over PTBD and may provide additional options for the future in tertiary referral centers with experience., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) are two new classes of antidiabetic agents. We aimed to evaluate the association between these two drug classes and risk of various vascular diseases, digestive diseases and fractures., Methods: Large randomized trials of SGLT2is and GLP-1RAs were included. Outcomes of interest were the various serious adverse events related to vascular diseases, digestive diseases and fractures. We performed meta-analyses using synthesize risk ratio (RR) and 95% confidence interval (CI) as effect size., Results: We included 27 large trials. SGLT2is had significant association with less hypertension (RR 0.70, 95% CI 0.54-0.91), hypertensive crisis (RR 0.63, 95% CI 0.47-0.84), varicose vein (RR 0.34, 95% CI 0.13-0.92), and vomiting (RR 0.55, 95% CI 0.31-0.97); but more spinal compression fracture (RR 1.73, 95% CI 1.02-2.92) and tibia fracture. GLP-1RAs had significant association with more deep vein thrombosis (RR 1.92, 95% CI 1.23-3.00), pancreatitis (RR 1.54, 95% CI 1.07-2.22), and cholecystitis acute (RR 1.51, 95% CI 1.08-2.09); but less rib fracture (RR 0.59, 95% CI 0.35-0.97). Sensitivity analyses suggested that our findings were robust., Conclusions: SGLT2is may have protective effects against specific vascular and digestive diseases, whereas they may increase the incidence of site-specific fractures (e.g., spinal compression fracture). GLP-1RAs may have protective effects against site-specific fractures (i.e., rib fracture), whereas they may increase the incidence of specific vascular and digestive diseases. These findings may help to make a choice between SGLT2is and GLP-1RAs in clinical practice., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Eggshell translucency is a widespread issue in the field of egg quality. Previous research has established that the heritability of eggshell translucency is relatively low or moderate. Scientists have also successfully identified SNP loci related to eggshell translucency on different chromosomes by using gene chips and single-variant GWAS. However, the specific impact of single or multiple genes on the trait of eggshell translucency remains unknown. In an effort to investigate this, we examined 170 SNPs associated with eggshell translucency obtained by our research group. We selected 966 half-sibling laying hens from 2 generations in 3 pure lines: Dwarf Layer-White, Rhode Island Red-White Strain, and Rhode Island Red. Eggs were collected from each hen over a period of 5 consecutive days, and eggshell translucency was measured using a grading method in which the hens were divided into 2 groups: an opaque group and a translucent group. We collected blood samples from the laying hens and extracted DNA. Time of flight mass spectrometry (TOF-MS) was used for genotyping to identify SNP loci that influence the trait of eggshell translucency. The results of our analysis revealed that using TOF-MS in 3 chicken strains, we were able to eliminate loci with low gene polymorphism, genetic effect contribution less than 1%, and deviation from Hardy-Weinberg equilibrium. Ultimately, 5 SNPs (Affx-50362599, rs15050262, rs312943734, rs316121113, and rs317389181) were identified on chromosomes 1, 5, and 19. Additionally, nine candidate genes (DCN, BTG1, ZFP92, POU2F1, NUCB2, FTL, GGNBP2, ACACA, and TADA2A) were found to be associated with these SNPs. No linkage disequilibrium relationship was observed between the 2 pairs of SNP loci on chromosomes 1 and 19. Based on previous studies on the formation mechanism of eggshell translucency, we hypothesize that NUCB2, FTL, and ACACA genes may be affecting the eggshell structure through different mechanisms, such as increase the water permeability or make thin of eggshell membrane, which promote moisture or part of other egg contents and ultimately lead to the formation of eggshell translucency. These findings validate and identify five SNP loci that regulate the translucency trait, and provide molecular markers for breeding non-translucent populations. Furthermore, this study serves as a reference for further investigation of the genetic regulatory mechanisms underlying eggshell translucency., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Ambient temperatures have great impacts on thermoregulation of small mammals. Brown adipose tissue (BAT), an obligative thermogenic tissue for small mammals, is localized not only in the interscapular depot (iBAT), but also in supraclavicular, infra/subscapular, cervical, paravertebral, and periaortic depots. The iBAT is known for its cold-induced thermogenesis, however, less has been paid attention to the function of BAT at other sites. Here, we investigated the function of BAT at different sites of the body during cold acclimation in a small rodent species. As expected, Brandt's voles (Lasiopodomys brandtii) consumed more food and reduced the body mass gain when they were exposed to cold. The voles increased resting metabolic rate and maintained a relatively lower body temperature in the cold (36.5 ± 0.27 °C) compared to those in the warm condition (37.1 ± 0.36 °C). During cold acclimation, the uncoupling protein 1 (UCP1) increased in aBAT (axillary), cBAT (anterior cervical), iBAT (interscapular), nBAT (supraclavicular), and sBAT (suprascapular). The levels of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, were higher in cBAT and iBAT in the cold than in the warm group. The pAMPK/AMPK and pCREB/CREB were increased in cBAT and iBAT during cold acclimation, respectively. These data indicate that these different sites of BAT play the cold-induced thermogenic function for small mammals., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Non-traditional seafood, such as spoon worms (Urechis unicinctus) and peanut worms (Sipunculus nudus), serves as both delicacies and potential solutions to the global food insecurity crisis. Despite being consumed primarily in parts of China, Korea, and Japan, the nutritional values especially the complex fatty acid compositions of these marine worms are difficult to characterize. To overcome this obstacle, we employed covalent adduct chemical ionization (CACI) tandem mass spectrometry for the de novo identification of their unusual polyunsaturated fatty acids (PUFA). Through this method, we identified several PUFA with polymethylene-interrupted (PMI) double bond configurations, including 22:3(7Z,13Z,16Z), a novel PUFA derived from sciadonic acid. U. unicinctus exhibits an exceptionally low n-6/n-3 PUFA ratio of 0.15, making it a potential functional food to counterbalance the n-6/n-3 imbalance in modern diets. S. nudus boasts notably high concentrations (∼3 %, wt/wt) of branched chain fatty acids (BCFA), exceeding typical levels found in dairy products., 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 Ltd. All rights reserved.)

Background: Warm compresses are the routine treatment for Meibomian gland dysfunction (MGD) in daily life, but in order to achieve satisfactory efficacy, the treatment needs to be sustained over a long time, which can have an impact on the patient compliance. A more convenient warm compresses will help improve the patient compliance. Therefore, the purpose of the study is to investigate the efficacy and safety of the disposable eyelid warming masks for treatment of dry eye disease (DED) due to MGD., Methods: This was a randomized, controlled, non-masked, two-center clinical trial. One hundred and forty-four patients were treated by the masks or the hot towel twice daily for 12 weeks. Patients were evaluated at baseline, 4-week and 12-week visits for subjective symptoms, objective signs and safety assessments, including ocular symptom scores, ocular surface disease index (OSDI), tear break-up time (BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT), meibum quality, meibum expressibility, and adverse events (AEs)., Results: A totle of 134 patients were followed in the study. The mean age of the masks group (14 males and 52 females) and the hot towel group (20 males and 48 females) was 43.7 ± 13.5 years and 39.5 ± 13.9 years, respectively. At 4-week visit, there were significant statistical differences in ocular symptom scores, OSDI and CFS between two groups (P < 0.05). Except for SIT, the treatment group showed a greater improvement in subjective symptoms and objective signs than the control group at 12-week visit. (P < 0.05). In addition, 40 AEs occurred in 27 patients (37.5%) in the treatment group, and 34 AEs occurred in 21 patients (29.17%) in the control group. No serious AEs were reported., Conclusions: The masks had a good efficacy and safety in the treatment of DED due to MGD, and might offer an attractive treatment option for some patients., Trial Registration: The study was registered at Chinese Clinical Trial Registry (ChiCTR1900025443) on August 26, 2019., (© 2024. The Author(s).)

Objective: To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined. Methods: Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted. Results: The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P =0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation ( P =0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P =0.216). Conclusions: The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

In this study, a conductive patch for a flexible organic optoelectronic device is proposed and implemented using a poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) polymer electrode based on a transfer process to achieve its high conductivity with an efficient conductive pathway. This PEDOT-dominant surface is induced by phase inversion during the transfer process owing to the solvent affinity of the PSS phase. The PEDOT:PSS patch formed by the transfer process minimizes the power loss in a flexible optoelectronic device due to the improved charge collection and suppressed leakage current responses. In addition, the bending stability of the flexible photoelectronic device is also enhanced by maintaining performance for 1000 bending cycles. Therefore, in the fabrication of a transparent flexible conductive PEDOT:PSS patch, the transfer process of a conducting polymer constitutes an effective strategy that can improve conductivity and embellished morphology.

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8 + regulatory T (Treg) hi /CXCL13 + exhausted T (Tex) lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC., Competing Interests: Declaration of interests W.-Z.Z.. received speech honoraria from AstraZeneca, Roche, Eli Lilly, and Pfizer outside the submitted work. Z.-M.Z. is a founder of Analytical BioSciences. Y.-L.W. received research funding from Roche and speech honoraria from AstraZeneca, Roche, Eli Lilly, Pfizer, and Sanofi, and he was a research consultant for AstraZeneca. Q.Z. reports honoraria from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche, and Sanofi outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) play critical roles in human development and health. Their intake is often effectively estimated solely based on seafood consumption, though the high intake of terrestrial animal-based foods with minor amounts of LCPUFA may be significant. Covalent adduct chemical ionization (CACI) tandem mass spectrometry is one approach for de novo structural and quantitative analysis of minor unsaturated fatty acids (FA), for which standards are unavailable. Here, CACI-MS and MS/MS are used to identify and quantify minor omega-3 LCPUFA of terrestrial animal foods based on the application of measured response factors (RFs) to various FA. American mean intakes of pork, beef, chicken, and eggs contribute 20, 27, 45, and 71 mg/day of docosahexaenoic acid (DHA), respectively. The estimated intake of omega-3 DHA, eicosapentaenoic acid, and docosapentaenoic acid from nonseafood sources is significant, at 164, 103, and 330 mg/day, greater than most existing estimates of omega-3 LCPUFA intake.