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Objective: To explore the feasibility of transthoracic cardiac shear wave elastography (SWE) for non-invasive quantitative measurement of myocardial stiffness in healthy volunteers (HV) and hypertrophic cardiomyopathy (HCM) patients, and analyze the relationship between myocardial shear wave velocity (SWV) and left ventricular diastolic function. Methods: A total of 16 HV who underwent health check-ups and 5 HCM patients who visited the Cardiology Outpatient Clinic at Fujian Medical University Affiliated Union Hospital from September 2022 to October 2023 were prospectively recruited. The SWE technique was used to measure SWV of the basal segment of the interventricular septum, including left ventricular long-axis myocardial shear wave velocity (LA-SWV) and short-axis myocardial shear wave velocity (SA-SWV). The intraclass correlation coefficient (ICC) was employed to evaluate the intra-observer and inter-observer consistency of SWV measurements. Spearman's correlation analysis was performed to evaluate the correlation between baseline characteristics, echocardiography parameters and SWV. Quantitative data were expressed as median (interquartile range) [ M ( Q 1 , Q 3 )]. Results: The HV group had the age of 34.5 (24.0, 51.0) years, including 8 males (50%); the HCM group had the age of 34.0 (27.0, 46.0) years, including 3 males (60%). The intra-observer and inter-observer ICC (95% CI ) for LA-SWV measurements were 0.806 (0.592-0.907) and 0.785 (0.471-0.949), respectively, indicating high consistency; the intra-observer and inter-observer ICC (95% CI ) for SA-SWV measurements were 0.746 (0.359-0.862) and 0.602 (0.245-0.834), indicating moderate consistency. LA-SWV [1.74 (1.65, 1.77) vs 1.25 (1.22, 1.33) m/s, P <0.001] and SA-SWV [1.98 (1.96, 2.15) vs 1.52(1.46, 1.55) m/s, P <0.001] were significantly higher in HCM group than those in HV group. There was no significant correlation between SWV and gender, age or body mass index (all P >0.05). In the left ventricular long-axis view, interventricular septal end-diastolic thickness (IVSDT) ( r =0.749, P <0.001), early diastolic mitral valve flow velocity/early diastolic mitral annular peak motion velocity (E/e') (r=0.669, P <0.001), and left ventricular mass index (LVMI) ( r =0.679, P <0.001) were positively correlated with LA-SWV, while e' ( r =-0.545, P <0.001) and late diastolic mitral annular peak motion velocity ( r =-0.489, P =0.021) were negatively correlated with LA-SWV. In the left ventricular short-axis view, IVSDT ( r =0.784, P <0.001), E/e' ( r =0.657, P <0.001), and LVMI ( r =0.660, P <0.001) were positively correlated with SA-SWV, while e' was negatively correlated with SA-SWV ( r =-0.658, P <0.001). Conclusions: The use of SWE technique to measure myocardial SWV can be applied to assess the stiffness differences between normal myocardium and HCM myocardium. Additionally, SWV is correlated with left ventricular diastolic function indices and can effectively evaluate the diastolic dysfunction of the left ventricle caused by HCM.

Aims: Type 2 diabetes (T2D) is a global health burden, more prevalent among individuals with attention deficit hyperactivity disorder (ADHD) compared to the general population. To extend the knowledge base on how ADHD links to T2D, this study aimed to estimate causal effects of ADHD on T2D and to explore mediating pathways., Methods: We applied a two-step, two-sample Mendelian randomization (MR) design, using single nucleotide polymorphisms to genetically predict ADHD and a range of potential mediators. First, a wide range of univariable MR methods was used to investigate associations between genetically predicted ADHD and T2D, and between ADHD and the purported mediators: body mass index (BMI), childhood obesity, childhood BMI, sedentary behaviour (daily hours of TV watching), blood pressure (systolic blood pressure, diastolic blood pressure), C-reactive protein and educational attainment (EA). A mixture-of-experts method was then applied to select the MR method most likely to return a reliable estimate. We used estimates derived from multivariable MR to estimate indirect effects of ADHD on T2D through mediators., Results: Genetically predicted ADHD liability associated with 10% higher odds of T2D (OR: 1.10; 95% CI: 1.02, 1.18). From nine purported mediators studied, three showed significant individual mediation effects: EA (39.44% mediation; 95% CI: 29.00%, 49.73%), BMI (44.23% mediation; 95% CI: 34.34%, 52.03%) and TV watching (44.10% mediation; 95% CI: 30.76%, 57.80%). The combination of BMI and EA explained the largest mediating effect (53.31%, 95% CI: -1.99%, 110.38%) of the ADHD-T2D association., Conclusions: These findings suggest a potentially causal, positive relationship between ADHD liability and T2D, with mediation through higher BMI, more TV watching and lower EA. Intervention on these factors may thus have beneficial effects on T2D risk in individuals with ADHD.

Malignancies can compromise systemic innate immunity, but the underlying mechanisms are largely unknown. Here, we find that tumor-derived small extracellular vesicles (sEVs; TEVs) deliver PD-L1 to host macrophages, thereby impeding antibacterial immunity. Mice implanted with Rab27a-knockdown tumors are more resistant to bacterial infection than wild-type controls. Injection of TEVs into mice impairs macrophage-mediated bacterial clearance, increases systemic bacterial dissemination, and enhances sepsis score in a PD-L1-dependent manner. Mechanistically, TEV-packaged PD-L1 inhibits Bruton's tyrosine kinase/PLCγ2 signaling-mediated cytoskeleton reorganization and reactive oxygen species generation, impacting bacterial phagocytosis and killing by macrophages. Neutralizing PD-L1 markedly normalizes macrophage-mediated bacterial clearance in tumor-bearing mice. Importantly, circulating sEV PD-L1 levels in patients with tumors can predict bacterial infection susceptibility, while patients with tumors treated with αPD-1 exhibit fewer postoperative infections. These findings identify a mechanism by which cancer cells dampen host innate immunity-mediated bacterial clearance and suggest targeting TEV-packaged PD-L1 to reduce bacterial infection susceptibility in tumor-bearing conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, β4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Programmed death-ligand 1 (PD-L1) on tumor-derived small extracellular vesicles (sEVs) limits therapeutic effectiveness by interacting with the PD-1 receptor on host immune cells. Targeting the secretion of sEV PD-L1 has emerged as a promising strategy to enhance immunotherapy. However, the lack of small-molecule inhibitors poses a challenge for clinical translation. In this study, we developed a target and phenotype dual-driven high-throughput screening strategy that combined virtual screening with nanoflow-based experimental verification. We identified ibuprofen (IBP) as a novel inhibitor that effectively targeted sEV PD-L1 secretion. IBP disrupted the biogenesis and secretion of PD-L1 + sEVs in tumor cells by physically interacting with a critical regulator of sEV biogenesis, hepatocyte growth factor-regulated tyrosine kinase substrate. Notably, the mechanism of action of IBP is distinct from its commonly known targets, cyclooxygenases. Administration of IBP stimulated antitumor immunity and enhanced the efficacy of anti-PD-1 therapy in melanoma and oral squamous cell carcinoma mouse models. To address potential adverse effects, we further developed an IBP gel for topical application, which demonstrated remarkable therapeutic efficacy when combined with anti-PD-1 treatment. The discovery of this specific small inhibitor provides a promising avenue for establishing durable, systemic antitumor immunity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Cholinergic neurons in the basal forebrain play a crucial role in regulating adult hippocampal neurogenesis (AHN). However, the circuit and molecular mechanisms underlying cholinergic modulation of AHN, especially the initial stages of this process related to the generation of newborn progeny from quiescent radial neural stem cells (rNSCs), remain unclear. Here, we report that stimulation of the cholinergic circuits projected from the diagonal band of Broca (DB) to the dentate gyrus (DG) neurogenic niche promotes proliferation and morphological development of rNSCs, resulting in increased neural stem/progenitor pool and rNSCs with longer radial processes and larger busy heads. Interestingly, DG granule cells (GCs) are required for DB-DG cholinergic circuit-dependent modulation of proliferation and morphogenesis of rNSCs. Furthermore, single-nucleus RNA sequencing of DG reveals cell type-specific transcriptional changes in response to cholinergic circuit stimulation, with GCs (among all the DG niche cells) exhibiting the most extensive transcriptional changes. Our findings shed light on how the DB-DG cholinergic circuits orchestrate the key niche components to support neurogenic function and morphogenesis of rNSCs at the circuit and molecular levels., Competing Interests: Competing interests statement:The authors declare no competing interest.

Despite the widespread prevalence and important medical impact of insomnia, effective agents with few side effects are lacking in clinics. This is most likely due to relatively poor understanding of the etiology and pathophysiology of insomnia, and the lack of appropriate animal models for screening new compounds. As the main homeostatic, circadian, and neurochemical modulations of sleep remain essentially similar between humans and rodents, rodent models are often used to elucidate the mechanisms of insomnia and to develop novel therapeutic targets. In this article, we focus on several rodent models of insomnia induced by stress, diseases, drugs, disruption of the circadian clock, and other means such as genetic manipulation of specific neuronal activity, respectively, which could be used to screen for novel hypnotics. Moreover, important advantages and constraints of some animal models are discussed. Finally, this review highlights that the rodent models of insomnia may play a crucial role in novel drug development to optimize the management of insomnia., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: To provide a preoperative prediction model for lymph node metastasis in pancreatic cancer patients and provide molecular information of key radiomic features., Methods: Two cohorts comprising 151 and 54 pancreatic cancer patients were included in the analysis. Radiomic features from the tumor region of interests were extracted by using PyRadiomics software. We used a framework that incorporated 10 machine learning algorithms and generated 77 combinations to construct radiomics-based models for lymph node metastasis prediction. Weighted gene coexpression network analysis (WGCNA) was subsequently performed to determine the relationships between gene expression levels and radiomic features. Molecular pathways enrichment analysis was performed to uncover the underlying molecular features., Results: Patients in the in-house cohort (mean age, 61.3 years ± 9.6 [SD]; 91 men [60%]) were separated into training (n = 105, 70%) and validation (n = 46, 30%) cohorts. A total of 1,239 features were extracted and subjected to machine learning algorithms. The 77 radiomic models showed moderate performance for predicting lymph node metastasis, and the combination of the StepGBM and Enet algorithms had the best performance in the training (AUC = 0.84, 95% CI = 0.77-0.91) and validation (AUC = 0.85, 95% CI = 0.73-0.98) cohorts. We determined that 15 features were core variables for lymph node metastasis. Proliferation-related processes may respond to the main molecular alterations underlying these features., Conclusions: Machine learning-based radiomics could predict the status of lymph node metastasis in pancreatic cancer, which is associated with proliferation-related alterations., (© 2024. The Author(s).)

Naoxintong Capsule (NXT), a renowned traditional Chinese medicine (TCM) formulation, has been broadly applied in China for more than 30 years. Over decades, accumulating evidences have proven satisfactory efficacy and safety of NXT in treating cardiovascular and cerebrovascular diseases (CCVD). Studies have been conducted unceasingly, while this growing latest knowledge of NXT has not yet been interpreted properly and summarized comprehensively. Hence, we systematically review the advancements in NXT research, from its chemical constituents, quality control, pharmacokinetics, to its profound pharmacological activities as well as its clinical applications in CCVD. Moreover, we further propose specific challenges for its future perspectives: 1) to precisely clarify bioactivities of single compound in complicated mixtures; 2) to evaluate the pharmacokinetic behaviors of NXT feature components in clinical studies, especially drug-drug interactions in CCVD patients; 3) to explore and validate its multi-target mechanisms by integrating multi-omics technologies; 4) to re-evaluate the safety and efficacy of NXT by carrying out large-scale, multicenter randomized controlled trials. In brief, this review aims to straighten out a paradigm for TCM modernization, which help to contribute NXT as a piece of Chinese Wisdom into the advanced intervention strategy for CCVD therapy., 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 Zhang, Chen, Tang, Li, Wang, Wu, Xu, Zou, Luo, Ouyang, Chen, Liao and Wu.)

Women are more vulnerable to stress and have a higher likelihood of developing mood disorders. The serotonin (5HT) system has been highly implicated in stress response and mood regulation. However, sex-dependent mechanisms underlying serotonergic regulation of stress vulnerability remain poorly understood. Here, we report that adult hippocampal neural stem cells (NSCs) of the Ascl1 lineage (Ascl1-NSCs) in female mice express functional 5HT1A receptors (5HT1ARs), and selective deletion of 5HT1ARs in Ascl1-NSCs decreases the Ascl1-NSC pool only in females. Mechanistically, 5HT1AR deletion in Ascl1-NSCs of females leads to 5HT-induced depolarization mediated by upregulation of 5HT7Rs. Furthermore, repeated restraint stress (RRS) impairs Ascl1-NSC maintenance through a 5HT1AR-mediated mechanism. By contrast, Ascl1-NSCs in males express 5HT7R receptors (5HT7Rs) that are downregulated by RRS, thus maintaining the Ascl1-NSC pool. These findings suggest that sex-specific expression of distinct 5HTRs and their differential interactions with stress may underlie sex differences in stress vulnerability., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In the past 40 years, the incidence of esophagogastric junction cancer has been gradually increasing worldwide. Currently, surgical resection remains the main radical treatment for early gastric cancer. Due to the rise of functional preservation surgery, proximal gastrectomy has become an alternative to total gastrectomy for surgeons in Japan and South Korea. However, the methods of digestive tract reconstruction after proximal gastrectomy have not been fully unified. At present, the principal methods include esophagogastrostomy, double flap technique, jejunal interposition, and double tract reconstruction. Related studies have shown that double tract reconstruction has a good anti-reflux effect and improves postoperative nutritional prognosis, and it is expected to become a standard digestive tract reconstruction method after proximal gastrectomy. However, the optimal anastomoses mode in current double tract reconstruction is still controversial. This article aims to review the current status of double tract reconstruction and address the aforementioned issues., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To establish a nasopharyngeal carcinoma-specific big data platform based on electronic health records (EHRs) to provide data support for real-world study of nasopharyngeal carcinoma., Methods: A multidisciplinary expert team was established for this project. Based on industry standards and practical feasibility, the team designed the nasopharyngeal carcinoma data element standards including 14 modules and 640 fields. Data from patients diagnosed with nasopharyngeal carcinoma who visited Southern Hospital after 1999 were extracted from 15 EHRs systems and were cleaned, structured, and standardized using information technologies such as machine learning and natural language processing. In addition, a series of measures such as quality control and data encryption were taken to ensure data quality and patient privacy. At the platform application level, 10 functional modules were designed according to the needs of nasopharyngeal carcinoma research., Results: As of 1 October 2022, the Big Data platform has included 11,617patients, of whom 8228 (70.83 %) were male and 3389 (29.17 %) were female, with a median age of 48 years (interquartile range, 40 years). The data in the platform were validated to have a high level of completeness and accuracy, especially for key variables such as social demographics, laboratory tests and vital signs. Currently, six projects involving risk factors, early diagnosis, treatment efficacy and prevention of treatment-related toxic reactions have been conducted on the platform., Conclusions: We have established a high-quality NPC-specific big data platform by integrating heterogeneous data from multiple sources in the EHR. The platform provides an effective tool and strong data support for real-world studies of nasopharyngeal carcinoma, which helps to improve research efficiency, reduce costs, and improve the quality of research results. We expect to promote multicenter nasopharyngeal carcinoma data sharing in the future to facilitate the generation of high-quality real-world evidence in nasopharyngeal carcinoma. This article may provide some reference value for other comprehensive hospitals to establish a big data platform for nasopharyngeal carcinoma., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic pain often leads to the development of sleep disturbances. However, the precise neural circuit mechanisms responsible for sleep disorders in chronic pain have remained largely unknown. Here, we present compelling evidence that hyperactivity of pyramidal neurons (PNs) in the anterior cingulate cortex (ACC) drives insomnia in a mouse model of nerve-injury-induced chronic pain. After nerve injury, ACC PNs displayed spontaneous hyperactivity selectively in periods of insomnia. We then show that ACC PNs were both necessary for developing chronic-pain-induced insomnia and sufficient to mimic sleep loss in naive mice. Importantly, combining optogenetics and electrophysiological recordings, we found that the ACC projection to the dorsal medial striatum (DMS) underlies chronic-pain-induced insomnia through enhanced activity and plasticity of ACC-DMS dopamine D1R neuron synapses. Our findings shed light on the pivotal role of ACC PNs in developing chronic-pain-induced sleep disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Organic molecules are of great interest for gas sensing applications. However, achieving high-performance gas sensors with high sensitivity, fast response, low consumption, and workability in humid conditions is still challenging. Herein, we report the rational design and synthesis of an ion-in-conjugation polymer, PADC (poly-4,4'-azodianiline-croconamide), obtained by the condensation of croconic acid with 4-4'diaminoazobenzene for gas sensing under humid conditions. The as-fabricated PADC-based gas sensor exhibits ultrahigh sensitivity (802.7 ppm -1 at 1 ppm), subppb detection limit, and high selectivity under humid air with an 80% humidity effect at a temperature down to 350 K. PADC shows good planarity, excellent thermostability, and a narrow band gap of 1.2 eV because of azobenzene fragments spacing previously repulsed biphenyl rings. Compared to previous humidity immunity works, PADC-based sensors realized humidity immunity at a relatively lower temperature, resulting in lower energy consumption.

Reducing non-radiative recombination energy loss (ΔE nonrad ) in organic solar cells (OSCs) has been considered an effective method to improve device efficiency. In this study, the backbone of PTBTT-4F/4Cl is divided into D1-D2-D3 segments and reconstructed. The isomerized TPBTT-4F/4Cl obtains stronger intramolecular charge transfer (ICT), thus leading to elevated highest occupied molecular orbital (HOMO) energy level and reduced bandgap (E g ). According to E Loss  = E g- qV OC , the reduced E g and enhanced open circuit voltage (V OC ) result in lower E Loss , indicating that E Loss has been effectively suppressed in the TPBTT-4F/4Cl based devices. Furthermore, compared to PTBTT derivatives, the isomeric TPBTT derivatives exhibit more planar molecular structure and closer intermolecular stacking, thus affording higher crystallinity of the neat films. Therefore, the reduced energy disorder and corresponding lower Urbach energy (E u ) of the TPBTT-4F/4Cl blend films lead to low E Loss and high charge-carrier mobility of the devices. As a result, benefitting from synergetic control of molecular stacking and energetic offsets, a maximum power conversion efficiency (PCE) of 15.72% is realized from TPBTT-4F based devices, along with a reduced ΔE nonrad of 0.276 eV. This work demonstrates a rational method of suppressing V OC loss and improving the device performance through molecular design engineering by core segmentation and isomerization., (© 2023 Wiley-VCH GmbH.)

Incorporating ITIC derivatives as guest acceptors into binary host systems is an effective strategy for constructing high-performance ternary organic solar cells (TOSCs). In this work, we introduced A-D-A type ITIC derivatives PTBTT-4F (asymmetric) and PTBTP-4F (symmetric) into the PM6:BTP-BO-4F (Y6-BO) binary blend and investigated the impacts of two guest acceptors on the performance of TOSCs. Differentiated device performance was observed, although PTBTT-4F and PTBTP-4F presented similar chemical structures and comparable absorptions. The PTBTT-4F ternary devices exhibited an improved power conversion efficiency ( PCE ) of 17.67% with increased open circuit ( V OC ) and current density ( J SC ), whereas the PTBTP-4F-based ternary devices yielded a relatively lower PCE of 16.34%. PTBTT-4F showed much better compatibility with the host acceptor BTP-BO-4F, so that they formed a well-mixed alloy phase state; more precise phase separation and increased crystallinity were thus induced in the ternary blends, leading to reduced molecular recombination and improved charge mobilities, which contributed to improved fill factors of the ternary devices. In addition, the optimized PTBTT-4F devices exhibited good performance tolerance of the photoactive layer thickness, as they even delivered a PCE of 15.25% when the active layer was as thick as up to ∼300 nm.

Purpose: To evaluate the safety and effectiveness of endovascular treatment for massive haemoptysis caused by pulmonary pseudoaneurysm (PAP)., Methods: The clinical data, imaging data, and endovascular treatment protocol of 23 patients with massive haemoptysis caused by continuous PAP were retrospectively analysed. The success, complications, postoperative recurrence rate, and influence of the treatment on pulmonary artery pressure were also evaluated., Results: Nineteen patients with a bronchial artery-pulmonary artery (BA-PA) and/or nonbronchial systemic artery-pulmonary artery (NBSA-PA) fistula underwent bronchial artery embolization (BAE) and/or nonbronchial systemic artery embolization (NBSAE) + pulmonary artery embolization (PAE). The pulmonary artery (PA) pressures before and after embolization were 52.11 ± 2.12 (35-69 cmH 2 O) and 33.58 ± 1.63 (22-44 cmH 2 O), respectively (P = 0.001). Four patients did not have a BA-PA and/or NBSA-PA fistula. Embolization was performed in two patients with a distal PAP of the pulmonalis lobar arteria. Bare stent-assisted microcoils embolization was performed in the other two patients with a PAP of the main pulmonary lobar arteries. The PA pressures of the four patients before and after treatment were 24.50 ± 1.32 (22-28 cmH 2 O) and 24.75 ± 1.70 (22-29 cmH 2 O), respectively (P = 0.850). The technique had a 100% success rate with no serious complications and a postoperative recurrence rate of 30%., Conclusion: Endovascular treatment is safe and effective for massive haemoptysis caused by PAP. BAE and/or NBSAE can effectively reduce pulmonary hypertension in patients with a BA-PA and/or NBSA-PA fistula., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Insomnia is often comorbid with depression, but the underlying neuronal circuit mechanism remains elusive. Recently, we reported that GABAergic ventral pallidum (VP) neurons control wakefulness associated with motivation. However, whether and how other subtypes of VP neurons regulate arousal and emotion are largely unknown. Here, we report glutamatergic VP (VP Vglut2 ) neurons control wakefulness and depressive-like behaviors. Physiologically, the calcium activity of VP Vglut2 neurons was increased during both NREM sleep-to-wake transitions and depressive/anxiety-like behaviors in mice. Functionally, activation of VP Vglut2 neurons was sufficient to increase wakefulness and induce anxiety/depressive-like behaviors, whereas inhibition attenuated both. Dissection of the circuit revealed that separated projections of VP Vglut2 neurons to the lateral hypothalamus and lateral habenula promote arousal and depressive-like behaviors, respectively. Our results demonstrate a subtype of VP neurons is responsible for wakefulness and emotion through separated projections, and may provide new lines for the intervention of insomnia and depression in patients., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors.)

The unique structural advantages give metal-organic frameworks (MOFs) a special use as host substrates to encapsulate organic dyes, which would result in specific host-guest composites for white-light phosphors. In this work, an anionic MOF exhibiting blue emission was constructed using bisquinoxaline derivatives as photoactive centers, which could effectively encapsulate rhodamine B (Rh B) and acriflavine (AF) to form an In-MOF ⊃ Rh B/AF composite. By simply adjusting the amount of Rh B and AF, the emitting color of the resulting composite could be easily adjusted. The formed In-MOF ⊃ Rh B/AF composite exhibits broadband white light emission with ideal Commission International ed'Eclairage (CIE) coordinates of (0.34, 0.35), a color rendering index of 80.8, and a moderately correlated color temperature value of 5193.96 K. This strategy can be easily extended to other blue-emitting MOFs and dyes, thus opening up new prospects for the development of white-light-emitting materials.

Objective: Glucose 6-phosphate dehydrogenase (G6PD) deficiency increases the risk of neonatal hyperbilirubinemia. The aim of this study is to evaluate the risk factors associated with hyperbilirubinemia in infants from the western part of Guangdong Province, and to assess the contribution of G6PD deficiency to neonatal jaundice., Methods: The term infants with neonatal hyperbilirubinemia in People's Hospital of Yangjiang from June 2018 to July 2022 were recruited for the retrospective analysis. All the infants underwent quantitative detection of the G6PD enzyme. The etiology was determined through laboratory tests and clinical manifestations., Results: Out of 1,119 term infants, 435 cases presented with jaundice. For the etiology analysis, infection was responsible for 16.09% (70/435), G6PD deficiency accounted for 9.66% (42/435), of which 3 were complicated with acute bilirubin encephalopathy), bleeding accounted for 8.05% (35/435), hemolytic diseases accounted for 3.45% (15/435), and breast milk jaundice accounted for 2.53% (11/435). One case (0.23%) was attributed to congenital hypothyroidism, multiple etiologies accounted for 22.3% (97/435), and 35.63% (155/435) were of unknown etiology. Of the jaundiced infants, 19.54% (85/435) had G6PD deficiency, while only 10.23% (70/684) of non-jaundiced infants had G6PD deficiency; this difference was found to be statistically significant ( P  < 0.001). Furthermore, the hemoglobin levels in the jaundiced infants with G6PD deficiency (146.85 ± 24.88 g/L) were lower than those without G6PD deficiency (156.30 ± 22.07 g/L) ( P  = 0.001). 65 jaundiced infants with G6PD deficiency underwent G6PD mutation testing, and six different genotypes were identified, including c.95A > G, c.392G > T, c.1024C > T, c.1311C > T, c.1376G > T, c.1388G > A, c.871G > A/c.1311C > T, c.392G > T/c.1388G > A, and c.1376G > T/c.1311C > T.65iciency., Conclusion: In newborns in Yangjiang, G6PD deficiency, infection, and neonatal hemolytic disease were identified as the main causes of hyperbilirubinemia and acute bilirubin encephalopathy. Specifically, Hemolytic factors in infants with G6PD deficiency may lead to reduced hemoglobin and increased bilirubin levels in jaundiced infants., 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., (© 2023 Yang, Lin, Lin, Chen, Liao, Huang, Xiao, Huang, Xu, Chen, Cao and Yang.)

Introduction: Although the Tibetan medicine Triphala (THL) is widely used in many countries, insufficient progress has been made in quality control., Objectives: The present study aimed to propose a methodology for quality control of THL based on HPLC fingerprinting combined with an orthogonal array design., Methods: Seven identified peaks were used as indicators to examine the effects of temperature, extraction time, and solid-liquid ratio on the dissolution of active ingredients in THL. Fingerprint analysis was performed on 20 batches of THL from four geographical areas (China, Laos, Thailand, and Vietnam). For further chemometric assessment, analysis techniques including similarity analysis, hierarchical clustering analysis, principal component analysis, and orthogonal partial least squares discrimination analysis (OPLS-DA) were used to classify the 20 batches of samples., Results: Fingerprints were established and 19 common peaks were identified. The similarity of 20 batches of THL was more than 0.9 and the batches were divided into two clusters. Four differential components of THL were identified based on OPLS-DA, including chebulinic acid, chebulagic acid, and corilagin. The optimal extraction conditions were an extraction time of 30 min, a temperature of 90°C, and a solid-liquid ratio of 30 mL/g., Conclusion: HPLC fingerprinting combined with an orthogonal array design could be used for comprehensive evaluation and quality assessment of THL, providing a theoretical basis for further development and utilization of THL., (© 2023 The Authors. Phytochemical Analysis published by John Wiley & Sons Ltd.)

As a highly infectious pathogen, Bombyx mori nuclear polyhedrosis virus (BmNPV) has a high lethality rate in silkworm. Our previous study have confirmed that Hsp90 plays a positive role in BmNPV proliferation and Hsp90 inhibitor, geldanamycin (GA) can decrease the replication of BmNPV in vitro. However, its molecular mechanism is not fully understood. In the present study, first, we found that GA could inhibit the proliferation of BmNPV in a dose-dependent manner and delay the pathogenesis of BmNPV in vivo possibly by altering the transcript level of genes associated with cell apoptosis and immune pathways. Furthermore, by immunoprecipitation (IP) and mass spectrometry analysis, we identified a series of proteins potentially interacting with Hsp90 including two BmNPV encoded proteins. Subsequently, by Co-IP we confirmed the interaction between BmActin-4 and BmHsp90. Knocking down Bmhsp90 by small interfering RNA inhibited the protein expression level of BmActin-4. Over-expression of Bmactin-4 promoted the replication of BmNPV whereas knockdown of Bmactin-4 suppressed BmNPV replication. In addition, decrease of the transcript level of Bmhsp90 in Bmactin-4 knocking down BmN cells was also detected. Taken together, BmHsp90 can interact with BmActin-4 and promote its expression, thereby promoting BmNPV proliferation. Our findings may enrich the molecular mechanism of Hsp90 for promoting virus proliferation and provide new clues to elucidate the interact mechanism between silkworm and virus., Competing Interests: Declaration of competing interest The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Neonatal hyperbilirubinemia is one of the common diseases of newborns that typically presents with yellow staining of skin, resulting in sequelaes such as hearing loss, motor and intellectual development disorders, and even death. The pathogenic factors of neonatal hyperbilirubinemia are complex. Different cases of hyperbilirubinemia may have a single or mixed etiology., Aim: To explore the etiological characteristics of severe hyperbilirubinemia in term newborns of eastern Guangdong of China., Methods: Term newborns with severe hyperbilirubinemia in one hospital from January 2012 to December 2021 were retrospectively analyzed. The etiology was determined according to the laboratory results and clinical manifestations., Results: Among 1602 term newborns with hyperbilirubinemia in eastern Guangdong of China, 32.20% (580/1602) was severe hyperbilirubinemia. Among the causes of severe hyperbilirubinemia, neonatal hemolysis accounted for 15.17%, breast milk jaundice accounted for 12.09%, infection accounted for 10.17%, glucose-6-phosphate dehydrogenase (G6PD) deficiency accounted for 9.14%, and the coexistence of multiple etiologies accounted for 6.55%, unknown etiology accounted for 41.72%. ABO hemolysis and G6PD deficiency were the most common causes in the 20 cases with bilirubin encephalopathy. 94 severe hyperbilirubinemia newborns were tested for uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)*6 variant (rs4148323, c.211G>A, p.Arg71Gly), 9 cases were 211 G to A homozygous variant, 37 cases were 211 G to A heterozygous variant, and 48 cases were wild genotypes., Conclusion: The main cause for severe hyperbilirubinemia and bilirubin encephalopathy in eastern Guangdong of China were the hemolytic disease of the newborns, G6PD deficiency and infection. UGT1A1 gene variant was also a high-risk factor for neonatal hyperbilirubinemia. Targeted prevention and treatment according to the etiology may reduce the occurrence of bilirubin encephalopathy and kernicterus., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is characterized by a progressive loss of memory that cannot be efficiently managed by currently available AD therapeutics. So far, most treatments for AD that have the potential to improve memory target neural circuits to protect their integrity. However, the vulnerable neural circuits and their dynamic remodeling during AD progression remain largely undefined., Methods: Circuit-based approaches, including anterograde and retrograde tracing, slice electrophysiology, and fiber photometry, were used to investigate the dynamic structural and functional remodeling of a GABAergic circuit projected from the medial septum (MS) to the dentate gyrus (DG) in 3xTg-AD mice during AD progression., Results: We identified a long-distance GABAergic circuit that couples highly connected MS and DG GABAergic neurons during spatial memory encoding. Furthermore, we found hyperactivity of DG interneurons during early AD, which persisted into late AD stages. Interestingly, MS GABAergic projections developed a series of adaptive strategies to combat DG interneuron hyperactivity. During early-stage AD, MS-DG GABAergic projections exhibit increased inhibitory synaptic strength onto DG interneurons to inhibit their activities. During late-stage AD, MS-DG GABAergic projections form higher anatomical connectivity with DG interneurons and exhibit aberrant outgrowth to increase the inhibition onto DG interneurons., Conclusion: We report the structural and functional remodeling of the MS-DG GABAergic circuit during disease progression in 3xTg-AD mice. Dynamic MS-DG GABAergic circuit remodeling represents a compensatory mechanism to combat DG interneuron hyperactivity induced by reduced GABA transmission., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Two-dimensional covalent organic frameworks (2D COFs) are promising for gas sensing owing to the large surface area, abundant active sites, and their semiconducting nature. However, 2D COFs are usually produced in the form of insoluble micro-crystallites. Their poor contacts between grain boundaries severely suppress the conductivity, which are too low for chemresistive gas sensing. Here, we demonstrate that halide perovskites can be employed as electric glues to bond 2D COF crystallites to improve their conductivity by two orders of magnitude, activating them to detect NO 2 with high selectivity and sensitivity. Resonant microcantilever, grand canonical Monte Carlo, density functional theory and sum-frequency generation analyses prove that 2D COFs can enrich and transfer electrons to NO 2 molecules, leading to increased device conductivity. This work provides a facile approach for improving the conductivity of polycrystalline 2D COF films and may expand their applications in semiconductor devices, such as sensors, resistors, memristors and field-emission transistors., (© 2023. The Author(s).)

Context: The influences of diabetes duration and glycemic control and their potential interplays on the risk of heart failure (HF) remain unclear., Objective: This work aimed to investigate the association of diabetes duration and glycemic control with the risk of HF., Methods: A total of 23 754 individuals with diabetes but without HF during the baseline recruitment of UK Biobank were included in this study. Duration of diabetes was self-reported, and the status of glycemic control was reflected by glycated hemoglobin A1c (HbA1c) levels. Their associations with incident HF were assessed using multivariate Cox models adjusting for traditional risk factors., Results: Duration of diabetes and HbA1c levels both were positively associated with the risk of HF. The hazard ratios (HRs) (95% CI) for diabetes durations of 5 to less than 10, 10 to less than 15, and 15 years or more were 1.09 (0.97-1.23), 1.13 (0.97-1.30), and 1.32 (1.15-1.53), respectively (vs < 5 years); and the HRs for HbA1c of 53.0 to less than 58.5 mmol/mol (7.0% to < 7.5%), 58.5 to less than 63.9 mmol/mol (7.5% to < 8.0%), and 63.9 mmol/mol or greater (8.0%) were 1.15 (1.02-1.31), 1.07 (0.91-1.26), and 1.46 (1.30-1.65), respectively (vs < 53.0 mmol/mol [7.0%]). Individuals with the longest disease duration (≥ 15 years) and poorer glycemic control (HbA1c ≥ 63.9 mmol/mol [8.0%]) had a particularly higher risk of HF (P for interaction = .026)., Conclusion: The risk of HF among individuals with diabetes increases with a longer duration of diabetes and increasing HbA1c levels. This finding may contribute to the individualized prevention of HF in patients with diabetes if being considered in clinical practices and policy-making., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Numerous studies have suggested that age at first birth (AFB) is inversely associated with metabolic diseases, but positively associated with liver cancer in women. Non-alcoholic fatty liver disease (NAFLD) is a canonical example of metabolic dysfunction and inflammation-based liver disease, while the association between AFB and the risk of NAFLD remains unclear. We aimed to investigate the association between AFB and the odds of NAFLD in women., Methods: Women older than 20 years at the time of the survey were analyzed using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018 in the US. AFB was obtained with self-administered questionnaires. NAFLD was diagnosed as fatty liver index (FLI) ≥ 60. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression models., Results: Of the 12,188 women included in this study, 5670 (46.5%) had NAFLD. Compared to individuals with AFB of 30-32 years old (reference group), the fully adjusted ORs and 95% CI in women with AFB < 18, 18-20, 21-23, and 24-26 years were 1.52 (95% CI 1.14, 2.03), 1.60 (95% CI 1.21, 2.11), 1.40 (95% CI 1.06, 1.84), and 1.33 (95% CI 1.01-1.76), respectively. Yet there was no significant difference between AFB of 27-29, 33-35, or > 35 years compared to the reference group., Conclusions: Women with younger AFB have higher odds of NAFLD in later life. Policymakers should consider focusing on those with earlier AFB for screening and prevention of NAFLD., (© 2022. Asian Pacific Association for the Study of the Liver.)

Purpose: This meta-analysis was designed for examining the relative clinical safety and efficacy of normal stent (NS) and radioactive stent (RS) insertion in malignant hilar obstruction (MHO) patients., Material and Methods: Relevant studies published as of March 2022 were identified through searches of the Medline, Embase, Wanfang, and CNKI databases, and the pooled results of these studies were then analyzed., Results: Eight studies including 258 and 247 patients that underwent NS and RS insertion, respectively, were incorporated into this meta-analysis. RS insertion was found to be associated with significant improvements in functional successful rate ( p  = 0.04), Δaspertate aminotransferase (AST, p  = 0.0004), Δalanine aminotransferase (ALT, p  = 0.002), stent patency ( p  < 0.00001), stent re-obstruction rate ( p  = 0.03), and OS ( p  < 0.00001) outcomes as compared to those associated with NS insertion. No differences in Δtotal bilirubin (TBIL, p  = 0.38), cholangeitis rate ( p  = 0.45), cholecystitis rate ( p  = 0.84), or hemorrhage rate ( p  = 0.87) were observed when comparing patients that underwent RS and NS insertion. Substantial publication bias was observed for endpoints of cholecystitis and hemorrhage., Conclusions: These results suggest that relative to NS insertion, RS insertion can effectively prolong stent patency and OS in MHO cases.

Long non-coding RNAs (lncRNAs), a class of transcripts exceeding 200 nucleotides and lacking protein coding potential, have been proven to play important roles in viral infection and host immunity. Bombyx mori nucleopolyhedrovirus (BmNPV) is an important pathogen, which causes the silkworm disease and leads to a huge challenge to the sericultural industry. At present, research on the roles of insect lncRNAs in host-virus interaction are relatively few. In this study, we explored the function of lincRNA&#95;XR209691.3 that was significantly up-regulated in the silkworm fat body upon BmNPV infection. Firstly, the subcellular localization experiment confirmed that lincRNA&#95;XR209691.3 was present in both the nucleus and cytoplasm. Enhancing the expression of lincRNA&#95;XR209691.3 in BmN cells could promote the proliferation of BmNPV, while inhibition of lincRNA&#95;XR209691.3 by RNA interference suppresses the proliferation of BmNPV. Combining RNA pull-down and mass spectrometry, we identified the host and BmNPV proteins that could interact with lincRNA&#95;XR209691.3. Next, by using truncation experiment and RNA immunoprecipitation (RIP) assay, it was found that lincRNA&#95;XR209691.3 could bind to the Actin domain of BmHSP70. Subsequently, overexpression of lncRNA&#95;XR209691.3 in BmN cells promoted the expression of BmHSP70, while knockdown of BmHsp70 suppressed the replication of BmNPV. Based on the above results, it is speculated that lincRNA&#95;XR209691.3 could promote the proliferation of BmNPV through interaction with BmHSP70, possibly by improving the stability of BmHSP70 and thereby enhancing the expression of BmHSP70. Our results shed light on the lncRNA function in insect-pathogen interactions and provide a new clue to elucidate the molecular mechanism of BmNPV infection., (© 2022 Royal Entomological Society.)

Introduction: This systematic review and meta-analysis aimed to assess the efficacy and safety of cupping therapy in patients with metabolic syndrome (MetS)., Methods: This systematic review focused on patients with MetS and included randomized controlled trials (RCTs) that compared the effects of cupping therapy with control groups. A total of 12 electronic databases were searched from inception until February 03, 2023. The main outcome after the meta-analysis was waist circumference; the others included anthropometric variables, blood pressure, lipid profile, fasting blood glucose level, and high-sensitivity C-reactive protein level. The incidence of adverse events and the follow-up courses were also evaluated. Risk of bias (ROB) was evaluated using ROB 2.0 from the Cochrane Handbook., Results: This systematic review included five studies involving 489 patients. Some risks of bias were also identified. The meta-analysis revealed a statistically significance in waist circumference (MD = -6.07, 95% CI: -8.44 to -3.71, P < .001, I2 = 61%, τ2 = 3.4), body weight (MD = -2.46, 95% CI: -4.25 to -0.68, P = .007, I2 = 0%, τ2 = 0) and body mass index (MD = -1.26, 95% CI: -2.11 to -0.40, P = .004, I2 = 0%, τ2 = 0) between the cupping therapy and control groups. However, there were no significant results in total fat percentage and blood pressure values. Regarding biochemical markers, cupping significantly lowered the concentration of low-density lipoprotein cholesterol (MD = -3.98, 95% CI: -6.99 to -0.96, P = .010, I2 = 0%, τ2 = 0) but had no significant effect on total cholesterol, triglyceride, high-density lipoprotein cholesterol, fasting blood glucose, and high-sensitivity C-reactive protein. 3 RCTs reported no adverse events., Conclusions: Despite some ROB and low to substantial heterogeneity of the included studies, cupping therapy can be considered a safe and effective complementary intervention for reducing waist circumference, body weight, body mass index, and low-density lipoprotein cholesterol in patients with MetS. In the future, well-designed, high-quality, rigorous methodology, and long-term RCTs in this population are required to assess the efficacy and safety of cupping therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Fiber-optic sensors are an indispensable element of modern sensing technologies by virtue of their low cost, excellent electromagnetic immunity, and remote sensing capability. Optical Vernier effect is widely used to enhance sensitivity of fiber-optic sensors but requires bulky and complex cascaded interferometers. Here we propose and experimentally demonstrate an ultracompact (∼2 mm by ∼2 mm) Vernier-effect-improved sensor by only using a single microfiber-knot resonator. With the Vernier effect achieved by controlling the optical beating with the spectral ripple of a super light emitting diode (SLED), we show ∼20x sensitivity enhancement for quantitative temperature monitoring. Our sensor creates a new practical method to realize Vernier effect in fiber-optic sensors and beyond.

PD-L1 localized to immunosuppressive small extracellular vesicles (sEV PD-L1) contributes to tumor progression and is associated with resistance to immune-checkpoint blockade (ICB) therapy. Here, by establishing a screening strategy with a combination of tissue microarray (TMA), IHC staining, and measurement of circulating sEV PD-L1, we found that the endosomal sorting complex required for transport (ESCRT) member protein hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) was the key regulator of circulating sEV PD-L1 in head and neck squamous cell carcinoma (HNSCC) patients. Increased HRS expression was found in tumor tissues and positively correlated with elevated circulating sEV PD-L1 in patients with HNSCC. The expression of HRS was also negatively correlated to the infiltration of CD8+ T cells. Knockdown of HRS markedly reduced PD-L1 expression in HNSCC cell-derived sEVs, and these sEVs from HRS knockdown cells showed decreased immunosuppressive effects on CD8+ T cells. Knockout of HRS inhibited tumor growth in immunocompetent mice together with PD-1 blockade. Moreover, a higher HRS expression was associated with a lower response rate to anti-PD-1 therapy in patients with HNSCC. In summary, our study reveals HRS, the core component of ESCRT-0, regulates sEV PD-L1 secretion, and is associated with the response to ICB therapy in patients with HNSCC, suggesting HRS is a promising target to improve cancer immunotherapy., (©2022 American Association for Cancer Research.)

Introduction: Neonatal hyperbilirubinemia is common and remains a clinical concern in China. Since neonatal hyperbilirubinemia is linked to genetic factors, we aimed to identify the gene variants of the red blood cell membrane (RBCM) and evaluate the clinical risk factors in Chinese neonates with hyperbilirubinemia., Methods: 117 hyperbilirubinemia neonates (33 cases of moderate hyperbilirubinemia and 84 cases of severe hyperbilirubinemia) and 49 controls with normal bilirubin levels were selected as our study subjects. A customized 22-gene panel with next-generation sequencing (NGS) was designed to characterize genetic variations among the neonates. Sanger sequencing was used to verify the accuracy of the NGS. The clinical risk factors and potential effects of genetic variations in neonates with hyperbilirubinemia were subsequently assessed., Results: After data filtering, suspected pathogenic variants of UGT1A1, SLCCO1B1, and RBCM-associated gene were identified in neonates, the combined numbers of RBCM-associated gene variants were found to have differences between the hyperbilirubinemia group and the controls (p = 0.008), they were also different between severe hyperbilirubinemia and moderate hyperbilirubinemia (p = 0.008), and were correlated with an increased risk of hyperbilirubinemia (odds ratio = 9.644, p = 0.006). The UGT1A1-rs4148323 variant in neonates with hyperbilirubinemia was significantly increased as compared with the controls (p < 0.001). However, there was no statistical difference for the SLCO1B1-rs2306283 variant between the hyperbilirubinemia group and the controls. In addition, breastfeeding contributed to an increased risk of hyperbilirubinemia., Conclusion: Our study highlights that the RBCM-related gene variants are an underestimated risk factor, which may play an important role in developing hyperbilirubinemia in Chinese newborns., (© 2023 S. Karger AG, Basel.)

Background: This study aimed to investigate the influence of a variant of the UGT1A1 gene on the occurrence and severity of prolonged jaundice in Chinese infants at term., Methods: 175 infants with prolonged jaundice and 149 controls were used in this retrospective case-control study. The infants with prolonged jaundice were subdivided into the mild-medium and severe jaundice groups (TSB ≥ 342 µmol/L). The frequency and genotype distribution of the UGT1A1 and G6PD genes, and clinical parameters including sex, birth weight, delivery mode, gestational age, and feeding mode, were analyzed, and the differences in the parameters between the two groups were compared., Results: The allele frequency of UGT1A1*6 in the prolonged jaundice group was higher than that in the control group. Similarly, it was also higher in the severe jaundice group than in the mild-medium jaundice group. Homozygous and heterozygous UGT1A1*6 were also found more frequently in the prolonged jaundice group than in the control group. Exclusive breastfeeding, homozygous and heterozygous forms of UGT1A1*6 were significant risk indicators for prolonged jaundice. Moreover, UGT1A1*6 was the best predictor of prolonged severe jaundice., Conclusion: UGT1A1*6 appears to be a risk factor for prolonged jaundice with hyperbilirubinemia in term infants of Chinese ancestry who are exclusively breastfed., 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., (© 2022 Yang, Lin, Xu, Yang, Wu, Chen, Xie, Huang, Lin, Wu, Ma, Li and Yang.)

Rapid eye movement (REM) sleep disturbances are prevalent in various psychiatric disorders. However, the neural circuits that regulate REM sleep remain poorly understood. Here, we found that in male mice, optogenetic activation of rostromedial tegmental nucleus (RMTg) GABAergic neurons immediately converted REM sleep to arousal and then initiated non-REM (NREM) sleep. Conversely, laser-mediated inactivation completely converted NREM to REM sleep and prolonged REM sleep duration. The activity of RMTg GABAergic neurons increased to a high discharge level at the termination of REM sleep. RMTg GABAergic neurons directly converted REM sleep to wakefulness and NREM sleep via inhibitory projections to the laterodorsal tegmentum (LDT) and lateral hypothalamus (LH), respectively. Furthermore, LDT glutamatergic neurons were responsible for the REM sleep-wake transitions following photostimulation of the RMTg GABA -LDT circuit. Thus, RMTg GABAergic neurons are essential for suppressing the induction and maintenance of REM sleep., (© 2022. The Author(s).)

Physiological rapid eye movement (REM) sleep termination is vital for initiating non-REM (NREM) sleep or arousal, whereas the suppression of excessive REM sleep is promising in treating narcolepsy. However, the neuronal mechanisms controlling REM sleep termination and keeping sleep continuation remain largely unknown. Here, we reveal a key brainstem region of GABAergic neurons in the control of both physiological REM sleep and cataplexy. Using fiber photometry and optic tetrode recording, we characterized the dorsal part of the deep mesencephalic nucleus (dDpMe) GABAergic neurons as REM relatively inactive and two different firing patterns under spontaneous sleep-wake cycles. Next, we investigated the roles of dDpMe GABAergic neuronal circuits in brain state regulation using optogenetics, RNA interference technology, and celltype-specific lesion. Physiologically, dDpMe GABAergic neurons causally suppressed REM sleep and promoted NREM sleep through the sublaterodorsal nucleus and lateral hypothalamus. In-depth studies of neural circuits revealed that sublaterodorsal nucleus glutamatergic neurons were essential for REM sleep termination by dDpMe GABAergic neurons. In addition, dDpMe GABAergic neurons efficiently suppressed cataplexy in a rodent model. Our results demonstrated that dDpMe GABAergic neurons controlled REM sleep termination along with REM/NREM transitions and represented a novel potential target to treat narcolepsy., (© 2022. The Author(s).)

Mounting evidence indicates that tumor-derived exosomes (TDEs) play critical roles in tumor development and progression by regulating components in the tumor microenvironment (TME) in an autocrine or paracrine manner. Moreover, due to their delivery of critical molecules that react to chemotherapy and immunotherapy, TDEs also contribute to tumor drug resistance and impede the effective response of antitumor immunotherapy, thereby leading to poor clinical outcomes. There is a pressing need for the inhibition or removal of TDEs to facilitate the treatment and prognosis of cancer patients. Here, in the present review, we systematically overviewed the current strategies for TDE inhibition and clearance, providing novel insights for future tumor interventions in translational medicine. Moreover, existing challenges and potential prospects for TDE-targeted cancer therapy are also discussed to bridge the gaps between progress and promising applications., (© 2022. The Author(s).)

Objective: This study investigated the composition of pathogenic microorganisms, clinical features, and therapeutic strategies of infective artery rupture of renal allografts in recipients receiving deceased donor (DD) kidneys., Methods: We retrospectively studied the clinical data of the DD kidney transplant recipients with donor-associated infection at Tongji Hospital, Wuhan, China from January 1, 2015 to December 31, 2018, related recipients and corresponding donors. We collected the entire results of pathogenic microorganisms cultured from these related ruptured kidneys and then analyzed their distribution and differences., Results: A total of 1440 kidney transplants from DD were performed in our center. The total incidence of infective artery rupture in kidney transplants was about 0.76% (11/1440), and the annual incidence ranged from 0.25% to 1.03%. The microbial culture results revealed that 11 recipients suffered from infective artery rupture and 3 recipients who accepted the kidney from same donor had the donor-associated pathogens, including 9 fungal strains (28.1%) and 23 bacterial strains (71.9%). There were 4 recipients infected with multi-drug-resistant Staphylococcus and Klebsiella pneumoniae from the above 11 recipients, of which, 10 recipients underwent graft loss, and one died of septic shock. The microbial cultures of the remaining 3 recipients who received appropriate anti-infective regimens turned negative eventually, and the patients were discharged successfully without significant complications., Conclusion: Renal recipients with infections derived from DDs were at high risk of artery rupture, graft loss, or even death. Appropriate anti-infective treatment is essential to reduce the incidence of artery rupture and mortality., (© 2022. Huazhong University of Science and Technology.)

Long non-coding RNA (lncRNA) is a type of non-coding RNA molecule, which exceeds 200 nucleotides in length and participates in the regulation of a variety of life activities. Recent studies showed that lncRNAs play important roles in viral infection and host immunity. At present, the researches on insect lncRNAs are relatively few. In this study, we found the expression of Lnc&#95;209997 was significantly down-regulated in silkworm fat body infected with Bombyx mori nucleopolyhedrosis virus (BmNPV). Inhibition of Lnc&#95;209997 promoted BmNPV replication. Enhancing the expression of Lnc&#95;209997 inhibited the proliferation of BmNPV. miR-275-5p was up-regulated in silkworm fat body infected with BmNPV. Dual luciferase reporter gene system confirmed the interaction between Lnc&#95;209997 and miR-275-5p. Over-expression of Lnc&#95;209997 inhibited the expression of miR-275-5p, while inhibition of Lnc&#95;209997 enhanced the expression of miR-275-5p. Further, over-expression of miR-275-5p can facilitate the replication of BmNPV. These results suggested that BmNPV could increase the expression of miR-275-5p by inhibiting cellular Lnc&#95;209997 expression to promote their own proliferation. Our results are helpful for better understanding the role of lncRNAs in BmNPV infection, and provide insights into elucidating the molecular mechanism of interaction between Bombyx mori and virus., (© 2022 Royal Entomological Society.)

Introduction: Both side-by-side (SBS) and stent-in-stent (SIS) bilateral stenting have been used for patients with malignant hilar biliary obstruction (MHBO). However, it is unclear which technique is better., Aim: This meta-analysis is conducted to investigate the clinical efficacy and safety of SBS and SIS bilateral stenting for patients with MHBO., Material and Methods: Relevant studies were searched in PubMed, Embase, Cochrane Library, Wanfang, VIP, and CINK databases. The timeline for the searches was from the establishment of the database to September 2021. The relative outcomes are pooled., Results: A total of 7 studies fulfilled the inclusion criteria and entered into this meta-analysis. The pooled technical success rate was significant higher in the SIS group than that in the SBS group (p = 0.04). The pooled early complication rate was significantly lower in the SIS group than in the SBS group (p = 0.04). The pooled stent re-obstruction rate was significantly lower in the SBS group than in the SIS group (p = 0.04). The pooled stent patency duration was significantly longer in the SBS group than in the SIS group (p = 0.01). The pooled functional success rates (p = 0.79), total complication rates (p = 0.34), and overall survival duration (p = 0.27) were comparable between 2 groups. Egger test did not show any publication bias., Conclusions: When comparing the SBS and SIS bilateral stenting for patients with MHBO, although SIS technique may have the superiorities of technical success and early complication rates, the longer stent patency was achieved by the SBS technique., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Fundacja Videochirurgii.)

Measuring residual aberrations up to second order using a crystalline specimen in transmission electron microscope is challenging. Here, we show by good examples of both experimental and simulated images that it is feasible to measure aberrations up to the second-order, using minimum amplitude contrast criterion for the exit wave function reconstructed. We propose a two-steps strategy for the task: (i) Firstly measuring defocus and two-fold astigmatism simultaneously to avoid error accumulation and to reduce the number of dimensions in parameters space. (ii) Then, with minimized misleading effects (or errors) in defocus and two-fold astigmatism, estimations of three-fold astigmatism and coma can be conducted more efficiently and effectively. Influences of other factors such as specimen structure, resolution and specimen thickness on the validity of the method are also discussed in detail. Our study provides a practical procedure for correcting residual aberrations in image wave using crystalline materials, which can then facilitate application of exit wave reconstruction technique to materials research., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Antibody-mediated rejection (AMR) is one of the major causes of graft loss after transplantation. Recently, the regulation of B cell differentiation and the prevention of donor-specific antibody (DSA) production have gained increased attention in transplant research. Herein, we established a secondary allogeneic in vivo skin transplant model to study the effects of romidepsin (FK228) on DSA. The survival of grafted skins was monitored daily. The serum levels of DSA and the number of relevant immunocytes in the recipient spleens were evaluated by flow cytometry. Then, we isolated and purified B cells from B6 mouse spleens in vitro by magnetic bead sorting. The B cells were cultured with interleukin-4 (IL-4) and anti-clusters of differentiation 40 (CD40) antibody with or without FK228 treatment. The immunoglobulin G1 (IgG1) and IgM levels in the supernatant were evaluated by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the corresponding levels of messenger RNA (mRNA) and protein expression in cultured cells and the recipient spleens. The results showed that FK228 significantly improved the survival of allogeneic skin grafts. Moreover, FK228 inhibited DSA production in the serum along with the suppression of histone deacetylase 1 (HADC1) and HDAC2 and the upregulation of the acetylation of histones H2A and H3. It also inhibited the differentiation of B cells to plasma cells, decreased the transcription of positive regulatory domain-containing 1 ( Prdm 1) and X-box-binding protein 1 ( Xbp1 ), and decreased the expression of phosphorylated inositol-requiring enzyme 1 α (p-IRE1α), XBP1, and B lymphocyte-induced maturation protein-1 (Blimp-1). In conclusion, FK228 could decrease the production of antibodies by B cells via inhibition of the IRE1α-XBP1 signaling pathway. Thus, FK228 is considered as a promising therapeutic agent for the clinical treatment of AMR.

Bombyx mori nuclear polyhedrosis virus (BmNPV) is one of several viruses that cause great harm to the sericulture industry, and its pathogenic mechanism is still being explored. Geldanamycin (GA), a kind of HSP90 inhibitor, has been verified to suppress BmNPV proliferation. However, the molecular mechanism by which GA inhibits BmNPV is unclear. MicroRNAs (miRNAs) have been shown to play a key role in regulating virus proliferation and host-pathogen interactions. In this study, BmN cells infected with BmNPV were treated by GA and DMSO for 72 h, respectively, then transcriptome analysis of miRNA was performed from the GA group and the control group. As a result, a total of 29 miRNAs were differentially expressed (DE), with 13 upregulated and 16 downregulated. Using bioinformatics analysis, it was found that the target genes of DEmiRNAs were involved in ubiquitin-mediated proteolysis, phagosome, proteasome, endocytosis pathways, and so on. Six DEmiRNAs were verified by quantitative reverse-transcription polymerase chain reaction. DElong noncoding RNA (DElncRNA)-DEmiRNA-messenger RNA (mRNA) regulatory networks involved in apoptosis and immune pathways were constructed in GA-treated BmN cells, which included 12 DEmiRNA, 132 DElncRNA, and 69 mRNAs. This regulatory network enriched the functional role of miRNA in the BmNPV-silkworm interactions and improved our understanding of the molecular mechanism of HSP90 inhibitors on BmNPV proliferation., (© 2022 Wiley Periodicals LLC.)

Adult hippocampal neurogenesis plays a critical role in memory and emotion processing, and this process is dynamically regulated by neural circuit activity. However, it remains unknown whether manipulation of neural circuit activity can achieve sufficient neurogenic effects to modulate behavior. Here we report that chronic patterned optogenetic stimulation of supramammillary nucleus (SuM) neurons in the mouse hypothalamus robustly promotes neurogenesis at multiple stages, leading to increased production of neural stem cells and behaviorally relevant adult-born neurons (ABNs) with enhanced maturity. Functionally, selective manipulation of the activity of these SuM-promoted ABNs modulates memory retrieval and anxiety-like behaviors. Furthermore, we show that SuM neurons are highly responsive to environmental novelty (EN) and are required for EN-induced enhancement of neurogenesis. Moreover, SuM is required for ABN activity-dependent behavioral modulation under a novel environment. Our study identifies a key hypothalamic circuit that couples novelty signals to the production and maturation of ABNs, and highlights the activity-dependent contribution of circuit-modified ABNs in behavioral regulation., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To investigate the effects and mechanisms of equol and its enantiomers on urethane-induced lung cancer in mice., Methods: A total of 120 5-week-old male C57BL/6 mice were randomly divided into 8 groups: lung cancer tumor control group (CG), genistein control group (GCG), low dose racemic equol group (LEG), high dose racemic equol group (HEG), low dose R-equol group (LRE), high dose R-equol group (HRE), low dose S-equol group (LSE) and high dose S-equol group (HSE). Urethane was injected subcutaneously twice a week for 4 weeks to induce lung cancer and then the mice were fed for 4 months. The body weight and food intake of each group were measured and recorded weekly. After the mice were sacrificed, the blood, livers and lungs of the mice were collected. The incidence of lung cancer in each group was recorded. The concentration of serum superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxydeoxygunosine (8-OHdG) were detected by the corresponding kits. Western blotting was used to detect the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the livers. Between-group differences in body weight and food intake of the mice were compared using repeated measures ANOVA, and ANOVA for the differences between non-repeated measurements, with post hoc analysis using Tukey's method if there were between-group differences. Comparisons of categorical data were performed by chi-square test, and if there were differences between the groups, the Bonferroni method was used for pairwise comparison., Results: A total of 49 in the 120 mice developed lung cancer. The overall incidence of lung cancer was 40.8%. Compared with the control group, the incidence of lung cancers in each experimental group was lower, and the difference was statistically significant. The incidence of lung cancer in the high-dose experimental group was significantly lower than that in the low-dose experimental group. However, the incidence of lung cancer was similar in the three equol groups and the genistein group at the same dose. Compared with the control group, the high-dose experimental group had higher serum SOD concentration, lower MDA and 8-OHdG concentrations, and the differences were statistically significant. Western blotting analysis showed that the expression levels of Nrf2 protein in the experimental groups were higher than those in the control group except the low-dose racemic equol group, and the Nrf2 protein expression level in the high-dose equol groups was higher than that in the low-dose equol groups., Conclusion: Racemic equol and its enantiomers mayinhibit lung carcinogenesis through antioxidant effects.