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Covalent Organic Frameworks (COFs) emerged as versatile materials with promising potential in  biomedicine. Their customizable functionalities and tunable pore structures make them valuable for various biomedical applications such as biosensing, bioimaging, antimicrobial activity, and targeted drug delivery. Despite efforts made to create nanoscale COFs (nCOFs) to enhance their interaction with biological systems, a comprehensive understanding of their inherent biological activities remains a significant challenge. In this study, a thorough investigation is conducted into the biocompatibility and anti-neoplastic properties of two distinct imine-based nCOFs. The approach involved an in-depth analysis of these nCOFs through in vitro experiments with various cell types and in vivo assessments using murine models. These findings revealed significant cytotoxic effects on tumor cells. Moreover, the activation of multiple cellular death pathways, including apoptosis, necroptosis, and ferroptosis is determined, supported by evidence at the molecular level. In vivo evaluations exhibited marked inhibition of tumor growth, associated with the elevated spontaneous accumulation of nCOFs in tumor tissues and the modulation of cell death-related protein expression. The research contributes to developing a roadmap for the characterization of the intricate interactions between nCOFs and biological systems and opens new avenues for exploiting their therapeutic potential in advanced biomedical applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Engineering Kondo lattice with tailored functionality is desirable for elucidating the heavy fermion physics. We realize the construction of an artificial Kondo lattice/superconductor heterojunction by growing monolayer VSe 2 on bulk 2H-NbSe 2 with molecular beam epitaxy. Spectroscopic imaging scanning tunneling microscopy measurements show the emergence of a new charge density wave (CDW) phase with 3 × 3 periodicity on the monolayer VSe 2 . Unexpectedly, a pronounced Kondo resonance appears around the Fermi level, and distributes uniformly over the entire film, evidencing the formation of Kondo lattice. Density functional theory calculations suggest the existence of magnetic interstitial V atoms in VSe 2 /NbSe 2 , which play a key role in forming the CDW phase along with the Kondo lattice observed in VSe 2 . The Kondo origin is verified from both the magnetic field and temperature dependences of the resonance peak, yielding a Kondo temperature of ~ 44 K. Moreover, a superconducting proximity gap opens on monolayer VSe 2 , whose shape deviates from the function of one-band BCS superconductor, but is reproduced by model calculations with heavy electrons participating the pairing condensate. Our work lays the experimental foundation for studying interactions between the heavy fermion liquids and the superconducting condensate., (© 2024. The Author(s).)

In order to solve the problem of poor sensitivity and selectivity of conventional SERS substrates, we synthesized Mo 1-x W x S 2 @Ag 2 S nanosheets in this paper by a two-step hydrothermal method. The structure and morphology of the synthesized Mo 1- x W x S 2 @Ag 2 S nanosheets were characterized by XRD and SEM,respectively. The results show that the Mo 1- x W x S 2 @Ag 2 S nanosheet has an irregular layered structure. Further, the SERS properties of Mo 1- x W x S 2 @Ag 2 S nanosheets were tested by using rhodamine 6G (R6G), crystalline violet (CV), and 4-mercaptobenzoic acid (4-MBA) as probe molecules, respectively. The test results demonstrated that the nanosheets were specific to R6G and CV probe molecules, and the mechanism of selectivity was due to CT enhancement. In addition, Mo 1- x W x S 2 @Ag 2 S exhibits ultrahigh sensitivity in R6G and CV, with the corresponding detection limit of both reached 10 -8 M. And linear fitting of the peak intensities was carried out, with the R 2 coefficient of 0.981 and 0.951, respectively. Finally, the relative standard deviations (RSDs) of this Mo1-xWxS2@Ag2S nanosheets was obtained to be 8.56 % by test 1 × 10 -4 M R6G at the characteristic peak 613 cm -1 , which represents excellent detection repeatability. The Mo 1- x W x S 2 @Ag 2 S nanosheets are rich in edge-active sites favorable for charge transfer, which can enhance the SERS signals of the target molecules better. Besides, the Raman detection of the surface of Mo 1- x W x S 2 @Ag 2 S nanosheets using nitrofurantoin (NFT) also reached a detection limit of 10 -8 M. Mo 1- x W x S 2 @Ag 2 S nanosheets substrates can find applications in medicine and provide new strategies for improving the SERS performance., 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.)

Non-viral gene delivery with cationic polymers/nanoparticles relies on iterative optimization of the carrier to achieve delivery. Here we demonstrate, instead, that precision engineering of cell surfaces to covalently capture a polyplex accelerates gene delivery within just 10 min of exposure. Azides were installed into cell-surface sialic acids, which enabled the rapid and selective recruitment of cyclooctyne-functional polyplexes, leading to increased delivery of fluorescent cargo, and also increased plasmid expression and siRNA knockdown. Covalent delivery enhancement was also shown for a polymer-coated nanoparticle delivery system. This validates using cellular metabolic engineering (or other synthetic biology) tools to overcome payload delivery challenges., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at -80 °C consumes as much energy per day as a small household 1 . Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose 2 , sucrose or polymers 3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze-thaw 4 , leading to a very complex and expensive supply chain. Other ideas involve ensilication 5 and chemical modification of proteins 6 . In short, protein stabilization is a challenge with no universal solution 7,8 . Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide., (© 2024. The Author(s).)

TGFBR2, a key regulator of the TGFβ signaling pathway, plays a crucial role in gastric cancer (GC) metastasis through its endosomal recycling process. Despite its importance, the mechanisms governing this process remain unclear. Here, we identify integrin β5 (ITGB5) as a critical mediator that promotes TGFBR2 endosomal recycling. Our study reveals elevated expression of ITGB5 in GC, particularly in metastatic cases, correlating with poor patient outcomes. Knockdown of ITGB5 impairs GC cell metastasis both in vitro and in vivo. Mechanistically, ITGB5 facilitates epithelial-mesenchymal transition mediated by TGFβ signaling, thereby enhancing GC metastasis. Acting as a scaffold, ITGB5 interacts with TGFBR2 and SNX17, facilitating SNX17-mediated endosomal recycling of TGFBR2 and preventing lysosomal degradation, thereby maintaining its surface distribution on tumor cells. Notably, TGFβ signaling directly upregulates ITGB5 expression, establishing a positive feedback loop that exacerbates GC metastasis. Our findings shed light on the role of ITGB5 in promoting GC metastasis through SNX17-mediated endosomal recycling of TGFBR2, providing insights for the development of targeted cancer therapies., 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. Published by Elsevier B.V.)

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pregnant women with chronic hepatitis B (CHB) exhibit unique clinical features in terms of postpartum immune system reconstitution and recovery from pregnancy-related changes. However, current studies focus primarily on the outcomes of maternal-infant transmission and postpartum hepatitis flares. We aimed to evaluate the profiles of hepatitis B core-related antigen (HBcrAg) and pregenomic RNA (pgRNA) in pregnant women with CHB., Methods: This retrospective analysis included treatment-naïve pregnant women with CHB who were followed up regularly in an outpatient clinic from 2014 to 2021. Baseline HBcrAg and pgRNA levels were compared in patients with different disease phases. Changes in these parameters were examined in a subset of patients receiving antiviral prophylaxis. HBcrAg and pgRNA levels were measured before treatment, at 32 weeks of gestation, and postpartum., Results: The final analysis included a total of 121 patients, 100 of whom were hepatitis B e antigen (HBeAg)-positive (96 and 4 in the immune-tolerant and -indeterminate phases, respectively) and 21 of whom were HBeAg-negative (6 and 15 in the immune-active and -inactive carrier phases, respectively). The HBeAg-negative group vs the HBeAg-positive group had lower levels of baseline HBcrAg (median [interquartile range {IQR}], 3.7 [3.0-5.9] vs 8.6 [8.4-8.7] log 10 U/mL; P < .01) and pgRNA (median [IQR], 0.0 [0.0-2.5] vs 7.8 [7.6-8.1] log 10 copies/mL; P < .01). The serum levels of HBcrAg and pgRNA were highest in immune-tolerant carriers and lowest in immune-inactive carriers. In HBeAg-positive patients, the correlation coefficients of HBcrAg and pgRNA with hepatitis B virus (HBV) DNA were 0.40 and 0.43, respectively; in HBeAg-negative patients, they were 0.53 and 0.51, respectively (all P < .05). The correlation coefficients with hepatitis B surface antigen (HBsAg) were 0.55 and 0.52 ( P < .05) in HBeAg-positive patients, respectively, while in HBeAg-negative patients they were 0.42 and 0.37, respectively ( P > .05). Among 96 patients receiving antiviral prophylaxis, we detected a rapid decrease in HBV DNA to an undetectable level during treatment but relatively stable levels of pgRNA and HBcrAg., Conclusions: HBcrAg and pgRNA levels are lower in HBeAg-negative patients than in HBeAg-positive patients. These 2 markers are significantly associated with HBV DNA irrespective of HBeAg status, while they are significantly associated with HBsAg only in HBeAg-positive patients., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Methamphetamine is a highly addictive psychostimulant drug that is abused globally and is a serious threat to health worldwide. Unfortunately, the specific mechanism underlying addiction remains unclear. Thus, this study aimed to investigate the characteristics of functional connectivity in the brain network and the factors influencing methamphetamine use disorder in patients using magnetic resonance imaging. We included 96 abstinent male participants with methamphetamine use disorder and 46 age- and sex-matched healthy controls for magnetic resonance imaging. Compared with healthy controls, participants with methamphetamine use disorder had greater impulsivity, fewer small-world attributes of the resting-state network, more nodal topological attributes in the cerebellum, greater functional connectivity strength within the cerebellum and between the cerebellum and brain, and decreased frontoparietal functional connectivity strength. In addition, after controlling for covariates, the partial correlation analysis showed that small-world properties were significantly associated with methamphetamine use frequency, psychological craving, and impulsivity. Furthermore, we revealed that the small-word attribute significantly mediated the effect of methamphetamine use frequency on motor impulsivity in the methamphetamine use disorder group. These findings may further improve our understanding of the neural mechanism of impulse control dysfunction underlying methamphetamine addiction and assist in exploring the neuropathological mechanism underlying methamphetamine use disorder-related dysfunction and rehabilitation., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sleep disorders, a common concern in modern society, seriously affect people's physical and mental health. Reported findings suggest that both acute exercise intervention and long-term regular exercise intervention can improve the disrupted sleep structure and normalize the duration and proportion of the different phases of sleep. Moreover, exercise intervention has a positive effect on the endocrine functions, the metabolic functions, the immune response, the autonomic nervous system, and cardiac functions during sleep. It is a non-medicative therapeutic strategy for improving sleep disorders. The specific type of exercise intervention (aerobic exercise, resistance exercise, or meditative movement) adopted is one of the moderating variables of exercise intervention programs. Different types of exercise improve sleep disorders by way of different mechanisms. Exercise volume and intensity are another moderating variable of exercise intervention programs. The optimal amount and intensity of exercise for different individuals to improve sleep disorders may vary. Exercise interventions implemented at the different times throughout a day can also have varying degrees of impact on sleep disorders and there is no consensus on the optimal exercise time for improving sleep quality at present. Herein, we summarized the mechanisms by which exercise intervention improves sleep disorders from four perspectives, including epigenetics, hyperarousal, human circadian rhythm, and body temperature regulation. In addition, we discussed the current gaps and prospects of research in this field, aiming to provide a theoretical basis for the development of exercise prescriptions for sleep disorders., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Board of Journal of Sichuan University (Medical Sciences).)

Objective: This study aimed to evaluate the expression of genes involved in cholesterol metabolism and establish their association with oxidative stress (OS)., Methods: We employed an in vitro experimental design and cells were divided into six groups: C (control), CH (HepG2 + H2O2), CHN (HepG2 + H2O2 + NAC), F (FFA-treated HepG2), FH (FFA-treated HepG2 + H2O2), and FHN (FFA-treated HepG2 + H2O2 + NAC). Cell viability was assessed using the MTT assay, while successful FFA model establishment was confirmed via Oil Red staining and absorbance. Oxidative stress injury was gauged by measuring ROS, SOD activity, and MDA content. RNA transcription and protein expression of cholesterol-related (DHCR24, DHCR7) and oxidative stress-related (NFE2L2, HMOX1) genes were also examined via RT-qPCR and WB., Results: The impact of H2O2 on cell viability exhibited a time-dose-dependent pattern, paralleling the changes in reactive oxygen species (ROS) levels. Compared to the C group, FFA treatment led to an increase in Oil Red absorption and MDA content and decreased SOD activity. However, it did not result in a significant reduction in cell viability. The FH group exhibited reduced cell viability and SOD activity, along with a further elevation in MDA content compared to the F group. Furthermore, the increased SOD activity and decreased MDA content observed in the CH group were effectively reversed following NAC treatment. Such a reversal was not evident between the FHN and FH groups. Compared to the control group, genes associated with cholesterol metabolism and oxidative stress (OS) displayed heightened expression levels in the other treatment groups, with the FHN group showing lower expression levels than the FH group. Notably, changes in the protein expressions of DHCR24, DHCR7, NFE2L2, and HMOX1 were consistent and exhibited correlations., Conclusions: Cholesterol metabolism emerges as a potential mechanism underlying H2O2-induced oxidative stress injury in HepG2 cells treated with FFA.

Background: There are no standards for evaluating skin photoaging. Dermoscopy is a non-invasive detection method that might be useful for evaluating photoaging., Objective: To assess the correlation between the dermoscopic evaluation of photoaging and clinical and pathological evaluations., Methods: The age, clinical evaluation (Fitzpatrick classification, Glogau Photoaging Classification, and Chung's standardized image ruler), histopathology (Masson staining and MMP-1 immunohistochemistry), and dermoscopy (Hu's and Isik's) of 40 donor skin samples were analyzed statistically, and Spearman rank correlation analysis was performed., Results: There was a robust correlation between the total Hu scores and Isik dermoscopy. The correlation of dermoscopy with histopathology was higher than that of clinical evaluation methods. There is a strong correlation between telangiectases and lentigo. Xerosis, superficial wrinkle, diffuse erythema, telangiectases, and reticular pigmentation were significantly correlated with the three clinical evaluation methods. Superficial wrinkles were correlated with Masson, MMP-1, various clinical indicators, and other dermoscopic items., Conclusion: There is a good correlation between dermoscopy and clinical and histopathological examination. Dermoscopy might help evaluate skin photoaging., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Introduction: The COVID-19 pandemic and associated quarantine measures have precipitated a surge in mental health disorders, particularly depression and anxiety. Government policies and restrictions on physical activity have contributed to this phenomenon, as well as diminished subjective social connectedness and exacerbated objective social isolation. As two dimensions of social isolation, it is worth noting that subjectively perceived social connectedness serves as a protective factor for mental health, whereas the decline in the size of objectively evaluated social networks poses a significant risk. However, research investigating the combined influence of these two dimensions remains limited., Methods: This study used an online survey to collect data to investigate the effects of objective social connectedness and objective social networks on anxiety, stress, and depression during COVID-19 quarantine. A total of 485 participants were analyzed using statistical methods, including paired t -test, Pearson correlation analysis, linear regression, cluster analysis, ANOVA, and moderated mediated., Results: The study found that anxiety and depression scores increased during the quarantine, with age, education, and social connectedness scores associated with the increase. Pre-quarantine anxiety and depression levels were strongly correlated with mental health status during quarantine. Cluster analysis, respectively, revealed three clusters for those without increasing anxiety and depression scores. The study also found that objective social network influences the impact of subjective social connectedness on pre-quarantine mental health, which in turn affects anxiety and depression levels during quarantine., Conclusion: The study identified that quarantine increased anxiety and depression, with age being protective, and education and subjective social connectedness as risk factors. The study also emphasizes the comprehensive impact of objective and subjective social isolation. Although individuals perceive the same degree of social connectedness, those with smaller social networks are more prone to developing symptoms of anxiety and depression, which are also more likely to worsen during quarantine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Luo, Luo, Tang, Niu, Xu and Li.)

Upper confidence bound (UCB)-based contextual bandit algorithms require one to know the tail property of the reward distribution. Unfortunately, such tail property is usually unknown or difficult to specify in real-world applications. Using a tail property heavier than the ground truth leads to a slow learning speed of the contextual bandit algorithm, while using a lighter one may cause the algorithm to diverge. To address this fundamental problem, we develop an estimator (evaluated from historical rewards) for the contextual bandit UCB based on the multiplier bootstrap technique. Our proposed estimator mitigates the problem of specifying a heavier tail property by adaptively converging to the ground truth contextual bandit UCB (i.e., eliminating the impact of the specified heavier tail property) with theoretical guarantees on the convergence. The design and convergence analysis of the proposed estimator is technically nontrivial. The proposed estimator is generic and it can be applied to improve a variety of UCB-based contextual bandit algorithms. To demonstrate the versatility of the proposed estimator, we apply it to improve the linear reward contextual bandit UCB (LinUCB) algorithm resulting in our bootstrapping LinUCB (BootLinUCB) algorithm. We prove that the BootLinUCB has a sublinear regret. We conduct extensive experiments on both synthetic dataset and real-world dataset from Yahoo! to validate the benefits of our proposed estimator in reducing regret and the superior performance of BootLinUCB over the latest baseline.

Objective: Anthracycline chemotherapeutic agents have significant cardiotoxicity. The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular (LV) myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation (IVP), and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment., Methods: A total of 68 newly diagnosed breast cancer patients, who were treated with anthracycline-based chemotherapy, were analyzed. Transthoracic echocardiography was performed at baseline (T0), and after 1, 2, 3, 4 and 8 chemotherapeutic cycles (T1, T2, T3, T4 and T5, respectively). Then, the IVP, LV strain parameters [global longitudinal strain (GLS), longitudinal peak strain rate at systole (LSRs), longitudinal peak strain rate at early diastole (LSRe), longitudinal peak strain rate at late diastole (LSRa), and the E/LSRe ratio], and conventional echocardiographic parameters were obtained and further analyzed. A relative reduction of >15% in GLS was considered a marker of early LV subclinical dysfunction., Results: Compared to the T0 stage, IVP significantly increased at the T1 stage. However, there were no significant changes in GLS, LSRs, or LSRe between the T0 and T1 stages. These parameters significantly decreased from the T2 stage. LSRa started to significantly decrease at the T5 stage, and the E/LSRe ratio started to significantly increase at the T3 stage (all P<0.05). At the T0 stage, IVP (AUC=0.752, P<0.001) had a good predictive value for LV subclinical dysfunction after chemotherapy., Conclusions: IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment., (© 2023. Huazhong University of Science and Technology.)

Background: Cutaneous malignant melanoma (CMM) has the worst prognosis among skin cancers, especially metastatic CMM. Predicting its prognosis accurately could direct clinical decisions., Methods: The Surveillance, Epidemiology, and End Results database was screened to collect CMM patients' data. According to diagnosed time, patients were subdivided into three cohorts, train cohort (diagnosed between 2010 and 2013), validation cohort (diagnosed in 2014), and test cohort (diagnosed in 2015). Train cohort was used to train deep learning survival model for cutaneous malignant melanoma (DeepCMM). DeepCMM was then evaluated in train cohort and validation cohort internally, and validated in test cohort externally., Results: DeepCMM showed 0.8270 (95% CI, confidence interval, CI 0.8260-0.8280) as area under the receiver operating characteristic curve (AUC) in train cohort, 0.8274 (95% CI 0.8286-0.8298) AUC in validation cohort, and 0.8303 (95% CI 0.8289-0.8316) AUC in test cohort. Then DeepCMM was packaged into a Windows 64-bit software for doctors to use., Conclusion: Deep learning survival model for cutaneous malignant melanoma (DeepCMM) can offer a reliable prediction on cutaneous malignant melanoma patients' overall survival., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone-vessel axis in chronic kidney disease-mineral bone disorder (CKD-MBD). However, the mechanism of the bone-vessel axis in CKD-MBD remains unclear. Methods: We established a CKD-MBD rat model to observe the pathophysiological phenotype of the bone-vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone-vessel axis in CKD-MBD. Results: The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD-MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD-MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD-MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD-MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD-MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels. Conclusion: These findings provide preliminary insights into the role of ITPR2 in the bone-vessel axis in CKD-MBD. Thus, ITPR2 may be a potential target of the bone-vessel axis in CKD-MBD.

Nonsuicidal self-injury (NSSI) is associated with an increased risk of suicide. As the diagnostic criteria outlined in DSM-5 and other related clinical studies, a patient must have engaged in self-injurious behavior at least 5 times within the past year. However, patients with fewer than 5 self-injury behaviors should not be ignored. Our study included 46 adolescents aged 10-19 years with subthreshold NSSI (sNSSI), along with a control group of 50 healthy adolescents matched for age and other factors. We collected resting-state functional magnetic resonance imaging data and stool samples. The Ottawa Self-Injury Inventory and Deliberate Self-Harm Inventory were used to evaluate self-harm behaviors and addictive features. Local brain activity was assessed using fractional amplitude of low-frequency fluctuations (fALFF), and brain regions with abnormal fALFF were selected as seeds for whole-brain functional connectivity analysis. Stool samples were identified using 16S rDNA amplicon sequencing, and the LDA Effect Size method was used to explore significant differences between grouped samples. Mediation analysis was performed to investigate the brain-gut axis mechanisms of addictive features in sNSSI. We found that compared with healthy controls, sNSSI patients have abnormal fALFF in left thalamus and posterior cingulate cortex, dysconnectivities of left thalamus, and decreased Prevotellaceae. Our results suggested that addictive features of sNSSI may have a brain-gut mechanism. Furtherly, patients with 1-4 NSSI behaviors in the past year should have separate name for identification, such as "subthreshold NSSI"., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Piezoelectric nanomaterials have become increasingly popular in the field of biomedical applications due to their high biocompatibility and ultrasound-mediated piezocatalytic properties. In addition, the ability of these nanomaterials to disaggregate amyloid proteins, which are responsible for a range of diseases resulting from the accumulation of these proteins in body tissues and organs, has recently gained considerable attention. However, the use of nanoparticles in biomedicine poses significant challenges, including targeting and uncontrolled aggregation. To address these limitations, our study proposes to load these functional nanomaterials on a multifunctional mobile microrobot (PiezoBOT). This microrobot is designed by coating magnetic and piezoelectric barium titanate nanoparticles on helical biotemplates, allowing for the combination of magnetic navigation and ultrasound-mediated piezoelectric effects to target amyloid disaggregation. Our findings demonstrate that acoustically actuated PiezoBOTs can effectively reduce the size of aggregated amyloid proteins by over 80% in less than 10 minutes by shortening and dissociating constituent amyloid fibrils. Moreover, the PiezoBOTs can be easily magnetically manipulated to actuate the piezocatalytic nanoparticles to specific amyloidosis-affected tissues or organs, minimizing side effects. These biocompatible PiezoBOTs offer a promising non-invasive therapeutic approach for amyloidosis diseases by targeting and breaking down protein aggregates at specific organ or tissue sites.

Aim: To explore the change of clock gene rhythm under renal denervation (RDN) and its effect on renal function and oxidative stress during renal ischemia-reperfusion (IR) injury., Method: C57/BL6 mice were randomly divided into 4 groups at daytime 7 A M (zeitgeber time [ZT] 0) or at nighttime 7 P M (ZT12) in respectively: Sham (S) group, RDN group, IR group and RDN + IR (DIR) group. Renal pathological and functional changes were assessed by H&E staining, and serum creatinine, urea nitrogen and neutrophil gelatinase-associated lipocalin levels. Renal oxidative stress was detected by SOD and MDA levels, and renal inflammation was measured by IL-6, IL-17 A F and TNF-ɑ levels. BMAL1, CLOCK, Nrf2 and HO-1 mRNA and protein expressions were tested by qPCR and Western Blot., Result: Compared with S groups, the rhythm of BMAL1, CLOCK and Nrf2 genes in the kidney were disordered in RDN groups, while renal pathological and functional indexes did not change significantly. Compared with IR groups, renal pathological and functional indexes were significantly higher in the DIR groups, as well as oxidative stress and inflammation in renal tissues. The nocturnal IR injury in the RDN kidney was the worst while the BMAL1, Nrf2 and HO-1 expressions were the highest. In DIR groups, renal injury was aggravated after the Brusatol treatment, but there was no significant improvement after the t-BHQ treatment at night, which might be consistent with the changes of Nrf2 and HO-1 protein expressions., Conclusion: RDN lead to the disruption of BMAL1-mediated Nrf2 rhythm accumulation in the kidney, which reduced the renal ability to resist oxidative stress and inflammation, due to the impaired effect of activating Nrf2/ARE pathway in renal IR injury at nighttime., 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.)

Photoaging is unique to the skin and is accompanied by an increased risk of tumors. To explore the transcriptomic regulatory mechanism of skin photoaging, the epidermis, and dermis of 16 healthy donors (eight exposed and eight non-exposed) were surgically excised and detected using total RNA-Seq. Weighted gene co-expression network analysis (WGCNA) identified the most relevant modules with exposure. The hub genes were identified using correlation, p-value, and enrichment analysis. The critical genes were identified using Support Vector Machine-Recursive Feature Elimination (SVM-RFE) and least absolute shrinkage and selection operator (LASSO) regression, then enriched using single-gene GSEA. A competitive endogenous RNA (ceRNA) network was constructed and validated using qRT-PCR. Compared with non-exposed sites, 430 mRNAs, 168 lncRNAs, and 136 miRNAs were differentially expressed in the exposed skin. WGCNA identified the module MEthistle and 12 intersecting genes from the 71 genes in this module. The enriched pathways were related to muscle. The critical genes were KLHL41, MYBPC2, and ERAP2. Single-gene GSEA identified the Hippo signaling pathway, basal cell carcinoma, cell adhesion molecules, and other pathways. Six miRNAs and 18 lncRNAs related to the critical genes constituted the ceRNA network and were verified using qPCR. The differential expression of KLHL41, MYBPC2, and ERAP2 at the protein level was verified using immunohistochemistry. KLHL41, MYBPC2, and ERAP2 genes are related to skin photoaging. The prediction model based on the three critical genes can indicate photoaging. These critical genes may have a role in skin photoaging by regulating cell growth, intercellular adhesion, and substance metabolism pathways., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Poly-L-lactide (PLLA) offers a unique possibility for processing into biocompatible, biodegradable, and implantable piezoelectric structures. With such properties, PLLA has potential to be used as an advanced tool for mimicking biophysical processes that naturally occur during the self-repair of wounds and damaged tissues, including electrostimulated regeneration. The piezoelectricity of PLLA strongly depends on the possibility of controlling its crystallinity and molecular orientation. Here, it is shown that modifying PLLA with a small amount (1 wt%) of crystalline filler particles with a high aspect ratio, which act as nucleating agents during drawing-induced crystallization, promotes the formation of highly crystalline and oriented PLLA structures. This increases their piezoelectricity, and the filler-modified PLLA films provide a 20-fold larger voltage output than nonmodified PLLA during ultrasound (US)-assisted activation. With 99% PLLA content, the ability of the films to produce reactive oxygen species (ROS) and increase the local temperature during interactions with US is shown to be very low. US-assisted piezostimulation of adherent cells directly attach to their surface (such as skin keratinocytes), stimulate cytoskeleton formation, and as a result cells elongate and orient themselves in a specific direction that align with the direction of PLLA film drawing and PLLA dipole orientation., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Background: Hepatitis C virus (HCV) infection remains a major public health problem in Chinese mainland. Investigation of the distribution of genotypes contributed to the prevention, diagnosis and treatment of HCV infection. Therefore, we conducted a study on the distribution of HCV genotypes and phylogenetic analysis to provide an up-to-date understanding of the molecular epidemiology of genotypes in Chinese mainland., Methods: Our retrospective multicenter study enrolled 11,008 samples collected between August 2018 and July 2019 from 29 provinces/municipalities (Beijing, Hebei, Inner Mongolia, Shanxi, Tianjin, Gansu, Ningxia, Shaanxi, Xinjiang, Heilongjiang, Jilin Liaoning, Henan, Hubei Hunan, Anhui, Fujian, Jiangsu, Jiangxi, Shandong, Shanghai Zhejiang, Guangdong, Guangxi, Hainan, Chongqing, Guizhou, Sichuan and Yunnan). Phylogenetic analysis of each subtype was performed to infer the evolutionary relationship of sequences from diverse regions. Two independent samples t tests were used for the comparison of continuous variables, and chi-square tests were used for the comparison of categorical variables., Results: Four genotypes (1, 2, 3 and 6) were found, including 14 subtypes. HCV genotype 1 was dominant, accounting for 49.2%, followed by genotypes 2, 3 and 6, accounting for 22.4%, 16.4%, and 11.9%, respectively. Additionally, the top five subtypes were 1b, 2a, 3b, 6a and 3a. Proportions of genotypes 1 and 2 decreased while genotypes 3 and 6 increased over past years (P < 0.001). Genotypes 3 and 6 were concentrated in the population aged 30 to 50 years, and male carriers had lower proportions of subtypes 1b and 2a than female carriers (P < 0.01). Genotypes 3 and 6 were more prevalent in southern parts of Chinese mainland. Nationwide spreads of subtypes 1b and 2a were associated with sequences from northern parts of Chinese mainland, while subtypes 3a, 3b and 6a were associated with sequences from southern parts of Chinese mainland., Conclusions: HCV subtypes 1b and 2a remained the most common subtypes in Chinese mainland, and their proportions decreased over the past years, while the proportions of genotypes 3 and 6 increased. Our investigation provided an accurate epidemiological picture of the circulating viral strains in Chinese mainland, contributing to the prevention, diagnosis and treatment of HCV infection., Trial Registration: Not applicable., (© 2023. The Author(s).)

Ferroptosis is involved in ischemia and reperfusion injury (IRI) of transplanted kidney. Understanding the molecular mechanisms of ferroptosis is essential to elucidate the pathogenesis of IRI. 1307 differentially expressed genes (DEGs) were obtained by GSE90861 retrieved from the GEO database. 29 ferroptosis-related DEGs were obtained from the intersection with FerrDb database, which were subjected to enrichment analysis and cytoHubba plugin for selecting the top three (IL6, ATF3 and JUN) as hub genes. Next, ROC analysis of hub genes showed good diagnostic prospects in both GSE90861 and GSE126805. Given the close link between ferroptosis and immunity, immunological analysis of CIBERSORTx revealed that the proportions of 10 cell types out of 22 immune cells in the transplanted kidney significantly changed after reperfusion. To study the relationship between IRI and ferroptosis, 15 male C57BL/6j mice were randomly divided into three groups: control (C), ischemia and reperfusion (IR), and IR + Fer-1 (IF) groups. The IRI mouse model not only developed significant histological damage changes, but also exhibited mitochondrial damage, iron accumulation, increased MDA, and decreased GSH. The ferroptosis inhibitor, Fer-1, ameliorated renal IRI, as demonstrated by rise of GPX4 and decline of TFRC, PTGS2 and ACSL4. In addition, hub genes were further confirmed by significant increase in IRI mouse model the same as the GEO database. In brief, ferroptosis-related hub genes (IL-6, ATF3 and JUN) screened were closely relevant to immune response and might be diagnostic biomarkers and therapeutic targets for IRI during renal transplantation, which could prevent renal allograft dysfunction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: Current echocardiography evaluation of right ventricular (RV) function, which heralds the prognosis in patients with systemic lupus erythematosus (SLE), is of limited utility. The non-invasive pressure-strain loop (PSL), an emerging technique, has been found to feasible, sensitive and accurate in the diagnosis of cardiovascular diseases. The aim of this study was to quantitatively evaluate, using the non-invasive PSL, the right ventricular myocardial work (RVMW) in SLE patients., Methods: Seventy-five SLE patients were recruited and grouped by pulmonary artery systolic pressure (PASP) into normal (group A, N = 26), mild (group B, N = 22) and moderate to severe (group C, N = 27) groups. Twenty-five healthy volunteers undergoing physical examination were recruited as the control group. Right ventricular global myocardial work index (RVGWI), global constructive work (RVGCW), global wasted work (RVGWW), global work efficiency (RVGWE), global longitudinal strain (RVGLS) and other conventional parameters were measured., Discussion: There were no differences between group A and the control group with respect to RVLS, RVGLS and all RVMW parameters (all p values > 0.05). RVGWI and RVGCW significantly differed among the other groups (all p values < 0.05). RVGWE was significantly lower and RVGWW was significantly higher in group C than in the control group and groups A and B (all p values < 0.05). Compared with the control group, RVGWW was significantly increased and RVGLS was significantly decreased in group B (all p values < 0.05). All but one RVMW parameter moderately to strongly correlated with SLE disease activity index (SLEDAI) and World Health Organization Functional Class (WHO-FC). RVGWW (area under the receiver operating characteristic curve [AUC] = 0.893) and RVGWE (AUC = 0.877) were sensitive parameters in detecting earlier cardiac dysfunction in SLE patients., Conclusion: RVGWW and RVGWE serve as sensitive and promising parameters in the integrative analysis of early right ventricular dysfunction in SLE patients. To conclude, non-invasive PSL, the novel method, facilitates the quantitative assessment of RVMW in SLE patients., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Septic acute kidney injury (AKI) is commonly associated with renal dysfunction and high mortality in patients. Owing to the rapid and violent occurrence of septic AKI with inflammation, there are no effective therapies to clinically treat it. Embelin, a natural product, has a potential regulatory role in immunocytes. However, the role and mechanism of embelin in septic AKI remains unknown. This study aimed to elucidate the role of embelin in macrophage regulation in lipopolysaccharide (LPS)-induced septic AKI. Embelin was intraperitoneally administered to mice after LPS injection. And bone marrow-derived macrophages (BMDMs) were subsequently isolated from the mice to explore the immunomodulatory role of embelin in macrophages. We found that embelin attenuated renal dysfunction and pathological renal damage in the LPS-induced sepsis mouse model. Molecular docking predicted that embelin could bind to phosphorylated NF-κB p65 at the ser536 site. Embelin inhibited the translocation of NF-κB p65 via phosphorylation at ser536 in LPS-induced AKI. It also reduced the secretion of IL-1β and IL-6 and increased the secretion of IL-10 and Arg-1 of BMDMs and mice after LPS stimulation, indicating that embelin suppressed macrophage M1 activation in LPS-induced AKI. Therefore, embelin attenuated LPS-induced septic AKI by suppressing NF-κB p65 at ser536 in activated macrophages. This study preclinically suggests a therapeutic role of embelin in septic AKI., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)

Objective: The influence of different Staphylococcus aureus variants on blood cells and coagulation system was evaluated by investigating the carrying status of drug resistance genes and virulence genes of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA)., Methods: A total of 105 blood culture-derived Staphylococcus aureus strains were collected. The carrying status of drug resistance genes mecA and three virulence genes tst , pvl, and sasX was analyzed by polymerase chain reaction (PCR). The changes in routine blood routine counts and coagulation indexes of patients infected with different strains were analyzed., Results: The results showed that the positive rate of mecA was consistent with that of MRSA. Virulence genes tst and sasX were detected only in MRSA. Compared with MSSA, patients infected with MRSA or MSSA patients infected with virulence factor, leukocyte count and neutrophil count in peripheral blood were significantly increased, and the platelet count decreased to a higher degree. Part thromboplastin time increased, D-dimer increased, but fibrinogen content decreased more. The changes of erythrocyte and hemoglobin had no significant correlation with whether Staphylococcus aureus carried virulence genes., Conclusion: The detection rate of MRSA in patients with positive Staphylococcus aureus in blood culture had exceeded 20%. The detected MRSA bacteria carried three virulence genes, tst , pvl, and sasX , which were more likely than MSSA. MRSA, which carries two virulence genes, is more likely to cause clotting disorders., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Jing Wei et al.)

We describe the opportunistic infections (OIs) of HIV/AIDS to understand the spectrum, mortality, and frequency of multiple coinfected OIs among HIV/AIDS patients in southern China, where OIs are severe. We carried out a retrospective cohort study of hospitalized HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from Jan. 2011 to May. 2019. The chi-square test was used to analyze cross-infection; the Kaplan‒Meier analysis was used to compare mortality. A total of 12,612 HIV-infected patients were admitted to this cohort study. Among them, 8982 (71.2%) developed one or more OIs. The overall in-hospital mortality rate was 9.0%. Among the patients, 35.6% coinfected one OI, and 64.4% coinfected more than two OIs simultaneously. Almost half of the patients (60.6%) had CD4 + T-cell counts < 200 cells/μL. Pneumonia (39.8%), tuberculosis (35.3%), and candidiasis (28.8%) were the most common OIs. Coinfected cryptococcal meningitis and dermatitis are the most common combined OIs. The rate of anaemia (17.0%) was highest among those common HIV-associated complications. Multiple OIs are commonly found in hospitalized HIV/AIDS patients in southwestern China, which highlights the need for improved diagnosis and treatment., (© 2022. The Author(s).)

Background: Pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) play significant roles in predicting discontinuing treatment outcomes. However, their role in pregnancy has rarely been reported. We aimed to evaluate the performance of pgRNA and HBcrAg kinetics in predicting HBeAg seroconversion and HBsAg reduction postpartum in HBeAg-positive pregnant women., Methods: Pregnant HBeAg-positive patients receiving antiviral prophylaxis and ceasing treatment postpartum were included. PgRNA and HBcrAg levels were measured before treatment, at 32 weeks of gestation, and at treatment withdrawal postpartum. Other virological and biochemical parameters were regularly examined until 96 weeks postpartum., Results: Of 76 pregnant chronic hepatitis B (CHB) carriers with a median treatment duration of 18.1 weeks, HBeAg seroconversion and HBsAg reduction >0.3 log 10 IU/mL at 96 weeks postpartum occurred in 8 (10.5%) and 13 (17.1%) patients, respectively. HBsAg correlated most strongly with pgRNA, while HBeAg correlated most strongly with HBcrAg. Multivariable regression analysis revealed that postpartum pgRNA decline and peak ALT levels were independent predictors of HBsAg reduction. The area under the curve of the regression model was 0.79 and reached as high as 0.76 through bootstrapping validation. The calibration plot showed that the nomogram had a performance similar to that of the ideal model. A decision tree was established to facilitate application of the nomogram. In addition, HBcrAg kinetics, as an independent predictor, performed poorly in predicting HBeAg seroconversion., Conclusions: Postpartum pgRNA decline together with peak ALT levels may identify patients with a higher probability of HBsAg reduction after treatment cessation postpartum among pregnant CHB carriers receiving antiviral prophylaxis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Liu, Li, Zhang, Zhong, Tang, Chang, Wang, Duan and Hu.)

Background: Ischemia and reperfusion injury (IRI) is an ineluctable immune-related pathophysiological process during organ transplantation, which not only causes a shortage of donor organs, but also has long-term and short-term negative consequences on patients. Severe IRI-induced cell death leads to the release of endogenous substances, which bind specifically to receptors on immune cells to initiate an immune response. Although innate and adaptive immunity have been discovered to play essential roles in IRI in the context of organ transplantation, the pathway and precise involvement of the immune response at various stages has not yet to be elucidated., Methods: We combined "IRI" and "organ transplantation" with keywords, respectively such as immune cells, danger signal molecules, macrophages, neutrophils, natural killer cells, complement cascade, T cells or B cells in PubMed and the Web of Science to search for relevant literatures., Conclusion: Comprehension of the immune mechanisms involved in organ transplantation is promising for the treatment of IRI, this review summarizes the similarities and differences in both innate and adaptive immunity and advancements in the immune response associated with IRI during diverse organ transplantation., (© 2022. The Author(s).)

Dimeric boronic acids kill Mycobacterium tuberculosis ( Mtb ) by targeting mycobacterial specific extracellular glycans, removing the requirement for a therapeutic agent to permeate the complex cell envelope. Here we report the successful development and use of new 'clickable' boronic acid probes as a powerful method to enable the direct detection and visualisation of this unique class of cell-surface targeting antitubercular agents.

Accurate prediction of the extent of fibrosis is of great clinical importance in patients infected with chronic hepatitis B (CHB). This study aimed to compare the performance of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in evaluating liver fibrosis stages and to identify optimized cutoffs to exclude cirrhosis. Consecutive patients with CHB with liver biopsies were enrolled and randomly divided into derivation and validation cohorts. Areas under the receiver operating characteristic curve were used to evaluate the diagnostic performance of APRI, FIB-4, and GPR to distinguish fibrosis stages. New cutoffs with a sensitivity of at least 90% and a negative predictive value (NPV) of more than 95% were identified. A total of 880 individuals were enrolled in this study. The derivation data set consisted of 617 patients, with 82 patients with cirrhosis. In the validation cohort (n = 263), 29 patients had cirrhosis. APRI, FIB-4, and GPR had comparable diagnostic performance for diagnosing significant fibrosis. GPR outperformed APRI (p < 0.05) in the prediction of cirrhosis. A newly identified GPR score of 0.35 had a sensitivity and NPV of 93.9% and 98.0%, respectively, and misclassified 5 of 82 (6.1%) patients with cirrhosis in the derivation group. All new cutoffs identified in this study also reached our goal in the validation cohort. The new GPR score could rule out a larger proportion of individuals without cirrhosis, and the subgroup analysis showed more stable performance. However, the lower cutoff dose increases the need for further testing compared to the conventional cutoff. Conclusion: A newly identified cutoff for GPR (<0.35) could rule out more patients without cirrhosis compared to APRI and FIB-4 and have low misclassification rates., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Patients infected with hepatitis C (HCV) genotype (GT) 3, especially GT3b, are still difficult to cure. GT3b is more common than GT3a in southwestern China. Here we aimed to investigate the prevalence of naturally occurring RASs in HCV GT3 in southwestern China and performed phylogenetic analysis., Methods: Serum samples were collected from patients with HCV GT3 infection. Sanger sequencing was used to validate resistance-associated substitutions (RASs). Phylogenetic analysis was performed using MEGA X and the observed-minus-expected-squared algorithm was used to analyze amino acid covariance., Results: A total of 136 patients were enrolled, including 41 HCV GT3a and 95 GT3b infected patients. In the NS5A region, the proportion of RASs found in GT3b (99%) was notably higher than in GT3a (9%). In the NS3 region, RASs prevalence in GT3b (5%) was lower than in GT3a (24%). NS5B-specific RASs were rare. Both the NS5A30k and L31 M substitutions occurred in 96% of GT3b sequences. The A30K + L31M combination was found in 94% of GT3b isolates, however, there were no A30K or L31M mutations observed in the GT3a sequence., Conclusions: Significant differences were observed between HCV GT3a and GT3b in terms of RAS prevalence. The origin of GT3a appears to be more diverse compared with GT3b in southern China. Studies specifically aimed at HCV GT3b infection should be initiated to gain more insight into this subtype., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Strict quarantines can prevent the spread of the COVID-19 pandemic, but also increase the risk of mental illness. This study examined whether the people who have experienced repeated home quarantine performance more negative emotions such as anxiety, depression, and post-traumatic stress disorder (PTSD) in a Chinese population., Methods: We collected data from 2,514 participants in Pi County, Chengdu City, and stratified them into two groups. Group 1 comprised 1,214 individuals who were quarantined only once in early 2020, while Group 2 comprised 1,300 individuals who were quarantined in early 2020 and again in late 2020. Both groups were from the same community. The GAD-7, PHQ-9, and PCL-C scales were used to assess symptoms of anxiety, depression, and PTSD between the two groups., Results: Analyses showed that total PHQ-9 scores were significantly higher in Group 2 than in Group 1 ( p < 0.001) and the quarantine times and age are independent predictors of symptoms of depression ( p < 0.001). The two groups did not differ significantly in total GAD-7 or PCL-C scores., Conclusion: Increasing quarantine times was associated with moderate to severe depression symptoms, but not with an increase in symptoms of anxiety or PTSD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Wang, Li, Luo, Hao and Xu.)

Introduction: The cognitive dysfunction associated with nitrous oxide abuse is gradually becoming a major global public health concern. Despite the increasing prevalence of nitrous oxide abuse, there are currently no authorised/approved treatment options. Hyperbaric oxygen therapy (HBOT) has been proven to be an efficient method to improve cognitive function. The current randomised, double-blinded, placebo-controlled trial will explore the effect of HBOT on cognitive dysfunction induced by nitrous oxide abuse., Methods and Analysis: Eighty participants who abuse nitrous oxide and have cognitive dysfunction, including memory decline, disorientation, attention deficits, slower reactions and learning disabilities, will be included in the trial. They will be randomly assigned to receive either HBOT or sham-HBOT 90-120 min once daily for 5 days per week for 2 weeks. The primary outcome will be the improvement in the total score of the MATRICS Consensus Cognitive Battery, which will measure comprehensive cognitive function between the two groups. Additionally, attention will be measured by integrated visual and auditory continuous performance tests, executive function will be measured by the Wisconsin card sorting test, intelligence will be measured by Raven's standard progressive matrices and cognitive control will be measured by the Stroop colour word interference test., Ethics and Dissemination: This protocol was approved by the West China Hospital of Sichuan University Biomedical Research Ethics Committee. The report of the study will be disseminated via scientific forums including peer-reviewed publications and presentations at national and international conferences., Trial Registration Number: Chinese Clinical Trial Registry (ChiCTR2100047111)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The biological functions of exosomes and microRNAs (miRs) in nasopharyngeal carcinoma (NPC) remain largely unexplored. Here, miR-197-3p was screened and identified, and whose level was reduced in serum and exosomes of patients with NPC. MiR-197-3p might be a good diagnostic and prognostic indicator. Our data showed that miR-197-3p expression was closely related to radioresistance, apoptosis, proliferation, migration, and survival of NPC. Inhibition of miR-197-3p expression in vitro could promote the proliferation and migration of NPC cells, while promotion of miR-197-3p expression in vivo could significantly inhibit the growth and enhance the radiosensitivity of NPC cells. From the perspective of mechanism, miR-197-3p could inhibit AKT/mTOR phosphorylation activation, inhibit an activated pathway of AKT/mTOR, target Heat Shock 70-kDa Protein 5(HSPA5) related to endoplasmic reticulum homeostasis, inhibit HSPA5-mediated autophagy, and reverse the radioresistance of NPC. Interestingly, exosomal miR-197-3p (EXO-miR-197-3p) reduced the proliferation and migration potential of NPC cells in vitro , and tumor growth and radioresistance of NPC cells in vivo . EXO-miR-197-3p inhibited NPC progression and radioresistance by regulating AKT/mTOR phosphorylation activation and HSPA5-mediated autophagy. In conclusion, our results highlight the potential of EXO-miR-197-3p as an effective radiosensitizer and therapeutic agent for refractory NPC., (© The author(s).)

Background: Coronavirus disease 2019 (COVID-19) can result in an endothelial dysfunction in acute phase. However, information on the late vascular consequences of COVID-19 is limited., Methods: Brachial artery flow-mediated dilation (FMD) examination were performed, and inflammatory biomarkers were assessed in 86 survivors of COVID-19 for 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients., Results: Brachial artery FMD was significantly lower in the survivors of COVID-19 than in the healthy controls and risk factor-matched controls [median (IQR) 7.7 (5.1-10.7)% for healthy controls, 6.9 (5.5-9.4)% for risk factor-matched controls, and 3.5(2.2-4.6)% for COVID-19, respectively, p < 0.001]. The FMD was lower in 25 patients with elevated tumor necrosis factor (TNF)-α [2.7(1.2-3.9)] than in 61 patients without elevated TNF-α [3.8(2.6-5.3), p = 0.012]. Furthermore, FMD was inversely correlated with serum concentration of TNF-α (r = -0.237, p = 0.007)., Conclusion: Survivors of COVID-19 have a reduced brachial artery FMD, which is inversely correlated with increased serum concentration of TNF-α. Prospective studies on the association of endothelial dysfunction with long-term cardiovascular outcomes, especially the early onset of atherosclerosis, are warranted in survivors of COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Zhou, Huang, Liu, Bi, Zhu, Sun, Tang, Li, Zhang, Zhu, Cheng, Liu and Deng.)

The HIV/AIDS prevalence in female sex workers (FSWs) and elderly male clients is increasing in Guangxi, China, but the transmission relationship between them remains unclear. This study aims to illuminate the transmission network between FSWs and elderly male clients using molecular epidemiological analyses. Phylogenetic analysis indicated that CRF01&#95;AE was the dominant strain, followed by CRF07&#95;BC and CRF08&#95;BC in both groups. Multivariate logistic regression analysis indicated that viral loads of 50 to 1000 copies/mL, immunological treatment failure and CRF07&#95;BC were risk factors for entering the transmission network. Transmission network analysis showed that CRF07&#95;BC tended to form large clusters, whereas CRF01&#95;AE tended to form multiple but small clusters. Two groups of 11 FSWs and 169 clients were intricately intertwined. Spatial analysis demonstrated the formation of hotspots and clusters of transmission sharing regional differences. In conclusion, our study provides direct genetic evidence of transmission linkages between FSWs and elderly male clients. Although the CRF01&#95;AE subtype was still the predominant subtype in the region, the higher degree and larger clusters found in CRF07&#95;BC illustrate a rapid and intensive uptrend, which is expected to increase its prevalence in the region in the future.

Background: Coronavirus disease 2019 can result in myocardial injury in the acute phase. However, information on the late cardiac consequences of coronavirus disease 2019 (COVID-19) is limited. Methods: We conducted a prospective observational cohort study to investigate the late cardiac consequences of COVID-19. Standard echocardiography and myocardial strain assessment were performed, and cardiac blood biomarkers were tested in 86 COVID-19 survivors 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. Results: There were no significant differences in all echocardiographic structural and functional parameters, including left ventricular (LV) global longitudinal strain, right ventricular (RV) longitudinal strain, LV end-diastolic volume, RV dimension, and the ratio of peak early velocity in mitral inflow to peak early diastolic velocity in the septal mitral annulus (E/e') among COVID-19 survivors, healthy controls and risk factor-matched controls. Even 26 patients with myocardial injury at admission did not have any echocardiographic structural and functional abnormalities. There were no significant differences among the three groups with respect to serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI). Conclusion: This study showed that COVID-19 survivors, including those with myocardial injury at admission and those with severe and critical types of illness, do not have any echocardiographic evidence of cardiac structural and functional abnormalities 327 days after diagnosis., 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 © 2021 Gao, Zhou, Huang, Liu, Bi, Zhu, Sun, Tang, Li, Zhang, Sun, Cheng, Liu and Deng.)

During embryonic heart development, the progenitor cells in the epicardium would migrate and differentiate into noncardiomyocytes in myocardium and affect the integrity of ventricular wall, but the underlying mechanism has not been well studied. We have found that myocardium geranylgeranyl diphosphate synthase (Ggpps), a metabolic enzyme for cholesterol biosynthesis, is critical for cardiac cytoarchitecture remodelling during heart development. Here, we further reveal that epicardial Ggpps could also regulate ventricular wall architecture integrity. Epicardium-specific deletion of Ggpps before embryonic day 10.5 (E10.5) is embryonic lethal, whereas after E13.5 is survival but with defects in the epicardium and ventricular wall structure. Ggpps deficiency in the epicardium enhances the proliferation of epicardial cells and disrupts cell‒cell contact, which makes epicardial cells easier to invade into ventricular wall. Thus, the fibroblast proliferation and coronary formation in myocardium were found enhanced that might disturb the coronary vasculature remodelling and ventricular wall integrity. These processes might be associated with the activation of YAP signalling, whose nuclear distribution is blocked by Ggpps deletion. In conclusion, our findings reveal a potential link between the cholesterol metabolism and heart epicardium and myocardium development in mammals, which might provide a new view of the cause for congenital heart diseases and potential therapeutic target in pathological cardiac conditions., (© The Author(s) (2021). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

The Mott state in 1T-TaS 2 is predicted to host quantum spin liquids (QSLs). However, its insulating mechanism is controversial due to complications from interlayer coupling. Here, we study the charge transfer state in monolayer 1T-NbSe 2 , an electronic analogue to TaS 2 exempt from interlayer coupling, using spectroscopic imaging scanning tunneling microscopy and first-principles calculations. Monolayer NbSe 2 surprisingly displays two types of star of David (SD) motifs with different charge transfer gap sizes, which are interconvertible via temperature variation. In addition, bilayer 1T-NbSe 2 shows a Mott collapse by interlayer coupling. Our calculation unveils that the two types of SDs possess distinct structural distortions, altering the effective Coulomb energies of the central Nb orbital. Our calculation suggests that the charge transfer gap, the same parameter for determining the QSL regime, is tunable with strain. This finding offers a general strategy for manipulating the charge transfer state in related systems, which may be tuned into the potential QSL regime.

Background: Bladder cancer (BLCA) is one of the most common urinary malignancies with poor prognosis. There is an unmet need to develop novel robust tools to predict prognosis and treatment efficacy for BLCA., Methods: The hypoxia-related genes were collected from the Molecular Signatures Database. The TCGA-BLCA cohort was downloaded from the Cancer Genome Atlas and then was randomly divided into training and internal validation sets. Two external validation cohorts were gathered from Gene Expression Omnibus. Also, another independent validation cohort (Xiangya cohort) was collected from our hospital. The Cox regression model with the LASSO algorithm was applied to develop the hypoxia risk score. Then, we correlated the hypoxia risk score with the clinical outcomes, the tumor microenvironment (TME) immune characteristics, and the efficacy prediction for several treatments, which included cancer immunotherapy, chemotherapy, radiotherapy, and targeted therapies., Results: Hypoxia risk score was an independent prognostic factor. A high-risk score indicated an inflamed TME based on the evidence that hypoxia risk score positively correlated with the activities of several cancer immunity cycles and the infiltration levels of many tumor-infiltrating immune cells, such as CD8 + T cells, Dendritic cells, and NK cells. Consistently, the hypoxia risk score was positively related to the expression of several immune checkpoints, such as PD-L1, PD-1, CTLA-4, and LAG-3, as well as the T cell inflamed score. Furthermore, the hypoxia risk score positively correlated with the enrichment scores of most immunotherapy-positive gene signatures. Therefore, patients with higher risk score may be more sensitive to cancer immunotherapy. Meanwhile, the hypoxia risk score was positively related to the sensitivities of several chemotherapeutic drugs, including Cisplatin, Docetaxel, Paclitaxel, Bleomycin, Camptothecin, and Vinblastine. Similarly, the enrichment scores for radiotherapy-predicted pathways and EGFR ligands were higher in the high-risk score group. Conversely, the enrichment scores of several immunosuppressive oncogenic pathways were significantly higher in the low-risk score group, such as the WNT-β-catenin network, PPARG network, and FGFR3 network., Conclusions: We developed and validated a new hypoxia risk score, which could predict the clinical outcomes and the TME immune characteristics of BLCA. In general, the hypoxia risk score may aid in the precision medicine for BLCA., 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 © 2021 Liu, Tang, Qi, Othmane, Yang, Chen, Hu and Zu.)

Background: Previous studies have shown that sofosbuvir-based regimens yield high sustained virological response rates in patients with hepatitis C virus (HCV) infection except for genotype 3b complicated with cirrhosis. This real-world study aims to explore the efficacy and safety of sofosbuvir-based regimens in Chinese patients with genotypes 3 and 6 infections, especially the impact of ribavirin coadministration on sustained virological response in cirrhotic patients with genotype 3b infection., Methods: This is a retrospective cohort study that included 101 patients initiated on sofosbuvir-based regimens. The main endpoint of treatment was sustained virological response at posttreatment week 12 (SVR12)., Results: Overall, the SVR12 rates were 95.0% (96/101); specifically, the rates were 100% in sofosbuvir, 88.2% in sofosbuvir+ribavirin, 100% in sofosbuvir+daclatasvir, 100% in sofosbuvir+daclatasvir+ribavirin, 95.0% in sofosbuvir/velpatasvir, and 97.1% in sofosbuvir/velpatasvir+ribavirin (p=0.534). The SVR12 rates were comparable in patients infected with genotypes 3 and 6 (93.2% versus 97.6%, p=0.339). The SVR12 rate was 93.9% in cirrhotic patients (31/33). Among those infected with genotype 3, the SVR12 rate was 91.7% (22/24); the rate was 95.0% in those with ribavirin coadministration regimens, which was numerically higher than the 75.0% in those without ribavirin. However, no statistical difference was found (p=0.312). In total, five patients failed to achieve SVR12, including 3 patients with genotype 3b infection treated with ribavirin coadministration regimens (one of them was cirrhotic), 1 cirrhotic patient with genotype 3k infection, and 1 noncirrhotic patient with genotype 6a infection. No severe adverse event occurred., Conclusion: Real-world data show that sofosbuvir-based regimens are highly effective and safe for patients with HCV genotypes 3 and 6 infections., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Tang et al.)

Exploring two-dimensional (2D) van der Waals (vdW) systems is at the forefront of materials of physics. Here, through molecular beam epitaxy on graphene-covered SiC(0001), we report successful growth of AlSb in the double-layer honeycomb (DLHC) structure, a 2D vdW material which has no direct analogue to its 3D bulk and is predicted to be kinetically stable when freestanding. The structural morphology and electronic structure of the experimental 2D AlSb are characterized with spectroscopic imaging scanning tunneling microscopy and cross-sectional imaging scanning transmission electron microscopy, which compare well to the proposed DLHC structure. The 2D AlSb exhibits a band gap of 0.93 eV versus the predicted 1.06 eV, which is substantially smaller than the 1.6 eV of bulk. We also attempt the less-stable InSb DLHC structure; however, it grows into bulk islands instead. The successful growth of a DLHC material here demonstrates the feasibility for the realization of a large family of 2D DLHC traditional semiconductors with characteristic excitonic, topological, and electronic properties.

Introduction: Traditional Chinese medicine (TCM) has been fully committed to the treatment of coronavirus disease 2019 (COVID-19) in China. An increasing number of clinical trials have been registered to evaluate the effects of TCM for COVID-19. The aim of this study was to review the existing TCM clinical trial registrations and identify potentially promising and available TCM therapies, in order to provide a reference for the global management of COVID-19., Methods: All clinical trials on TCM for COVID-19 registered in registry platforms worldwide were searched. The data of registration temporal trend, design, objective, interventions, and relevant information were reviewed and summarized., Results: 161 TCM trials were identified from three registries (January 26 to May 14 2020,). Of these, 94 (58.4%) were randomized controlled trials and 114 trials (70.8%) assessed therapeutic effects; while the remainder focused on prevention, rehabilitation, and the epidemiology of TCM syndromes. Eight trials (5.0%) had completed their recruitment. TCM interventions with potential for further evaluation in terms of prevention were moxibustion, Huoxiang Zhengqi pill and Jinye Baidu granules. For treatment of COVID-19, Qingfei Paidu decoction, Huashi Baidu decoction, Lianhua Qingwen capsules, Toujie Quwen granules and Xiyanping injection, and Xuebijing injection were to be tested for their therapeutic effects and symptoms relief. For rehabilitation, Tai Chi and Liuzijue were to be tested for improving patients' lung function., Conclusion: Some potentially promising TCM interventions have been identified and deserve further evaluation to establish their evidence base, particularly on populations outside of China., (© 2020 Elsevier GmbH. All rights reserved.)

Stem cell transplantation has been applied to treat spinal cord injury (SCI) in clinical trials for many years. However, the clinical efficacies of stem cell transplantation in SCI have been quite diverse. The purpose of our study was to systematically investigate the efficacy of stem cell transplantation in patients with SCI. The PubMed, Web of Science, Ovid-Medline, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang, and SinoMed databases were searched until October 27, 2020. Quantitative and qualitative data were analyzed by Review Manager 5.3 and R. Nine studies ( n = 328) were included, and the overall risk of bias was moderate. The ASIA Impairment Scale (AIS) grading improvement rate was analyzed in favor of stem cell transplantation group [odds ratio (OR) = 6.06, 95% confidence interval (CI): 3.16-11.62, P < 0.00001]. Urodynamic indices also showed improvement in bladder function. In subgroup analyses, the results indicated that in patients with complete (AIS A) SCI, with the application of cell numbers between n *(10 7 -10 8 ), two cell types (i.e., bone marrow-derived mesenchymal stem cells and bone marrow mononuclears), and treatment time of more than 6 months, stem cell transplantation was more beneficial for sensorimotor function ( P < 0.05 for all groups). The risk of fever incidence in the stem cell transplantation group was 4.22 (95% CI: 1.7-10.22, P = 0.001), and principal component analysis (PCA) suggested it was more related to transplanted cell numbers. Thus, stem cell transplantation can promote functional recovery in SCI patients. Moreover, the type and quantity of transplanted stem cells and treatment time are important factors affecting the therapeutic effect of stem cell transplantation in SCI. Further studies are needed to evaluate the effects and elucidate the mechanisms of these factors on stem cell therapy in SCI.

Electrochemical sensing performance is often compromised by electrode biofouling (e.g., proteins nonspecific binding) in complex biological fluids; however, the design and construction of a robust biointerface remains a great challenge. Herein, inspired by nature, we demonstrate a robust polydopamine-engineered biointerfacing, to tailing zwitterionic molecules (i.e., sulfobetaine methacrylate, SBMA) through Michael Addition. The SBMA-PDA biointerface can resist proteins nonspecific binding in complex biological fluids while enhancing interfacial electron transfer and electrochemical stability of the electrode. In addition, this sensing interface can be integrated with tissue-implantable electrode for in vivo analysis with improved sensing performance, preserving ca. 92.0% of the initial sensitivity after 2 h of implantation in brain tissue, showing low acute neuroinflammatory responses and good stability both in normal and in Parkinson's disease (PD) rat brain tissue., (© 2020 Wiley-VCH GmbH.)

Purpose: Previously, we have demonstrated the use of lipidoid (lipid-like) nanoparticles (e.g., "1-O16B") for gene delivery to live cells, as an alternative to viral vectors. Here, we encapsulate VEGF siRNA (siVEGF) in bioreducible lipidoid nanoparticles and examine whether these nanocomplexes can reduce intravitreal neovascularization in a rodent model of oxygen-induced retinopathy (OIR)., Methods: Firstly, we constructed siVEGF-nanoparticles (NPs) and transfected human umbilical vein endothelial cells, which caused significantly reduced expression of VEGF, compared to exposure to siVEGF in solution. Secondly, we compared the effect of intravitreal siVEGF-NPs and an anti-VEGF drug (ranibizumab) on retinal vascular development and VEGF mRNA/protein expression in the retinas of a rat model of OIR., Results: Compared to a non-functional lipid vehicle control group, the level of VEGF mRNA and protein was significantly lower in the siVEGF-NP group (p < 0.01), but the level of VEGF mRNA was not significantly lower in the ranibizumab group. Anatomically, the number of retinal neovascular endothelial nuclei that had protruded through the internal limiting membrane and the number of areas of non-perfusion of the retina were both significantly lower in the siVEGF-NP group and the ranibizumab group than in the OIR group (p < 0.01)., Conclusion: Our results demonstrate that bioreducible lipidoid nanoparticles conveying VEGF siRNA can effectively inhibit retinal neovascularization in a rodent model of OIR, and reduce the expression of VEGF mRNA and protein. This novel treatment modality could have profound implications for treating retinal angiogenic diseases.

The abundance of bacterial effectors have inspired us to explore their potential in rewiring malignant cell signaling. Their incapability for entering cells, however, hinders such application. Herein we developed a cationic lipid-based high throughput library screening platform for effective intracellular delivery of bacterial effectors. As the misregulated MAPK signaling is a hallmark of many types of cancer, we turned to the Shigella effector OspF which irreversibly inactivates ERK, the terminal component of MAPK cascade. We created a function-based screening assay to obtain AMPA-O16B lipid nanoparticles for effective OspF intracellular delivery, which inhibited the malignant MAPK signaling and tumor growth in vitro and in vivo. Furthermore, the optimized lipid nanoparticle formulation can deliver OspF to modulate the immunosuppressive responses in macrophages. Our work is a general strategy to explore the therapeutic potentials of naturally evolved bacterial effectors., (© 2020 Wiley-VCH GmbH.)