Search

Abstract In a molecule formed by two atoms, energy difference between bonding and antibonding orbitals depends on distance between the two atoms. However, exploring molecular orbitals of two natural atoms with tunable distance has remained an outstanding experimental challenge. Graphene quantum dots can be viewed as relativistic artificial atoms, thus offering a unique platform to study molecular physics. Here, through scanning tunneling microscope, we create and directly visualize the formation process of relativistic artificial molecules based on two coupled graphene quantum dots with tunable distance. Our study indicates that energy difference between the bonding and antibonding orbitals of the lowest quasibound state increases linearly with inverse distance between the two graphene quantum dots due to the relativistic nature of the artificial molecule. For quasibound states with higher orbital momenta, the coupling between these states leads to half-energy spacing of the confined states because the length of the molecular-like orbit is approximately twice that of the atomic-like orbit. Evolution from ring-like whispering-gallery modes in the artificial atoms to figure-eight orbitals in the artificial molecules is directly imaged. The ability to resolve the coupling and orbitals of the relativistic artificial molecule at the nanoscale level yields insights into the behavior of quantum-relativistic matter.

Abstract Background This study aims to explore the relationship between female reproductive factors (age at first birth (AFB), age at last birth (ALB), gravidity, and number of live birth (NLB)) and prevalence of depression among the US women. Methods The relationship between AFB, ALB, gravidity, and NLB with the prevalence of depression was explored using publicly available data from the National Health and Nutrition Examination Survey 2005–2018. This cross-sectional study included female participants aged 20 years and older, with reproductive factors and depressive symptoms reported by the participants. Depression was evaluated using the Patient Health Questionnaire-9, with a score of ≥ 10 representing major depression disorder. Weighted multivariable logistic regression and restricted cubic splines (RCS) were utilized to explore the association of AFB, ALB, gravidity and NLB with depression. Results In this study of 11,488 US women, 1,332 (11.6%) women had depression. Compared to the reference group of women with AFB under 18 years, the fully adjusted ORs and 95% CIs for depression were 0.83 (95% CI: 0.68–0.99), 0.75 (95% CI: 0.60–0.95), and 0.69 (95% CI: 0.51–0.93) for women with AFB of 21–23, 24–26, and 27–29 years, respectively. Furthermore, women with five or more pregnancies had a significantly higher prevalence of depression compared to those with two or fewer pregnancies (OR = 1.20, 95% CI: 1.01–1.42). RCS models demonstrated linear associations of ALB, gravidity and NLB with the prevalence of depression. Additionally, the RCS analysis revealed a roughly L-shaped relationship between AFB and prevalence of depression. Conclusions Women with later AFB are associated with a decreased prevalence of depression, while multiple pregnancies are associated with an increased prevalence of depression. These findings suggest that reproductive factors should be considered when screening for and developing preventive strategies for depression.

Abstract Moiré structures formed by twisting three layers of graphene with two independent twist angles present an ideal platform for studying correlated quantum phenomena, as an infinite set of angle pairs is predicted to exhibit flat bands. Moreover, the two mutually incommensurate moiré patterns among the twisted trilayer graphene (TTG) can form highly tunable moiré quasicrystals. This enables us to extend correlated physics in periodic moiré crystals to quasiperiodic systems. However, direct local characterization of the structure of the moiré quasicrystals and of the resulting flat bands are still lacking, which is crucial to fundamental understanding and control of the correlated moiré physics. Here, we demonstrate the existence of flat bands in a series of TTGs with various twist angle pairs and show that the TTGs with different magic angle pairs are strikingly dissimilar in their atomic and electronic structures. The lattice relaxation and the interference between moiré patterns are highly dependent on the twist angles. Our direct spatial mappings, supported by theoretical calculations, reveal that the localization of the flat bands exhibits distinct symmetries in different regions of the moiré quasicrystals.

Sinonovacula constricta is one of the four traditional cultured shellfish in China. The salinity in the aquaculture water body is easily affected by tides, seasonal rainfall, and high temperatures, and often fluctuates to different degrees. This affects the physiological activities of S. constricta and causes a series of changes in the structure of the osmoregulation organs, osmotic pressure, ion transport, and free amino acid (FAA) content in the body to adapt to the changes in environmental salinity. Aquatic animals can regulate cell volume and maintain osmotic pressure balance through FAAs. This mechanism has been proven in aquatic animals, such as Meretrix lusoria, Crassostrea gigas, Haliotis discus hannai, Penaeus vannamei, and Portunus trituberculatus. The common FAAs that regulate osmotic pressure in bivalves mainly include Ala, Gly, Pro, and Tau. Whether FAAs play an osmoregulation role in S. constricta, whether their involvement in osmoregulation is similar to that in other shellfish, and what the metabolic pathway is of main FAAs deserve further study. This study explored the changes of osmotic pressure and FAAs in the gill, foot, and hemolymph of S. constricta after salinity stress and analyzed the sequence characteristics, tissue expression, and mRNA expression characteristics after salinity stress and RNA interference (RNAi) of the Sc-CARNS gene, and the changes of alanine and carnosine contents. The osmotic pressure and FAA contents in the gills, foot, and hemolymph of S. constricta under different salinities (5, 20, and 35) were measured by freezing point osmometer and automatic amino acid analyzer. At the same time, the expression of the Sc-CARNS gene in the foot under different salinities (5, 20, and 35) was analyzed by RT-qPCR and RNAi technology. The content of alanine was determined with the shellfish alanine ELISA kit. The content of carnosine was determined by phthalaldehyde colorimetry. The results showed that the osmotic pressure in the gills, foot, and hemolymph of S. constricta significantly decreased within 1–72 h under low salt stress (P < 0.05), while under high salt stress, the osmotic pressure in the gills, foot, and hemolymph reached a steady state within 24 h, which was consistent with the osmotic pressure of external seawater. Compared with the control group, the osmotic pressure in the gills, foot, and hemolymph decreased by 66.7%, 69.7%, and 71.6%, respectively, when the salinity was low. The wet weight of tissues was then increased by 68.3%, 67.5%, and 70.2%, respectively. At the same stress time, the osmotic pressure of each group of S. constricta was salinity 35 > salinity 20 > salinity 5. Under normal salinity, the FAAs with the highest content in the gills, foot, and hemolymph of S. constricta were Gly, Arg, and Gly, respectively. After salinity stress, the content of total free amino acids in all tissues increased significantly with the increase of salinity. The main FAAs with the largest content change in the gills, foot, and hemolymph, respectively, were Ala, Gly, Glu, and Pro; Ala, Gly, Arg, and Tua; and Ala, Ser, Thr, and Gly. Ala was the most variable FAA in all tissues. According to the transcriptome results of S. constricta after salinity stress, it was speculated that Sc-CARNS is related to osmotic regulation. The expression of Sc-CARNS was the highest in the muscle type tissues of S. constricta, followed by the gills, and was the lowest in the hepatopancreas. After low salt stress, the expression of the Sc-CARNS gene mRNA in S. constricta increased at first and then decreased with the stress time, and was significantly higher than that in the control group after 4 h of stress (P < 0.01), and reached the peak at 24 h. The content of alanine decreased significantly with time, and the content of carnosine increased significantly with time (P < 0.05). After high salt stress, the expression of Sc-CARNS decreased, and there was no significant change compared with the control group. The content of alanine first increased, then decreased, and then increased after 8 h, and was not lower than that of the control group. The content of carnosine showed a decreasing trend after 24 h. After RNAi, the expression level of Sc-CARNS mRNA in the interference group decreased first and then increased with the interference time under normal salinity. At 24 and 48 h, the expression level of Sc-CARNS mRNA was significantly lower than that of negative control (P < 0.05), and the interference efficiency was 24% and 69%, respectively. The interference efficiency at 48 h was the highest. In the interference group, the content of alanine first increased and then decreased, and the content of carnosine first decreased and then increased, reaching the maximum at 48 h. Under low salt stress, the expression of Sc-CARNS mRNA increased, the content of alanine decreased, and the content of carnosine increased after interference for 0–24 h. After interference for 24 h and 96 h, the mRNA expression of Sc-CARNS and the contents of alanine and carnosine did not change significantly in control group and diethyl pyrocarbonate treated water. The expression level of Sc-CARNS mRNA in the interference group first decreased and then increased with the interference time, the content of alanine first increased and then decreased with time, and the content of carnosine first decreased and then increased. At 48 h, the expression of Sc-CARNS mRNA and the content of carnosine were significantly decreased, and the content of alanine was significantly increased. The results showed that S. constricta has a variable osmotic pressure. Ala as a FAA in vivo contributed the most to osmotic regulation. Moreover, carnosine synthetase was the key enzyme for converting alanine to carnosine. This study revealed the key mechanism of osmotic pressure regulation under low salt stress and provided a basis for revealing the unique salinity tolerance mechanism of Solenida shellfish.

Abstract Taxol serves as an efficient natural anticancer agent with extensive applications in the treatment of diverse malignancies. Although advances in synthetic biology have enabled the de novo synthesis of taxol precursors in various microbial chassis, the total biosynthesis of taxol remains challengable owing to the restricted oxidation efficiency in heterotrophic microbes. Here, we engineered Synechocystis sp. PCC 6803 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and taxol biosynthetic enzymes for production of taxadiene-5α-ol (T5α-ol), the key oxygenated intermediate of taxol. The best strain DIGT-P560 produced up to 17.43 mg/L of oxygenated taxanes and 4.32 mg/L of T5α-ol. Moreover, transcriptomic analysis of DIGT-P560 revealed that establishing a oxygenated taxane flux may enhance photosynthetic electron transfer efficiency and central metabolism in the engineered strain to ameliorate the metabolic disturbances triggered by the incorporation of exogenous genes. This is the first demonstration of photosynthetic production of taxadiene-5α-ol from CO2 in cyanobacteria, highlighting the broad prospects of engineered cyanobacteria as bio-solar cell factories for valuable terpenoids production and expanding the ideas for further rational engineering and optimization.

ObjectiveTo examine differences in HIV-related behaviors among college students who are men who have sex with men (MSM) and of different sexual orientations. MethodsA total of 682 MSM students aged ≥18 years were recruited from colleges/universities in four cities (Hangzhou, Ningbo, Jiaxing and Jinhua) in Zhejiang province through convenience sampling with the help of NGO (non-governmental organization) for a web-based on-site survey with face-to-face instructions from interviewers from March to July 2022. Participants' information on household registration, campus location, years in college, public expression of sexual identity, online casual sex, substance abuse, HIV knowledge, pre-exposure and post-exposure prophylaxis, and HIV testing were collected using a self-compiled questionnaire. SPSS 25.0 software was used for data analysis. ResultsOf the 671 valid respondents, 73.3% reported a homosexual orientation and 26.7% reported a bisexual/unsure orientation. Compared to respondents with a homosexual orientation, respondents with a bisexual/uncertain orientation reported significantly lower rates of publicly expressing their sexual identity (50.8% vs. 60.2%), receiving health education about condom use from peers (70.9% vs. 79.1%), and self-testing for HIV once or more (64. 4% vs. 76.0%), but significantly higher rates of first homosexual behavior within the past year (48.8% vs. 37.4%), being seduced or coerced into first homosexual behavior (27.4% vs. 16.5%), and using sex-stimulating rush popper during their last online casual sexual encounter (40.7% vs. 27.1%) (P < 0.05 for all). ConclusionThere are significant differences between MSM college/university students with a homosexual orientation and those with a bisexual/unsure orientation in public expression of sexual identity, timing and type of first homosexual encounter, use of rush popper and other substances, receipt of peer education about condom use, and self-testing for HIV, suggesting that targeted interventions to reduce the risk of HIV infection in this population should be strengthened.

BackgroundMen who have sex with men (MSM) are increasingly using the internet to meet casual sexual partners. Those who do are at higher risk of sexually transmitted diseases. However, little is known about the rates and associations of frequent HIV testing and self-testing among such MSM. ObjectiveWe aimed to examine HIV serostatus communication and perceptions regarding the HIV infection risk of internet-based partners, along with their associations with frequent HIV testing and self-testing. MethodsA cross-sectional study was conducted between May 2018 and April 2019 in Zhejiang Province, China. The study participants were assigned male at birth, were aged 18 years or older, had had casual sex with another male found through the internet in the last 6 months, and were HIV-negative. Information was obtained on HIV-testing behavior, along with demographic characteristics, HIV-related knowledge, internet-based behaviors, sexual behaviors with male partners, HIV serostatus communication, and perceptions regarding the HIV infection risk of internet-based partners. Uni- and multivariate logistic regression models were used to measure the associations of HIV testing and self-testing. ResultsThe study recruited 281 individuals who had sought casual sexual partners through the internet during the previous 6 months. Of the participants, 61.9% (174/281) reported frequent HIV testing (twice or more frequently) and 50.9% (119/234; 47 with missing values) reported frequent HIV self-testing. MSM who always or usually communicated about the HIV serostatus of internet-based partners in the previous 6 months had 3.12 (95% CI 1.76-5.52) and 2.45 (95% CI 1.42-4.22) times higher odds of being frequently tested or self-tested for HIV, respectively, compared with those who communicated about this issue minimally or not at all. ConclusionsThere remains a need to improve the frequency of HIV testing and self-testing among internet-based MSM. HIV serostatus communication should be improved within the context of social networking applications to promote frequent HIV testing among internet-based MSM, especially for those who communicated about this issue minimally or not at all.

Introduction Post-intensive care syndrome (PICS) seriously affects the quality of life of intensive care unit (ICU) survivors, their ability to return to work and society and the quality of life of their families, increasing overall care costs and healthcare expenditures. ICU follow-up services have important potential to improve PICS. However, the best clinical practice model of ICU follow-up service has not been fully defined and its benefits for ICU survivors are not clear. This review will synthesise and map the current types of follow-up services for ICU survivors and summarise the impact of follow-up services on PICS.Methods and analysis This scoping review will be conducted by applying the five-stage protocol proposed by Arksey and O’Malley in an updated version of the Joanna Briggs Institute. Eight academic databases including the Cochrane Library, MEDLINE, Web of Science, Embase, EBSCO Academic, CINAHL, PsycInfo and SinoMed (China Biology Medicine) will be systematically searched from inception to the present. Peer-reviewed literature and grey literature will be included. Qualitative, quantitative and mixed methods studies will be included. Studies published in English or Chinese will be included. There will be no time restriction. Two reviewers will screen and select the articles independently and if there is any disagreement, the two reviewers will discuss or invite a third reviewer to make decisions together. Descriptive analysis will be used to conduct an overview of the literature. The results will be presented in a descriptive format in response to the review questions accompanied by the necessary tables or charts.Ethics and dissemination Ethical approval is not required for this scoping review because data could be obtained by reviewing published primary study results and do not involve human participants. Findings should be disseminated at scientific meetings and published in peer-reviewed journals.

ABSTRACT Pathogen infections remain a significant public health problem worldwide. Accumulating evidence regarding the crosstalk between bile acid (BA) metabolism and immune response reveals that BA metabolism regulates host immunity and microbial pathogenesis, making it an attractive target for disease prevention and infection control. However, the effect of infection on circulating BA profiles, the biosynthesis-related enzymes, and their receptors remains to be depicted. Here, we investigated the effect of viral (vesicular stomatitis virus, VSV) and bacterial (lipopolysaccharide, LPS) infections on BA metabolism and signaling. Infection models were successfully established by intraperitoneally injecting VSV and LPS, respectively. VSV and LPS injection significantly changed the circulating BA profiles, with highly increased levels of taurine-conjugated BAs and significant decreases in unconjugated BAs. Consistent with the decreased levels of circulating cholic acid (CA) and chenodeoxycholic acid (CDCA), the expression of BA biosynthesis-related rate-limiting enzymes (Cyp7a1, Cyp27a1, Cyp8b1, and Hsd3b7) were significantly reduced. Furthermore, hepatic and pulmonary BA receptors (BARs) expression varied in different infection models. LPS treatment had an extensive impact on tested hepatic and pulmonary BARs, resulting in the upregulation of TGR5, S1PR2, and VDR, while VSV infection only promoted VDR expression. Our study provides insights into the involvement of BA metabolism in the pathophysiology of infection, which may provide potential clues for targeting BA metabolism and BAR signaling to boost innate immunity and control infection.IMPORTANCEThis study focuses on the crosstalk between bile acid (BA) metabolism and immune response in VSV infection and LPS treatment models and depicts the effect of infection on circulating BA profiles, the biosynthesis-related enzymes, and their receptors. These findings provide insights into the effect of infection on BA metabolism and signaling, adding a more comprehensive understanding to the relationship between infection, BA metabolism and immune responses.

Abstract Catalytic activation of Caryl‐O bonds is considered as a powerful strategy for the production of aromatics from lignin. However, due to the high reduction potentials of diaryl ether 4‐O‐5 linkage models, their single electron reduction remains a daunting challenge. This study presents the blue light‐induced bifunctional N‐heterocyclic carbene (NHC)‐catalyzed one‐electron reduction of diaryl ether 4‐O‐5 linkage models for the synthesis of trivalent phosphines. The H‐bond between the newly devised bifunctional NHC and diaryl ethers is responsible for the success of the single electron transfer. Furthermore, this approach demonstrates selective one‐electron reduction of unsymmetric diaryl ethers, oligomeric phenylene oxide, and lignin model.

Objective: This study explores the correlation between Forkhead box M1 (FOXM1) and ATP-binding cassette subfamily C member 5 (ABCC5) in relation to paclitaxel resistance in cervical cancer. It aims to identify potential cervical cancer stem cell markers, offering fresh perspectives for developing therapeutic strategies to overcome paclitaxel chemoresistance in cervical cancer. Methods: Paclitaxel-resistant Hela cells (Hela/Taxol) were developed by intermittently exposing Hela cells to progressively increasing concentrations of paclitaxel. We assessed the biological properties of both Hela and Hela/Taxol cells using various assays: cell proliferation, clonogenic, cell cycle, apoptosis, scratch, and transwell. To determine which markers better represent tumor stem cells, we analyzed various known and potential stem cell markers in combination. Flow cytometry was employed to measure the proportion of positive markers in both parental and drug-resistant cell lines. Following statistical analysis to establish relative stability, CD133+ABCC5+ cells were sorted for further examination. Subsequent tests included sphere-forming assays and Western blot analysis to detect the presence of the stem cell-specific protein Sox2, aiding in the identification of viable cervical cancer stem cell markers. Results: The Hela/Taxol cell line exhibited significantly enhanced proliferation, migration, and invasion capabilities compared to the Hela cell line, alongside a marked reduction in apoptosis rates (P

With the rapid development and wide application of visible (VIS) and infrared (IR) detections, it is necessary to explore visible-infrared (VIS-IR) compatible camouflage. Here, we report a VIS-IR compatible and independent camouflage device which is composed of the upper IR-transparent VIS-color-patterned layer and the lower electrochromic IR layer. The upper layer has amorphous photonic structure of polystyrene nanospheres (PSNSs). By customizing the PSNS size, various colors can be realized for VIS camouflage. The lower electrochromic IR layer takes advantage of multiwall carbon nanotubes (MWCNTs) as the electrode as well as the IR active material. Experimental results reveal that different colors (including blue, green, and purple) have been obtained, and the IR emissivity can be electrically regulated from 0.43 to 0.9. Moreover, the prototype also exhibits good electrical stability as well as hydrophobic characteristic (the water contact angle of the outmost surface exceeds 120°). These output performances demonstrate the success of our design strategy for promoting the finding applied in camouflage fields as well as energy conservation fields.

Abstract Background Microtia is reported to be one of the most common congenital craniofacial malformations. Due to the complex etiology and the ethical barrier of embryonic study, the precise mechanisms of microtia remain unclear. Here we report a rare case of microtia with costal chondrodysplasia based on bioinformatics analysis and further verifications on other sporadic microtia patients. Results One hundred fourteen deleterious insert and deletion (InDel) and 646 deleterious SNPs were screened out by WES, candidate genes were ranked in descending order according to their relative impact with microtia. Label-free proteomic analysis showed that proteins significantly different between the groups were related with oxidative stress and energy metabolism. By real-time PCR and immunohistochemistry, we further verified the candidate genes between other sporadic microtia and normal ear chondrocytes, which showed threonine aspartase, cadherin-13, aldolase B and adiponectin were significantly upregulated in mRNA levels but were significantly lower in protein levels. ROS detection and mitochondrial membrane potential (∆ Ψ m) detection proved that oxidative stress exists in microtia chondrocytes. Conclusions Our results not only spot new candidate genes by WES and label-free proteomics, but also speculate for the first time that metabolism and oxidative stress may disturb cartilage development and this might become therapeutic targets and potential biomarkers with clinical usefulness in the future.

Residual stress plays a pivotal role in assessing the surface quality of machined components, influencing characteristics such as fatigue performance, corrosion resistance, and mechanical strength. Ti6Al4V, a critical material in the nuclear sector, the generation of residual stresses during machining has attracted significant attention. A model for variable friction coefficient model is proposed to accurately characterize the complex plastic deformation behavior of the material. This model takes into account variables such as the relative sliding velocity, contact pressure, and temperature. A subroutine has been developed using the VFRIC interface to enhance precise cutting simulation and modeling. Using the friction model, a new hybrid prediction model for surface residual stresses is developed by integrating finite element analysis and analytical methods. The reliability of both the hybrid and friction models is confirmed through the evaluation of cutting forces, chip morphology, and residual stress. The findings suggest that the novel friction model produces simulation results with higher accuracy compared to traditional Coulomb friction models. The variations in cutting force amount to 5.8% and 13.7%, the error in chip serration is 12.4%, and the deviation in predicting the maximum residual compressive stress is 10.3%. This study contributes to the advancement of friction models and methodologies used in predicting residual stress.

Abstract Background Renal fibrosis is a prevalent manifestation of chronic kidney disease (CKD), and effective treatments for this disease are currently lacking. Myofibroblasts, which originate from interstitial fibroblasts, aggregate in the renal interstitium, leading to significant accumulation of extracellular matrix and impairment of renal function. The nonreceptor tyrosine kinase c-Abl (encoded by the Abl1 gene) has been implicated in the development of renal fibrosis. However, the precise role of c-Abl in this process and its involvement in fibroblast-myofibroblast transition (FMT) remain poorly understood. Methods To investigate the effect of c-Abl in FMT during renal fibrosis, we investigated the expression of c-Abl in fibrotic renal tissues of patients with CKD and mouse models. We studied the phenotypic changes in fibroblast or myofibroblast-specific c-Abl conditional knockout mice. We explored the potential targets of c-Abl in NRK-49F fibroblasts. Results In this study, fibrotic mouse and cell models demonstrated that c-Abl deficiency in fibroblasts mitigated fibrosis by suppressing fibroblast activation, fibroblast-myofibroblast transition, and extracellular matrix deposition. Mechanistically, c-Abl maintains the stability of the RACK1 protein, which serves as a scaffold for proteins such as c-Abl and focal adhesion kinase at focal adhesions, driving fibroblast activation and differentiation during renal fibrosis. Moreover, specifically targeting c-Abl deletion in renal myofibroblasts could prove beneficial in established kidney fibrosis by reducing RACK1 expression and diminishing the extent of fibrosis. Conclusions Our findings suggest that c-Abl plays a pathogenic role in interstitial fibrosis through the regulation of RACK1 protein stabilization and myofibroblast differentiation, suggesting a promising strategy for the treatment of CKD.

Abstract Phase singularities are phase-indeterminate points where wave amplitudes are zero, which manifest as phase vertices or wavefront dislocations. In the realm of optical and electron beams, the phase singularity has been extensively explored, demonstrating a profound connection to orbital angular momentum. Direct local imaging of the impact of orbital angular momentum on phase singularities at the nanoscale, however, remains challenging. Here, we study the role of orbital angular momentum in phase singularities in graphene, particularly at the atomic level, through scanning tunneling microscopy and spectroscopy. Our experiments demonstrate that the scatterings between different orbital angular momentum states, which are induced by local rotational symmetry-breaking potentials, can generate additional phase singularities, and result in robust single-wavefront dislocations in real space. Our results pave the way for exploring the effects of orbital degree of freedom on quantum phases in quasiparticle interference processes.

Abstract Background Primary cardiac angiosarcoma(PCA) has a low incidence rate and poor prognosis. Currently, no unified clinical treatment standards are available. Case presentation We report the case of a 48-year-old man presenting chest tightness, breathlessness, and dyspnea. Imaging and postoperative histopathologic studies confirmed PCA and that the tumor had invaded the entire right atrium. The patient developed progressive disease (PD) during postoperative radiotherapy. We used immunotherapy combined with targeted therapy based on the results of molecular profile and evaluation of tertiary lymphoid structures (TLSs) and programmed cell death-ligand 1 (PD-L1). After treatment, the metastatic lymph nodes of the patient were reduced to a certain extent, indicating that combination therapy was effective. Conclusion To the best of our knowledge, this is the first report of radiotherapy combined with anti-PD-1 and tyrosine kinase inhibitors(TKI) for PCA. In addition, this is the first report on immunotherapy for PCA based on new evaluation methods, including TLSs, PD-L1, and genomic profile.

Abstract Background Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. Methods DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. Results The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. Conclusion KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

Abstract The precise structural integration of single-atom and high-entropy-alloy features for energy electrocatalysis is highly appealing for energy conversion, yet remains a grand challenge. Herein, we report a class of single-atom Mo-tailored PdPtNiCuZn high-entropy-alloy nanosheets with dilute Pt-Pt ensembles and intrinsic tensile strain (Mo1-PdPtNiCuZn) as efficient electrocatalysts for enhancing the methanol oxidation reaction catalysis. The as-made Mo1-PdPtNiCuZn delivers an extraordinary mass activity of 24.55 A mgPt −1 and 11.62 A mgPd+Pt −1, along with impressive long-term durability. The planted oxophilic Mo single atoms as promoters modify the electronic structure of isolated Pt sites in the high-entropy-alloy host, suppressing the formation of CO adsorbates and steering the reaction towards the formate pathway. Meanwhile, Mo promoters and tensile strain synergistically optimize the adsorption behaviour of intermediates to achieve a more energetically favourable pathway and minimize the methanol oxidation reaction barrier. This work advances the design of atomically precise catalytic sites by creating a new paradigm of single atom-tailored high-entropy alloys, opening an encouraging pathway to the design of CO-tolerance electrocatalysts.

Residual stress is an important surface integrity index to evaluate the crack initiation and failure of die surface. The efficient prediction of cutting residual stress can guide the high-quality machining of die and improve its service life. The existing cutting residual stress prediction models are complex, time-consuming and inefficient. In this paper, a hybrid prediction method of cutting residual stress based on finite element-analytical-neural network is proposed. Firstly, the stress, strain and temperature of the cutting surface are obtained based on the orthogonal cutting finite element model. Then, the stress relaxation analytical algorithm considering the elastic-plastic state of the material is used to replace the stress release process of the finite element, and the residual stress distribution data were obtained based on the joint model of finite element and analytical algorithm. Secondly, the surrogate model of BP neural network (SSA-BP) is improved based on SSA algorithm to realize the rapid prediction of characteristic value of residual stress. The effectiveness of the finite element-analytical-neural network hybrid model was verified by the cutting residual stress test of H13 steel. Finally, the effects of tool structure parameters and cutting parameters on the residual stress distribution and the maximum compressive stress and maximum tensile stress of H13 steel were studied. This method can provide a flexible and efficient basic model for obtaining the optimal cutting conditions for controlling the residual stress of H13 steel and other metals.

Background: Men who have sex with men (MSM) are a significant population contributing to human immunodeficiency virus (HIV) transmission. Nevertheless, few studies have focused on the heterogeneity in MSM. The characteristics of men who have sex with men and women (MSMW) may differ from men who have sex with men only (MSMO). Methods: From October 2022 to March 2023, a cross-sectional study for MSM was conducted in Eastern China. An electronic questionnaire was used to collect the demographic characteristics and sexual behaviors of participants. A multivariable logistic regression model was used to assess the differences in HIV-related risky sexual behaviors between MSMO and MSMW. Results: A total of 1993 MSM were enrolled in the study, with 1221 MSMO and 772 MSMW. Compared to MSMW, MSMO reported younger age at first anal sex, higher coerced homosexual experiences, and observed different characteristics of sexual behavior in the past six months. Multivariable analysis indicated that MSMW were more likely to seek casual partners and use stimulants online and offline. MSMW showed inconsistent condom use with online partners (aOR = 0.51, 95 %CI: 0.38–0.68) and more frequent anal sex after drinking (aOR = 2.27, 95 %CI: 1.54–3.35). They also had higher risks of commercial (aOR = 2.47, 95 %CI: 1.71–3.57) and group sexual behaviors (aOR = 1.88, 95 %CI: 1.24–2.83) compared to MSMO. Conclusion: Our findings suggest that the differential factors may lead MSMW to become a subgroup at high risk of HIV infection. The gender identity and sexual orientation within MSM should be considered when formulating acquired immune deficiency syndrome (AIDS) prevention and control strategies.

Abstract Precise control of quantum structures in hybrid nanocrystals requires advancements in scientific methodologies. Here, on the design of tunable CsPbBr3/Cs4PbBr6 quantum dots are reported by developing a unique discrete phase transformation approach in Cs4PbBr6 nanocrystals. Unlike conventional hybrid systems that emit solely in the green region, this current strategy produces adjustable luminescence in the blue (450 nm), cyan (480 nm), and green (510 nm) regions with high photoluminescence quantum yields up to 45%, 60%, and 85%, respectively. Concentration‐dependent studies reveal that phase transformation mechanisms and the factors that drive CsBr removal occur at lower dilutions while the dissolution–recrystallization process dominates at higher dilutions. When the polymer‐CsPbBr3/Cs4PbBr6 integrated into a field‐effected transistor the resulting phototransistors featured enhanced photosensitivity exceeding 105, being the highest reported for an n‐type phototransistor, while maintaining good transistor performances as compared to devices consisting of polymer‐CsPbBr3 NCs.

PurposeRadiation encephalopathy (REP) is one of the most common complications of radiotherapy for malignant tumors of the head and neck. Symptoms usually appear months to years following radiotherapy, with headache, insomnia, and memory loss as the main clinical features. We report a patient who was admitted to the hospital with anxiety and depressive disorder and was eventually diagnosed with REP.Patients and methodsA 48-year-old patient who had undergone over 2 years of radiotherapy for nasopharyngeal carcinoma was admitted to the Department of Psychosomatic Medicine of our hospital because of recurrent fear, low mood, and waking up from dreams. Magnetic resonance imaging (MRI) revealed a mass in the left temporal lobe with a large peripheral edema. After multidisciplinary consultation, the possibility of tumor recurrence could not be excluded.ResultsResection of the lesioned brain tissue to obtain pathological tissue showed glial cell proliferation and small focal areas of degeneration and necrosis, which indicated that the lesions were inflammatory. Postoperative MRI showed no abnormal signal, and the patient’s condition improved.ConclusionNasopharyngeal carcinoma patients with a history of radiotherapy and symptoms of increased intracranial pressure and neurological damage should be examined for REP. Furthermore, patients may experience anxiety and depressive disorders as a result of temporal lobe damage caused by REP.

Background and aimsTranscatheter tricuspid valve replacement (TTVR) has recently emerged as a novel therapeutic approach for managing severe tricuspid regurgitation (TR). However, surgical tricuspid valve replacement (STVR) continues to be the predominant treatment modality. There are limited comparative data on both procedures. This study aimed to compare clinical and echocardiographic outcomes between patients who underwent mini-thoracotomy transatrial LuX-Valve TTVR and those who underwent STVR.MethodsThis study prospectively collected patients with severe TR who underwent TTVR (n = 29) or isolated STVR (n = 59) at Wuhan Union Hospital from 2019 to 2022. All TTVR patients received the LuX-Valve via a mini-thoracotomy and transatrial approach. The clinical and echocardiographic outcomes were compared at 30-day and one-year follow-ups.ResultsAt baseline, patients with LuX-Valve TTVR had higher surgical risk scores and a greater proportion of right ventricular dysfunction compared with STVR. In the early postoperative period, the STVR group had a greater decrease in right ventricular function. Hospital length of stay (LOS), intensive care unit LOS, total procedure time, and tracheal intubation time were shorter in the TTVR than in the STVR group. The incidence of postoperative paravalvular leaks was higher among patients who underwent TTVR. Compared to the STVR group, the pacemaker implantation rate was lower in the TTVR group. During follow-up, the peak tricuspid valve velocity and mean gradient in the TTVR group were consistently lower than those in the STVR group. There was similar mortality between TTVR and STVR at 30-day and one-year follow-ups.ConclusionsThe mini-thoracotomy transatria LuX-Valve TTVR has a higher incidence of paravalvular leaks and a lower rate of pacemaker implantation than STVR, with similar 30-day and one-year mortality rates. In some respects, mini-thoracotomy transatrial LuX-Valve TTVR may be a feasible and safe treatment option for specific populations, or it could potentially serve as an alternative therapy to supplement conventional STVR. Further follow-up is required to assess differences in long-term clinical outcomes and valve durability.

Herein, lutecium silicate is used as a rock example to investigate its two high‐pressure phases (7.4 GPa: HP‐II and 25.3 GPa: HP‐III) and lattice dynamics by in situ high‐pressure Raman scattering up to 35.1 GPa. The evidence for a highly symmetrical insulator HP‐III phase is obtained. Importantly, the high‐pressure structure (metastable phases) after pressure quenching is also intercepted, indicating pressure‐induced permanent densification. These findings provide Raman evidence for pressure‐induced successive phase transitions of highly symmetric insulators intercepted in prototype Lu2SiO5 and physical insights to explain the self‐regulation of rare earth‐rich regions in facilitating highly effective global carbon cycling.

Objective: The primary objective was to investigate whether the utilization of next-generation sequencing (NGS) for preimplantation genetic testing for aneuploidy (PGT-A) could enhance the reproductive outcomes in patients with unexplained recurrent pregnancy loss (uRPL) or unexplained repeated implantation failure (uRIF) undergoing intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: We studied the reproductive outcomes of uRPL or uRIF sufferers in Chengdu women and children's central hospital from July 2020 to Jan 2024 retrospectively. These patients were categorized into two groups based on whether they underwent PGT-A or not. As the patients in the PGT-A group all had ICSI and frozen-thawed embryo transfer (FET), only patients who underwent ICSI and FET were included in the non-PGT-A group for comparison. Demographic characteristics and reproductive outcomes were compared in uRPL or uRIF sufferers. Results: For uRPL group, a significant increased ongoing pregnancy rate (63.6 % vs 26.1 %, p = 0.002) and reduced pregnancy loss rate (18.4 % vs 73.3 %, p

BackgroundAntiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) viral replication and ultimately achieve viral suppression and eliminate HIV transmission. However, little is known about the impact of viral suppression on high-risk behaviors and sexually transmitted infections (STIs).ObjectiveThis study aimed to assess the rates of current syphilis infection in virally suppressed people living with HIV (PLWH) and whether with the duration of ART can reduce the current syphilis infection in eastern China.MethodWe conducted a cross-sectional survey of PLWH in Zhejiang Province, China, in 2022. PLWH who were on ART >6 months and were virally suppressed (viral load

Streptococcus agalactiae (S.agalactiae), also known as group B Streptococcus (GBS), is a highly infectious pathogen. Prolonged antibiotic usage leads to significant issues of antibiotic residue and resistance. Chelerythrine (CHE) is a naturally occurring benzophenidine alkaloid and chelerythrine chloride (CHEC) is its hydrochloride form with diverse biological and pharmacological activities. However, the antibacterial mechanism of CHEC against GBS remains unclear. Thus, this study aims to investigate the in vitro antibacterial activity of CHEC on GBS and elucidate its underlying mechanism. The antibacterial effect of CHEC on GBS was assessed using inhibitory zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays, as well as by constructing a time-kill curve. The antibacterial mechanism of CHEC was investigated through techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), measurement of alkaline phosphatase (AKP) activity, determination of Na+ K+, Ca2+ Mg2+—adenosine triphosphate (ATP) activity, observation of membrane permeability, and analysis of intracellular reactive oxygen species (ROS) and mRNA expression levels of key virulence genes. The results demonstrated that the inhibition zone diameters of CHEC against GBS were 14.32 mm, 12.67 mm, and 10.76 mm at concentrations of 2 mg/mL, 1 mg/mL, and 0.5 mg/mL, respectively. The MIC and MBC values were determined as 256 μg/mL and 512 μg/mL correspondingly. In the time-kill curve, 8 × MIC, 4 × MIC and 2 × MIC CHEC could completely kill GBS within 24 h. SEM and TEM analyses revealed significant morphological alterations in GBS cells treated with CHEC including shrinkage, collapse, and leakage of cellular fluids. Furthermore, the antibacterial mechanism underlying CHEC’s efficacy against GBS was attributed to its disruption of cell wall integrity as well as membrane permeability resulting in extracellular release of intracellular ATP, AKP, Na+ K+, Ca2+ Mg2+. Additionally CHEC could increase the ROS production leading to oxidative damage and downregulating mRNA expression levels of key virulence genes in GBS cells. In conclusion, CHEC holds potential as an antimicrobial agent against GBS and further investigations are necessary to elucidate additional molecular mechanisms.

BackgroundMen who have sex with men (MSM) constitute a significant population of patients infected with HIV. In recent years, several efforts have been made to promote HIV testing among MSM in China. ObjectiveThis study aimed to assess HIV testing coverage and factors associated with first-time HIV testing among MSM to provide a scientific basis for achieving the goal of diagnosing 95% of patients infected with HIV by 2030. MethodsThis cross-sectional study was conducted between July 2023 and December 2023. MSM were recruited from the “Sunshine Test,” an internet platform that uses location-based services to offer free HIV testing services to MSM by visiting the WeChat official account in Zhejiang Province, China. Participants were required to complete a questionnaire on their demographic characteristics, sexual behaviors, substance use, and HIV testing history. A logistic regression model was used to analyze first-time HIV testing and its associated factors. ResultsA total of 7629 MSM participated in the study, with 87.1% (6647) having undergone HIV testing before and 12.9% (982) undergoing HIV testing for the first time. Multivariate logistic regression analysis revealed that first-time HIV testing was associated with younger age (adjusted odds ratio [aOR] 2.55, 95% CI 1.91-3.42), lower education (aOR 1.39, 95% CI 1.03-1.88), student status (aOR 1.35, 95% CI 1.04-1.75), low income (aOR 1.55, 95% CI 1.16-2.08), insertive anal sex role (aOR 1.28, 95% CI 1.05-1.56), bisexuality (aOR 1.69, 95% CI 1.40-2.03), fewer sex partners (aOR 1.44, 95% CI 1.13-1.83), use of rush poppers (aOR 2.06, 95% CI 1.70-2.49), unknown HIV status of sex partners (aOR 1.40, 95% CI 1.17-1.69), lack of awareness of HIV pre-exposure prophylaxis (aOR 1.39, 95% CI 1.03-1.88), and offline HIV testing uptake (aOR 2.08, 95% CI 1.80-2.41). ConclusionsA notable 12.9% (982/7629) of MSM had never undergone HIV testing before this large internet survey. We recommend enhancing HIV intervention and testing through internet-based platforms and gay apps to promote testing among MSM and achieve the target of diagnosing 95% of patients infected with HIV by 2030.

BackgroundAs a therapeutic tool, kinesiology taping (KT) has become increasingly popular for musculoskeletal injuries utilized by physiotherapists. KT has been found to have effects on facilitating muscle strength by generating a concentric pull on the fascia. However, little is known about KT in the improvement of dynamic and static balance. This study aims to explore whether KT on the quadriceps muscle has any immediate effects on static and dynamic balance.MethodologyTwenty-seven healthy individuals (13 males and 14 females, aged 22 to 29) were recruited in a crossover study with two conditions: KT and no taping. KT was applied to the quadriceps muscle for the taping group, with the control receiving no taping. Pre- and post-test measurements were taken to give an indication of the effect of the tape on balance performance. Center of Pressure Excursion (COPE) and Time to Stabilization (TTS) when landing from a hop test and Y Balance test combined score (YBTCS) were used to assess a stabilizing balance activity and a dynamic balance. The pre- and post-intervention were collected, with differences explored using repeated measures ANOVA with time and condition (tape) factor analysis.ResultsWe found a significant improvement (p ≤ 0.05) with a moderate to large effect size in YBTCS between KT and no taping, indicating enhanced balance performance in the KT group. However, no significant difference (p ≥ 0.05) with small to moderate effect size was found in COPE or TTS between the two conditions during landing tests, suggesting similar balance capabilities in these specific measures.ConclusionThe use of KT shows no significant immediate effect on static balance in healthy individuals when applied to the quadriceps muscles; however, it demonstrates a positive immediate effect on dynamic balance.

Abstract Background Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P

Zenith tropospheric delay (ZTD), consisting of zenith hydrostatic delay (ZHD) and zenith wet delay (ZWD), is a significant contributor to errors in precise positioning using the global navigation satellite system (GNSS) precise point positioning (PPP) and real-time kinematic techniques. Accurate and timely predictions of ZTD on a global scale are crucial for enhancing GNSS positioning accuracy and expediting convergence. This study proposes an innovative global tropospheric prediction model that leverages long short-term memory (LSTM) neural networks, aiming to achieve both high precision and long-term prediction capability for ZTD. The experimental data utilized were sourced from the Vienna Mapping Functions 3-Optimized zenith total delay (ZTD) dataset. This study delves further into the analysis of ZTD residuals by extracting periodic signals. The ZTD residuals were then utilized to train a modified LSTM neural network model, enabling the prediction of global residuals. The final ZTD predictions were obtained by combining the modified LSTM ZTD residual forecast component with the ZTD periodic component. Our results demonstrate that the average root-mean-square error (RMSE) of the modified LSTM-ZTD model in 2020 was 1.44 cm. In addition, the average RMSE of the forecasted ZTD during spring, summer, autumn, and winter was found to be 1.43 cm, 1.47 cm, 1.56 cm, and 1.36 cm, respectively. Through the integration of the LSTM neural network and the ZTD periodic signal extracted using a physical algorithm, this work has successfully enhanced the accuracy and time span of ZTD forecasts on a global scale.

Brain-computer interfaces (BCIs) are anticipated to improve the efficacy of rehabilitation for people with motor disabilities. However, applying BCI in clinical practice is still a challenge due to the great diversity of patients. In the current study, a novel action observation (AO) based BCI was proposed and tested on stroke patients. Ten non-hemineglect patients and ten hemineglect patients were recruited. Four AO stimuli were designed, each presenting a decomposed action to complete the reach-and-grasp task. EEG data and eye movement data were collected. Eye movement data was utilized to analyze the reasons for individual differences in BCI performance. Task discriminative component analysis was utilized to perform online target detection. The results showed that the designed AO-based BCI could simultaneously induce steady state motion visual evoked potential (SSMVEP) from the occipital region and sensory motor rhythm from the sensorimotor region in stroke patients. The average online detection accuracy among the four AO stimuli reached 67% within 3 s in the non-hemineglect group, while the accuracy only reached 35% in the hemineglect group. Gaze metrics showed that the average total duration of fixations during the stimulus phase in the hemineglect group was only 1.31 s ± 0.532 s which was significantly lower than that in the non-hemineglect group. The results indicated that hemineglect patients have difficulty gazing at the AO stimulus, resulting in poor detection performance and weak desynchronization in the sensorimotor region. Furthermore, the degree of neglect is inversely proportional to the target detection accuracy in hemineglect stroke patients. In addition, the gaze metrics associated with cognitive load were significantly correlated with the accuracy in non-hemineglect patients. It indicated the cognitive load may affect the AO-based BCI. The current study will expedite the clinical application of AO-based BCI.

In order to address the problem of incomplete data set of real seismic impact of cultural relics in collections, we propose a small sample set oriented center-of-mass positioning method to solve the center-of-mass attribute of cultural relics ontology. First, the method combines the cultural relics image data to construct a deep feature fusion cultural relics ontology recognition model, which extracts and learns the cultural relics image features through multi-layer feature extraction, global information perception and ontology fusion recognition, so as to realize the efficient and accurate recognition of the cultural relic’s ontology. Then, the parameter synchronous migration learning method is designed to train and initialize the model, and the data migration strategy of semi-supervised learning is used to retrain the model using the public dataset and the cultural relic image data, to achieve the fine-tuning of the model parameters to improve the accuracy of the cultural relic ontology recognition. Finally, the center-of-mass positioning method is designed to integrate the attention mechanism with the quality of relics and other ontological attributes, and the segmentation of the relic’s ontology region is achieved by rectangular stereo fitting and the calculation of the center-of-mass points. At the same time, the fusion self-attention mechanism is used to adjust the regional center-of-mass weights to achieve weighted positioning of the center-of-mass position of the cultural relics. The experimental results show that the present method achieves the best Dice, Acc and MIoU metrics in comparison with various classical models, with improvements of 8.3%, 5.1% and 3.4% respectively. The overall center-of-mass offset of cultural relics is less than 2%, which can achieve accurate identification and center-of-mass positioning of the cultural relics body, fully improve the seismic impact dataset of cultural relics, and enhance the ability of preventive protection of cultural relics against earthquakes.

Hyperspectral (HS) pansharpening refers to fusing low spatial resolution HS (LRHS) images with the corresponding panchromatic (PAN) images to create high spatial resolution HS (HRHS) images. Most of the existing HS pansharpening methods overlook the spatial and spectral imbalance of the ground objects of different types in the observed scenes. To address the dilemma, in this article we develop a novel tree-structured neural network (Tree-SNet) to form an adaptive spatial-spectral processing for HS pansharpening. The Tree-SNet method maps a convolutional neural network (CNN) onto a hierarchical tree structure, where routing nodes automatically tune the data distributed to tree paths, which is adaptive to the local characteristics of the data, while spatial enhancement (SpatE) and spectral enhancement (SpecE) modules are dynamically performed in the tree paths to further strengthen the adaptive processing. The proposed Tree-SNet is evaluated on several datasets, and the experimental results verify its superiority.

Background: Myocardial Infarction (MI) and severe mental disorders (SMDs) are two types of highly prevalent and complex disorders and seem to have a relatively high possibility of mortality. However, the contributions of common and rare genetic variants to their comorbidity arestill unclear. Methods: We conducted a combined genome-wide association study (GWAS) and exome-wide association study (EWAS) approach. Results: Using gene-based and gene-set association analyses based on the results of GWAS, we found the common genetic underpinnings of nine genes (GIGYF2, KCNJ13, PCCB, STAG1, HLA-C, HLA-B, FURIN, FES, and SMG6) and nine pathways significantly shared between MI and SMDs. Through Mendelian randomization analysis, we found that twenty-seven genes were potential causal genes for SMDs and MI. Based on the exome sequencing data of MI and SMDs patients from the UK Biobank, we found that MUC2 was exome-wide significant in the two diseases. The gene-set analyses of the exome-wide association study indicated that pathways related to insulin processing androgen catabolic process and angiotensin receptor binding may be involved in the comorbidity between SMDs and MI. We also found that six candidate genes were reported to interact with known therapeutic drugs based on the drug–gene interaction information in DGIdb. Conclusions: Altogether, this study revealed the overlap of common and rare genetic underpinning between SMDs and MI and may provide useful insights for their mechanism study and therapeutic investigations.

ObjectivesTo investigate the association between contrast-enhanced ultrasound (CEUS) features of PTC and central lymph node metastasis (CLNM) and to develop a predictive model for the preoperative identification of CLNM.MethodsThis retrospective study evaluated 750 consecutive patients with PTC from August 2020 to April 2023. Conventional ultrasound and qualitative CEUS features were analyzed for the PTC with or without CLNM using univariate and multivariate logistic regression analysis. A nomogram integrating the predictors was constructed to identify CLNM in PTC. The predictive nomogram was validated using a validation cohort.ResultsA total of 684 patients were enrolled. The 495 patients in training cohort were divided into two groups according to whether they had CLNM (pCLNM, n= 191) or not (nCLNM, n= 304). There were significant differences in terms of tumor size, shape, echogenic foci, enhancement direction, peak intensity, and score based on CEUS TI-RADS between the two groups. Independent predictive US features included irregular shape, larger tumor size (≥ 1.0cm), and score. Nomogram integrating these predictive features showed good discrimination and calibration in both training and validation cohort with an AUC of 0.72 (95% CI: 0.68, 0.77) and 0.79 (95% CI: 0.72, 0.85), respectively. In the subgroup with larger tumor size, age ≤ 35 years, irregular shape, and score > 6 were independent risk factors for CLNM.ConclusionThe score based on preoperative CEUS features of PTC may help to identify CLNM. The nomogram developed in this study provides a convenient and effective tool for clinicians to determine an optimal treatment regimen for patients with PTC.

Epigenetic modifications, including DNA methylation and histone post-translational modifications, intricately regulate gene expression patterns by influencing DNA accessibility and chromatin structure in higher organisms. These modifications are heritable, are independent of primary DNA sequences, undergo dynamic changes during development and differentiation, and are frequently disrupted in human diseases. The reversibility of epigenetic modifications makes them promising targets for therapeutic intervention and drugs targeting epigenetic regulators (e.g., tazemetostat, targeting the H3K27 methyltransferase EZH2) have been applied in clinical therapy for multiple cancers. The NSD family of H3K36 methyltransferase enzymes—including NSD1 (KMT3B), NSD2 (MMSET/WHSC1), and NSD3 (WHSC1L1)—are now receiving drug development attention, with the exciting advent of an NSD2 inhibitor (KTX-1001) advancing to Phase I clinical trials for relapsed or refractory multiple myeloma. NSD proteins recognize and catalyze methylation of histone lysine marks, thereby regulating chromatin integrity and gene expression. Multiple studies have implicated NSD proteins in human disease, noting impacts from translocations, aberrant expression, and various dysfunctional somatic mutations. Here, we review the biological functions of NSD proteins, epigenetic cooperation related to NSD proteins, and the accumulating evidence linking these proteins to developmental disorders and tumorigenesis, while additionally considering prospects for the development of innovative epigenetic therapies.

The razor clam Sinonovacula constricta, is one of the most commercially important cultured bivalves in China and Southeast Asia, while S. rivularis is its closer relatives discovered more than a decade ago. In order to obtain offspring with faster growth rate and stronger salt tolerance of S. constricta and S. rivularis, interspecific hybrids were produced, and the hybridity of the interspecific hybrids was confirmed by microsatellite markers. Microsatellite markers exhibit a high potential for transfer through cross-amplification in related species, and the transferability of 48 pairs of microsatellite marker primers from S. constricta were assessed in S. rivularis. Here, 24 universal microsatellite markers were successfully amplified in S. rivularis, of which 18 were polymorphic with the allele number from 2 to 5. The genetic diversity of two razor clams evaluated by 18 polymorphic microsatellite markers indicated that two species were both above the middle level, with a relatively higher genetic diversity, while S. constricta showed higher genetic diversity than S. rivularis according to the genetic parameters of Na, Ho, He and PIC. Furthermore, a total of two species-specific microsatellite markers were screened, which could be used for quick genetic identification of S. constricta, S. rivularis and their hybrids. The results suggest the induced interspecific hybrids are true hybrids between S. constricta and S. rivularis, which provide a basis for breeding, subsequent protection, and germplasm resources utilization of the razor clams.

Background and objectives: The neutrophil-to-lymphocyte ratio (NLR) is a widely recognized marker of inflammation in peripheral blood. However, its specific role in neuronal intranuclear inclusion disease (NIID) has not been reported. This study aims to investigate the relationship between NIID and NLR. Methods: A multicenter database was collected, including 157 NIID patients from seven hospitals (The Affiliated Hospital of Xuzhou Medical University, Yantai Yuhuangding Hospital, Tengzhou Central People's Hospital,The Affiliated Brain Hospital of Nanjing Medical University, Liaocheng People's Hospital,The Second Hospital of Shandong University, Inner Mongolia People's Hospital, Xuanwu Hospital Capital Medical University,The First Affiliated Hospital of USTC), along with 157 age- and gender-matched healthy control subjects. White blood cell counts (including neutrophils, lymphocytes, monocytes, eosinophils, and basophils) were obtained, and the NLR was calculated. Additionally, cognitive impairment was assessed using clinical evaluation scores. Results: NIID patients exhibited significantly higher NLR values compared to the healthy control group (p 0.05). Conclusion: There is a significant association between NLR and NIID, suggesting a potential role of peripheral blood inflammation in the pathogenesis of NIID.

BackgroundThe worldwide human monkeypox (mpox) outbreak in 2022 mainly affected men who have sex with men (MSM). In China, young men who have sex with men (YMSM) were at a potential high risk of mpox infection due to their sexual activeness and the eased COVID-19 restrictions at the end of 2022. ObjectiveThis study aimed to investigate the behavioral intention of receiving mpox vaccination and undergoing mpox testing in 4 different scenarios and explore their associations with background and behavioral theory–related factors among Chinese YMSM. MethodsAn online cross-sectional survey was conducted among YMSM aged 18-29 years from 6 representative provinces of China in September 2022. Participants recruited (recruitment rate=2918/4342, 67.2%) were asked to self-administer an anonymous questionnaire designed based on prior knowledge about mpox and classic health behavior theories. Data on the participants’ background, mpox knowledge and cognition, mpox vaccination and testing cognition, and the behavioral intention of receiving mpox vaccination and undergoing mpox testing were collected. Descriptive analysis and univariate and multivariate linear regressions were performed. Geodetector was used to measure the stratified heterogeneity of behavioral intention. ResultsA total of 2493 YMSM with a mean age of 24.6 (SD 2.9) years were included. The prevalence of having a behavioral intention of receiving mpox vaccination ranged from 66.2% to 88.4% by scenario, varying in epidemic status and cost. The prevalence of having an mpox testing intention was above 90% in all scenarios regardless of the presence of symptoms and the cost. The positive factors related to vaccination intention included mpox knowledge (ba=0.060, 95% CI 0.016-0.103), perceived susceptibility of mpox (ba=0.091, 95% CI 0.035-0.146), perceived severity of mpox (ba=0.230, 95% CI 0.164-0.296), emotional distress caused by mpox (ba=0.270, 95% CI 0.160-0.380), perceived benefits of mpox vaccination (ba=0.455, 95% CI 0.411-0.498), self-efficacy of mpox vaccination (ba=0.586, 95% CI 0.504-0.668), and having 1 male sex partner (ba=0.452, 95% CI 0.098-0.806), while the negative factor was perceived barriers to vaccination (ba=–0.056, 95% CI –0.090 to –0.022). The positive factors related to testing intention were perceived severity of mpox (ba=0.283, 95% CI 0.241-0.325), perceived benefits of mpox testing (ba=0.679, 95% CI 0.636-0.721), self-efficacy of mpox testing (ba=0.195, 95% CI 0.146-0.245), having 1 male sex partner (ba=0.290, 95% CI 0.070-0.510), and having in-person gatherings with MSM (ba=0.219, 95% CI 0.072-0.366), while the negative factor was emotional distress caused by mpox (ba=–0.069, 95% CI –0.137 to –0.001). ConclusionsAmong Chinese YMSM, the intention of undergoing mpox testing is optimal, while the mpox vaccination intention has room for improvement. A future national response should raise YMSM’s mpox knowledge, disseminate updated information about mpox and preventive measures, improve preventive service accessibility and privacy, and provide advice on positively coping with the associated emotional distress.

Mariculture wastewater poses environmental challenges due to pollution and eutrophication. Targeted cultivation of diatoms in wastewater can help alleviate these issues while generating beneficial algae biomass, however reliable operating methods are lacking. We proposed a novel method for treating mariculture wastewater that employed UV-C irradiation and nutrient regulation to achieve targeted diatom cultivation. This study first examined growth of four diatom species (Nitzschia closterium, Chaetoceros muelleri, Cyclotella atomus, and Conticribra weissflogii) in mariculture wastewater. C. muelleri and C. weissflogii demonstrated better adaptability compared to N. closterium and C. atomus. Additionally, the growth and nutrient utilization of C. muelleri were studied under varying concentrations of silicate, phosphate, ammonium, and trace elements in wastewater. Optimal growth was observed at 500 μmol/L silicate, 0.6 mg/L phosphate, and 4 mg/L ammonium. Ammonium proved to be a more effective nitrogen source than urea and nitrate in promoting growth at this low level. Surprisingly, trace element supplementation did not significantly impact growth. Finally, this study utilized UV-C irradiation as a pre-treatment method for wastewater prior to nutrient adjustment, significantly enhancing the growth of C. muelleri. Overall, this study provides guidance on regulating key nutrients and pre-treatment method to optimize diatom biomass production from mariculture wastewater. This approach not only addresses environmental challenges associated with mariculture but also contributes to sustainable aquaculture practices through the recovery of valuable aquatic resources.

Abstract Laryngeal cancer ranks as the second most prevalent upper airway malignancy, following Lung cancer. Although some progress has been made in managing laryngeal cancer, the 5-year survival rate is disappointing. The gradual increase in the incidence of second primary tumors (SPTs) plays a crucial role in determining survival outcomes during long-term follow-up, and the esophagus was the most common site with a worse prognosis. In clinical practice, the treatment of esophageal second primary tumors (ESPT) in patients with laryngeal squamous cell carcinoma (LSCC) has always been challenging. For patients with synchronous tumors, several treatment modalities, such as radiotherapy, chemotherapy and potentially curative surgery are necessary but are typically poorly tolerated. Secondary cancer therapy options for metachronous patients are always constrained by index cancer treatment indications. Therefore, understanding the clonal origin of the second primary tumor may be an important issue in the treatment of patients. LSCC cells demonstrate genetic instability because of two distinct aetiologies (human papillomavirus (HPV)-negative and HPV-positive) disease. Various etiologies exhibit distinct oncogenic mechanisms, which subsequently impact the tissue microenvironment. The condition of the tissue microenvironment plays a crucial role in determining the destiny and clonal makeup of mutant cells during the initial stages of tumorigenesis. This review focuses on the genetic advances of LSCC, the current research status of SPT, and the influence of key carcinogenesis of HPV-positive and HPV-negative LSCC on clonal evolution of ESPT cells. The objective is to gain a comprehensive understanding of the molecular basis underlying the clonal origins of SPT, thereby offering novel perspectives for future investigations in this field.

Abstract Background Female reproductive factors such as age at first birth (AFB), age at last birth (ALB), number of pregnancies and live births play an essential role in women’s health. However, few epidemiological studies have evaluated the association between female reproductive factors and metabolic syndrome (MetS). We therefore conducted a cross-sectional study to investigate the association between MetS risk and female reproductive factors. Methods We investigated the relationship between AFB, ALB, number of pregnancies and live births and the incidence of MetS using publicly available data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Weighted multivariable logistic regression analysis, restricted cubic spline (RCS) model, and subgroup analysis were used to evaluate the association between AFB and ALB and the risk of MetS in women. In addition, the relationship between the number of pregnancies, live births and MetS risk was also explored. Results A total of 15,404 women were included in the study, and 5,983 (38.8%) had MetS. RCS models showed an N-shaped relationship between AFB and MetS risk, whereas ALB, number of pregnancies, and live births were linearly associated with MetS. Weighted multivariable logistic regression analysis showed that the number of live births was associated with MetS risk, with ORs of 1.18 (95% CI: 1.04, 1.35) for women with ≥ 5 deliveries compared to women with ≤ 2 births. Conclusions AFB was associated with the risk of MetS in an N-shaped curve in women. In addition, women with high live births have a higher incidence of MetS.

A new lithophytic species, Paraboea zunyiensis T.Deng, F.Wen & R.B.Zhang (Gesneriaceae), inhabiting Karst rocks in northern Guizhou, China, is introduced and depicted in this study. It bears a resemblance to P. crassifolia (Hemsl.) B.L. Burtt, yet is distinguishable by its shorter filaments and staminodes, triangular ovate calyx segments, and ovaries surpassing the styles in length. Moreover, the phylogenetic tree constructed from nuclear DNA (ITS) and plastid DNA (trnL-F) data firmly support the differentiation of this novel species from P. crassifolia.

Abstract Background This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. Methods Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. Results A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P

Abstract Background The mechanism of hepatitis B virus (HBV)‐induced carcinogenesis remains an area of interest. The accumulation of hepatitis B surface antigen in the endoplasmic reticulum (ER) of hepatocytes stimulates persistent ER stress. Activity of the unfolded protein response (UPR) pathway of ER stress may play an important role in inflammatory cancer transformation. How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV‐related hepatocellular carcinoma (HCC) is still unclear. Here, we aimed to define the key molecule hyaluronan‐mediated motility receptor (HMMR) in this process and explore its role under ER stress in HCC development. Methods An HBV‐transgenic mouse model was used to characterize the pathological changes during the tumor progression. Proteomics and transcriptomics analyses were performed to identify the potential key molecule, screen the E3 ligase, and define the activation pathway. Quantitative real‐time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines. Luciferase reporter assay, chromatin immunoprecipitation, coimmunoprecipitation, immunoprecipitation, and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress. Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues. Results We found sustained activation of ER stress in the HBV‐transgenic mouse model of hepatitis‐fibrosis‐HCC. HMMR was transcribed by c/EBP homologous protein (CHOP) and degraded by tripartite motif containing 29 (TRIM29) after ubiquitination under ER stress, which caused the inconsistent expression of mRNA and protein. Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR. HMMR could alleviate ER stress by increasing autophagic lysosome activity. The negative correlation between HMMR and ER stress, positive correlation between HMMR and autophagy, and negative correlation between ER stress and autophagy were verified in human tissues. Conclusions This study identified the complicated role of HMMR in autophagy and ER stress, that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression, which could be a novel explanation for HBV‐related carcinogenesis.