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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.

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.

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

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.

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.

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.

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.

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 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.

Abstract Background Despite epidemiological evidence associating gallstone disease (GSD) with cardiovascular disease (CVD), a dilemma remains on the role of cholecystectomy in modifying the risk of CVD. We aimed to characterize the phenotypic and genetic relationships between GSD and two CVD events – stroke and coronary artery disease (CAD). Methods We first performed a meta-analysis of cohort studies to quantify an overall phenotypic association between GSD and CVD. We then investigated the genetic relationship leveraging the largest genome-wide genetic summary statistics. We finally examined the phenotypic association using the comprehensive data from UK Biobank (UKB). Results An overall significant effect of GSD on CVD was found in meta-analysis (relative risk [RR] = 1.26, 95% confidence interval [CI] = 1.19–1.34). Genetically, a positive shared genetic basis was observed for GSD with stroke ( $${r}_{g}$$ r g =0.16, P = 6.00 × 10–4) and CAD ( $${r}_{g}$$ r g =0.27, P = 2.27 × 10–15), corroborated by local signals. The shared genetic architecture was largely explained by the multiple pleiotropic loci identified in cross-phenotype association study and the shared gene-tissue pairs detected by transcriptome-wide association study, but not a causal relationship (GSD to CVD) examined through Mendelian randomization (MR) (GSD-stroke: odds ratio [OR] = 1.00, 95%CI = 0.97–1.03; GSD-CAD: OR = 1.01, 95%CI = 0.98–1.04). After a careful adjustment of confounders or considering lag time using UKB data, no significant phenotypic effect of GSD on CVD was detected (GSD-stroke: hazard ratio [HR] = 0.95, 95%CI = 0.83–1.09; GSD-CAD: HR = 0.98, 95%CI = 0.91–1.06), further supporting MR findings. Conclusions Our work demonstrates a phenotypic and genetic relationship between GSD and CVD, highlighting a shared biological mechanism rather than a direct causal effect. These findings may provide insight into clinical and public health applications.

Abstract The chromatin-based rule governing the selection and activation of replication origins in metazoans remains to be investigated. Here we report that NFIB, a member of Nuclear Factor I (NFI) family that was initially purified in host cells to promote adenoviral DNA replication but has since mainly been investigated in transcription regulation, is physically associated with the pre-replication complex (pre-RC) in mammalian cells. Genomic analyses reveal that NFIB facilitates the assembly of the pre-RC by increasing chromatin accessibility. Nucleosome binding and single-molecule magnetic tweezers shows that NFIB binds to and opens up nucleosomes. Transmission electron microscopy indicates that NFIB promotes nucleosome eviction on parental chromatin. NFIB deficiency leads to alterations of chromosome contacts/compartments in both G1 and S phase and affects the firing of a subset of origins at early-replication domains. Significantly, cancer-associated NFIB overexpression provokes gene duplication and genomic alterations recapitulating the genetic aberrance in clinical breast cancer and empowering cancer cells to dynamically evolve growth advantage and drug resistance. Together, these results point a role for NFIB in facilitating replication licensing by acting as a genome organizer, shedding new lights on the biological function of NFIB and on the replication origin selection in eukaryotes.

No novel biomarkers are currently available for evaluating immune reconstitution among people living with HIV/AIDS (PLWH) receiving combined antiretroviral treatment (cART). The objective of this study was to analyze the expression patterns of interferon-stimulating genes (ISGs) in PLWH with the aim of identifying potential biomarkers for immune reconstitution. Study samples were collected from 105 PLWH, including 47 immunological non-responders (INRs) and 58 immunological responders (IRs). The expression of eight ISGs in the peripheral blood in INRs and IRs were detected by RT-qPCR. Expression differences between groups were analyzed with the Mann-Whitney U test, and a logistic regression model was developed to predict immune reconstitution. Among eight ISGs, the expression levels of IFI27 and IFI6 were significantly higher in INRs than IRs ( P =0.001 and 0.005, respectively). The model combining age, CD4 + T/CD8 + T ratio, IFI27, and IFI6 had the highest diagnostic value (AUC=0.836), with an optimal cut-off value of 0.6, sensitivity of 60.5%, and specificity of 98.1%. No significant change in the expression of IFI27 and IFI6 was observed in samples collected 3 years apart ( P =0.1232 and 0.4877, respectively), and the model score negatively correlated with ΔCD4 + T cells (r=−0.2888, P =0.0465). Enhanced expression of IFI27 and IFI6 in INRs are important characteristics that may serve as biomarkers of immune reconstitution after cART. The combination of age, CD4 + T/CD8 + T ratio, IFI27, and IFI6 was highly effective in discriminating INRs.

The museum system is exposed to a high risk of seismic hazards. However, it is difficult to carry out seismic hazard prevention to protect cultural relics in collections due to the lack of real data and diverse types of seismic hazards. To address this problem, we developed a deep-learning-based multi-source feature-fusion method to assess the data on seismic damage caused by collected cultural relics. Firstly, a multi-source data-processing strategy was developed according to the needs of seismic impact analysis of the cultural relics in the collection, and a seismic event-ontology model of cultural relics was constructed. Additionally, a seismic damage data-classification acquisition method and empirical calculation model were designed. Secondly, we proposed a deep learning-based multi-source feature-fusion matching method for cultural relics. By constructing a damage state assessment model of cultural relics using superpixel map convolutional fusion and an automatic data-matching model, the quality and processing efficiency of seismic damage data of the cultural relics in the collection were improved. Finally, we formed a dataset oriented to the seismic damage risk analysis of the cultural relics in the collection. The experimental results show that the accuracy of this method reaches 93.6%, and the accuracy of cultural relics label matching is as high as 82.6% compared with many kinds of earthquake damage state assessment models. This method can provide more accurate and efficient data support, along with a scientific basis for subsequent research on the impact analysis of seismic damage to cultural relics in collections.

To investigate the effects of rapeseed diacylglycerol oil (RDG) intake on lipid accumulation and metabolism in C57BL/6J mice, obese mice were fed a high-fat diet in which 45% of the total energy content came from RDG (RDGM group) or rapeseed triacylglycerol oil (RTGM group). This diet intervention was conducted for 12 weeks following the establishment of the obese mouse model. By the end of the experiment, the serum glucose levels of the mice in the RTGM and RDGM groups were 13.0 ± 1.3 mmol/L and 9.7 ± 1.5 mmol/L, respectively. Meanwhile, the serum triglyceride level in the RDGM group was 26.3% lower than that in the RTGM group. The weight-loss effect in the RDGM group was accompanied by a significant decrease in the white adipose tissue (WAT) index. The RDG intervention did not significantly change the antioxidant and anti-inflammatory properties of the rapeseed oil in vivo. The RDG diet improved the liver lipid metabolism abnormalities induced by a high-fat diet, leading to decreased liver damage index values (AST and ALT). Additionally, compared to that in the RTGM group, the expression of the adipogenic genes PPAR-γ and DGAT decreased in both the liver and intestine by 21.7% and 16.7% and by 38.7% and 47.2%, respectively, in the RDGM group. Further, most lipolytic genes in BAT showed no significant change after the RDG intervention. This implies that RDG regulates lipid metabolism by altering the expression of adipogenic genes in the liver, intestine, and adipose tissue, thereby reducing the accumulation of WAT. Furthermore, the RDG diet enhanced gut flora diversity, increasing the relative levels of unclassified Muribaculaceae and decreasing the levels of Dubosiella and Faecalibaculum in the mouse gut, potentially accelerating lipid metabolism. Thus, a three-month RDG diet intervention in obese mice exhibited benefits in regulating the somatotype, serum obesity-related indices, gut flora structure, and lipid metabolism in the adipose tissue, liver, and intestine.

Considering the importance of calculating surface deformation based on monitoring data, this paper proposes a method for calculating horizontal deformation based on horizontal displacement monitoring data. This study first analyzes the characteristics of horizontal displacement monitoring data, then proposes a scheme for obtaining the surface horizontal displacement field through corresponding discrete point interpolation. Subsequently, the calculation method for surface horizontal strain is introduced, along with relevant examples. The study also systematically summarizes the calculation methods for surface curvature and surface tilt deformation values, forming a set of surface deformation calculation methods based on monitoring data. The research results indicate that when there is a large number of on-site monitoring points, effective monitoring points can be selected based on the direction of horizontal displacement. When interpolating the surface horizontal displacement field, the interpolation accuracy of the radial basis function method is slightly higher than that of ordinary Kriging. The form of coordinate expression has a significant impact on interpolation accuracy. The accuracy of interpolation using horizontal displacement vectors expressed in polar coordinates is higher than that using vectors expressed in Cartesian coordinates. The calculated surface horizontal strain has effective upper and lower limits, with lower-limit strain on the contour line conforming to the typical surface deformation patterns around mined-out areas.

Abstract Biogenesis of organelles requires targeting of a subset of proteins to specific subcellular domains by signal peptides or mechanisms controlling mRNA localization and local translation. How local distribution and translation of specific mRNAs for organelle biogenesis is achieved remains elusive and likely to be dependent on the cellular context. Here we identify Trinucleotide repeat containing-6a (Tnrc6a), a component of the miRNA pathway, distinctively localized to apical granules of differentiating airway multiciliated cells (MCCs) adjacent to centrioles. In spite of being enriched in TNRC6A and the miRNA-binding protein AGO2, they lack enzymes for mRNA degradation. Instead, we found these apical granules enriched in components of the mRNA translation machinery and newly synthesized proteins suggesting that they are specific hubs for target mRNA localization and local translation in MCCs. Consistent with this, Tnrc6a loss of function prevented formation of these granules and led to a broad reduction, rather than stabilization of miRNA targets. These included downregulation of key genes involved in ciliogenesis and was associated with defective multicilia formation both in vivo and in primary airway epithelial cultures. Similar analysis of Tnrc6a disruption in yolk sac showed stabilization of miRNA targets, highlighting the potential diversity of these mechanisms across organs.

The composite-laminated rotationally stiffened plate is widely applied in aviation, aerospace, ship, machinery, and other fields. For structural design and optimization, to investigate the vibration characteristics is important. In this paper, a modeling method of composite-laminated rotationally plate is established. The first-order shear deformation theory (FSDT) and the modified Fourier series are applied to construct the admissible displacement function of the stiffened plate-coupled systems. On this basis, the energy function of composite-laminated rotationally stiffened plate is established. Combined with the artificial virtual spring technology, the proposed theory could be used to analyze the vibration characteristics of composite-stiffened plate-coupled systems with various classical boundary conditions or arbitrary elastic boundary conditions. The Rayleigh–Ritz method is used to solve the energy function. Thus, the vibration characteristics of the composite-laminated rotationally stiffened plate are obtained and analyzed. The correctness of the theoretical analysis model was verified through modal experiments. On this basis, the effect of some important parameters on the vibration characteristics of stiffened plate structures is studied, such as the number, thickness, and width of the laminated stiffener, varying structural parameters, and different boundary conditions. This study can provide the theoretical basis for the vibration and noise reduction of such structures.