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Abstract Van der Waals integration of freestanding perovskite-oxide membranes with two-dimensional semiconductors has emerged as a promising strategy for developing high-performance electronics, such as field-effect transistors. In these innovative field-effect transistors, the oxide membranes have primarily functioned as dielectric layers, yet their great potential for structural tunability remains largely untapped. Free of epitaxial constraints by the substrate, these freestanding membranes exhibit remarkable structural tunability, providing a unique material system to achieve huge strain gradients and pronounced flexoelectric effects. Here, by harnessing the excellent structural tunability of PbTiO3 membranes and modulating the underlying substrate’s elasticity, we demonstrate the tip-pressure-induced polarization switching with an ultralow pressure (down to 0.06 GPa). Moreover, as an application demonstration, we develop a prototype non-volatile ferroelectric field-effect transistor integrated on silicon that can be operated mechanically and electrically. Our findings underscore the great potential of oxide membranes for utilization in advanced non-volatile electronics and highly sensitive pressure sensors.

Abstract Patients with spinal cord injury (SCI) have permanent devastating motor and sensory disabilities. Secondary SCI is known for its complex progression and presents with sophisticated aberrant inflammation, vascular changes, and secondary cellular dysfunction, which aggravate the primary damage. Since their initial discovery, the potent neuroprotective effects and powerful delivery abilities of exosomes (Exos) have been reported in different research fields, including SCI. In this study, we summarize therapeutic advances related to the application of Exos in preclinical animal studies. Subsequently, we discuss the mechanisms of action of Exos derived from diverse cell types, including neurogenesis, angiogenesis, blood–spinal cord barrier preservation, anti-apoptosis, and anti-inflammatory potential. We also evaluate the relationship between the Exo delivery cargo and signaling pathways. Finally, we discuss the challenges and advantages of using Exos to offer innovative insights regarding the development of efficient clinical strategies for SCI.

Abstract Diagnostic pathology, historically dependent on visual scrutiny by experts, is essential for disease detection. Advances in digital pathology and developments in computer vision technology have led to the application of artificial intelligence (AI) in this field. Despite these advancements, the variability in pathologists’ subjective interpretations of diagnostic criteria can lead to inconsistent outcomes. To meet the need for precision in cancer therapies, there is an increasing demand for accurate pathological diagnoses. Consequently, traditional diagnostic pathology is evolving towards “next-generation diagnostic pathology”, prioritizing on the development of a multi-dimensional, intelligent diagnostic approach. Using nonlinear optical effects arising from the interaction of light with biological tissues, multiphoton microscopy (MPM) enables high-resolution label-free imaging of multiple intrinsic components across various human pathological tissues. AI-empowered MPM further improves the accuracy and efficiency of diagnosis, holding promise for providing auxiliary pathology diagnostic methods based on multiphoton diagnostic criteria. In this review, we systematically outline the applications of MPM in pathological diagnosis across various human diseases, and summarize common multiphoton diagnostic features. Moreover, we examine the significant role of AI in enhancing multiphoton pathological diagnosis, including aspects such as image preprocessing, refined differential diagnosis, and the prognostication of outcomes. We also discuss the challenges and perspectives faced by the integration of MPM and AI, encompassing equipment, datasets, analytical models, and integration into the existing clinical pathways. Finally, the review explores the synergy between AI and label-free MPM to forge novel diagnostic frameworks, aiming to accelerate the adoption and implementation of intelligent multiphoton pathology systems in clinical settings.

Abstract Objective High low-density-lipoprotein (LDL) cholesterol has been associated with an increased risk of coronary artery diseases (CAD) including acute myocardial infarction (AMI). However, whether lipids lowering drug treatment is causally associated with decreased risk of AMI remains largely unknown. We used Mendelian randomization (MR) to evaluate the influence of genetic variation affecting the function of lipid-lowering drug targets on AMI. Methods Single-nucleotide polymorphisms (SNPs) associated with lipids as instruments were extracted from the Global Lipids Genetics Consortium (GLGC). The genome-wide association study (GWAS) data for AMI were obtained from UK Biobank. Two sample MR analysis was used to study the associations between high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) with AMI (n = 3,927). Genetic variants associated with LDL cholesterol at or near drug target gene were used to mimic drug effects on the AMI events in drug target MR. Results Genetically predicted higher LDL-C (per one SD increase in LDL-C of 38.67 mg/dL, OR 1.006, 95% CI 1.004–1.007) and TG (per one SD increase in TG of 90.72 mg/dL, 1.004, 1.002–1.006) was associated with increased risk of AMI, but decreased risk for higher HDL-C (per one SD increase in HDL-C of 15.51 mg/dL, 0.997, 0.995–0.999) in univariable MR. Association remained significant for LDL-C, but attenuated toward the null for HDL-C and TG in multivariable MR. Genetically proxied lower LDL-C with genetic variants at or near the PCSK9 region (drug target of evolocumab) and NPC1L1 (drug target of ezetimibe) were associated with decreased risk of AMI (0.997, 0.994–0.999 and 0.986, 0.975–0.998, respectively), whereas genetic variants at HMGCR region (drug target of statin) showed marginal association with AMI (0.995, 0.990-1.000). After excluding drug target-related SNPs, LDL-C related SNPs outside the drug target region remained a causal effect on AMI (0.994, 0.993–0.996). Conclusions The findings suggest that genetically predicted LDL-C may play a predominant role in the development of AMI. The drug MR results imply that ezetimibe and evolocumab may decrease the risk of AMI due to their LDL-C lowering effect, and there are other non-drug related lipid lowering pathways that may be causally linked to AMI.

Abstract The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.

Abstract Introduction Subjective cognitive decline (SCD) refers to individuals’ perceived decline in memory and/or other cognitive abilities relative to their previous level of performance. Sensory decline is one of the main manifestations of decline in older adults with SCD. The efficient integration of visual and auditory information, known as audiovisual integration, is a crucial perceptual process. This study aims to evaluate audiovisual integration in older adults with SCD. Methods We adopted the audiovisual detection task, the Colavita task, and the Sound‐Induced Flash Illusion (SIFI) task to evaluate the audiovisual integration by examining both redundant and illusory effects. Older adults diagnosed with SCD (N = 50, mean age = 67.8 years) and a control group of non‐SCD older adults (N = 51, mean age = 66.5 years) were recruited. All participants took part in the three aforementioned experiments. Results The outcomes showed that a redundant effect occurred in both SCD and non‐SCD older adults, with SCD older adults gaining more benefits in audiovisual detection task. Moreover, an equivalent amount of the visual dominance effect was observed among both SCD and non‐SCD older adults in Colavita task. In addition, older adults with SCD perceived an equal fission illusion but a bigger fusion illusion compared with non‐SCD older adults in SIFI task. Conclusions Overall, older adults with SCD exhibit increased audiovisual redundant effects and stronger fusion illusion susceptibility compared to non‐SCD older adults. Besides, visual dominance was observed in both groups via the Colavita task, with no significant difference between non‐SCD and SCD older adults. These findings implied that audiovisual integration might offer a potential way for the identification of SCD.

Abstract Background Hepatoid adenocarcinoma (HAC) is rare in the urinary system, with only 7 reported cases in upper urinary tract. This report aimed to explore the genetic characteristics of ureteral HAC for first time, and to describe the treatment prognosis of ureteral HAC. Case presentation We present a rare case of ureteral HAC in a 53-year-old female, showing elevated serum levels of AFP and CEA, prolonged chronic irritation may be an important cause of her ureteral HAC. Radical nephroureterectomy was performed, the serum levels of AFP and CEA decreased significantly, and metastasis in lymph nodes was found at 9 months after surgery, she had no related symptoms after 18 months postoperatively without adjuvant chemotherapy. Three driver somatic mutations in cancer were identified by NGS testing, including: TP53D281H, KMT2DL1211Ifs*2, KMT2DT1843Nfs*5, demonstrating that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma. Homologous-recombination deficiency (HRD) was positive in this tumor with no mutations in HRD-related genes, which was possibly induced by the copy number deletion of SETD2 gene. Conclusions We report a rare case of ureteral HAC with elevated serum levels of AFP and CEA. NGS testing demonstrated that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma, which is an important guide for the diagnosis and treatment of ureteral HAC.

Abstract Background Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery. Results The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI. Conclusions These results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.

Abstract Background Maintaining the repair phenotype of denervated Schwann cells in the injured distal nerve is crucial for promoting peripheral nerve regeneration. However, when chronically denervated, the capacity of Schwann cells to support repair and regeneration deteriorates, leading to peripheral nerve regeneration and poor functional recovery. Herein, we investigated whether neurotrophin-3 (NT-3) could sustain the reparative phenotype of Schwann cells and promote peripheral nerve regeneration after chronic denervation and aimed to uncover its potential molecular mechanisms. Methods Western blot was employed to investigate the relationship between the expression of c-Jun and the reparative phenotype of Schwann cells. The inducible expression of c-Jun by NT-3 was examined both in vitro and in vivo with western blot and immunofluorescence staining. A chronic denervation model was established to study the role of NT-3 in peripheral nerve regeneration. The number of regenerated distal axons, myelination of regenerated axons, reinnervation of neuromuscular junctions, and muscle fiber diameters of target muscles were used to evaluate peripheral nerve regeneration by immunofluorescence staining, transmission electron microscopy (TEM), and hematoxylin and eosin (H&E) staining. Adeno-associated virus (AAV) 2/9 carrying shRNA, small molecule inhibitors, and siRNA were employed to investigate whether NT-3 could signal through the TrkC/ERK pathway to maintain c-Jun expression and promote peripheral nerve regeneration after chronic denervation. Results After peripheral nerve injury, c-Jun expression progressively increased until week 5 and then began to decrease in the distal nerve following denervation. NT-3 upregulated the expression of c-Jun in denervated Schwann cells, both in vitro and in vivo. NT-3 promoted peripheral nerve regeneration after chronic denervation, mainly by upregulating or maintaining a high level of c-Jun rather than NT-3 itself. The TrkC receptor was consistently presented on denervated Schwann cells and served as NT-3 receptors following chronic denervation. NT-3 mainly upregulated c-Jun through the TrkC/ERK pathway. Conclusion NT-3 promotes peripheral nerve regeneration by maintaining the repair phenotype of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway. It provides a potential target for the clinical treatment of peripheral nerve injury after chronic denervation.

Abstract Stitched fluorescence microscope images inevitably exist in various types of stripes or artifacts caused by uncertain factors such as optical devices or specimens, which severely affects the image quality and downstream quantitative analysis. Here, we present a deep learning-based Stripe Self-Correction method, so-called SSCOR. Specifically, we propose a proximity sampling scheme and adversarial reciprocal self-training paradigm that enable SSCOR to utilize stripe-free patches sampled from the stitched microscope image itself to correct their adjacent stripe patches. Comparing to off-the-shelf approaches, SSCOR can not only adaptively correct non-uniform, oblique, and grid stripes, but also remove scanning, bubble, and out-of-focus artifacts, achieving the state-of-the-art performance across different imaging conditions and modalities. Moreover, SSCOR does not require any physical parameter estimation, patch-wise manual annotation, or raw stitched information in the correction process. This provides an intelligent prior-free image restoration solution for microscopists or even microscope companies, thus ensuring more precise biomedical applications for researchers.

As a promising cathode material, olivine-structured LiMnPO4 holds enormous potential for lithium-ion batteries. Herein, we demonstrate a green biomass-derived phytic-acid-assisted method to synthesize a series of LiMn1−xFexPO4/C composites. The effect of Fe doping on the crystal structure and morphology of LiMnPO4 particles is investigated. It is revealed that the optimal Fe doping amount of x = 0.2 enables a substantial enhancement of interfacial charge transfer ability and Li+ ion diffusion kinetics. Consequently, a large reversible capacity output of 146 mAh g−1 at 0.05 C and a high rate capacity of 77 mAh g−1 at 2 C were acquired by the as-optimized LiMn0.8Fe0.2PO4/C cathode. Moreover, the LiMn0.8Fe0.2PO4/C delivered a specific capacity of 68 mAh g−1 at 2 C after 500 cycles, with a capacity retention of 88.4%. This work will unveil a green synthesis route for advancing phosphate cathode materials toward practical implementation.

The Haihe Plain in China is situated in the world’s largest groundwater funnel area, with per capita water resources far below the internationally recognized “extremely water-scarce” standard. To address the issue of water shortage in summer maize-planting areas of the Haihe Plain, we conducted research on the variation of summer maize evapotranspiration using a medium-sized lysimeter. This study aims to provide technical support for water-saving irrigation in summer maize fields. Through path analysis, direct and indirect influencing factors affecting the evapotranspiration of summer maize fields were determined. The results showed that the cumulative evapotranspiration of bare ground and farmland during the entire growth period of summer maize was 173.57 mm and 382.97 mm, respectively, with evapotranspiration intensities of 1.52 mm/d and 3.36 mm/d, respectively. Evapotranspiration during the maturity stage of summer maize was the least, accounting for only 1.82% of total evapotranspiration during the entire growth period. The period from the jointing to milk-ripening stage is when evapotranspiration in maize fields is at its highest. During this period, evapotranspiration in maize fields amounted to 265.58 mm, accounting for 69.35% of total evapotranspiration. The evapotranspiration intensity was 3.59 mm/day, which is 1.34 times higher than that of bare soil. The evapotranspiration intensities during each growth stage were ranked as jointing stage > tasseling-silking stage > seedling stage > milk maturity stage > maturity stage. The daily evapotranspiration of summer maize fields showed a “unimodal” curve with low values in the morning and evening, and high values at noon. Path analysis indicated that daily radiation and maximum daily temperature had the greatest impact on the evapotranspiration of maize fields, with the direct effect of maximum daily temperature being restrictive and the indirect effect being promotive, resulting in an overall promotive effect.

Objective: To compare the effects of oral intake and nasogastric tube (NG) feeding on nutritional status, complications and survival during neoadjuvant chemoradiotherapy for esophageal squamous-cell carcinoma (ESCC) patients. Methods: A total of 61 ​ESCC cases treated with neoadjuvant chemoradiotherapy from December 2018 to March 2020 were enrolled, including (38 in oral intake group, and 22 in NG feeding group. Disease characteristics and baseline nutritional markers were collected in both groups. Nutritional status, complication and completion rate of chemoradiotherapy in both groups were evaluated. Results: Compared with the oral intake group, patients in the NG feeding group had a later T stage (P ​= ​0.027) and clinical stage (P ​= ​0.014). The levels of energy intake (P ​= ​0.033), serum prealbumin (P ​ ​0.05). Conclusions: As a safe and effective enteral nutrition approach to improving nutrition, nasogastric tube feeding could increase treatment completion rate and reduce the incidence of ≥ grade 2 esophagitis reaction during neoadjuvant chemoradiotherapy.

Abstract Background and Aims The occurrence, growth, and metastasis of colorectal cancer (CRC) are connected to the hypercoagulable state of blood (CRC). This study aimed to identify significant coagulation factors to predict metastasis and prognosis of CRC. Methods Thrombomodulin (TM), thrombin‐antithrombin complex (TAT), α2‐plasmininhibitor‐plasmin complex (PIC), and tissue plasminogen activator‐inhibitor complex (t‐PAIC) were detected by chemiluminescence immunoassay using Sysmex HISCL5000 automated analyzers. The Sysmex CS 5100 automatic blood coagulation analyzer was used to detect d‐dimer (DD), fibrin degradation product (FDP), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fbg), and activated partial thromboplastin time (APTT). Area under the curve (AUC) and the receiver operating characteristic curve (ROC) were used to assess the diagnostic efficacy of markers. Kaplan–Meier analysis was used to calculate survival probabilities. Independent prognostic factors and the nomogram were developed using single‐factor and multifactor cox regression analysis model. Results The following indicators (TM, TAT, PIC, t‐PAIC, DD, FDP, PT, INR, APTT, and Fbg) were markedly higher in CRC patients than in healthy controls, and they were higher in the metastasis (M) group than in the nonmetastasis (NM) group. The combination “TAT + PIC + DD + FDP + Fbg” can distinguish M from NM with exceptional sensitivity and specificity. Patients with CRC who had high levels of TAT, PIC, DD, FDP, Fbg, TM, tPAIC, PT, and INR had significantly shorter survival. Conclusion The prognosis of CRC patients can be predicted by coagulation indicators. The independent predictive variables for overall survival were found to be TM and DD. To forecast CRC patient survival, a nomogram was created.

Promoting the recovery of neurological function in patients with traumatic spinal cord injury (TSCI) remains challenging. The balance between astrocyte-mediated neurotrophic and pro-inflammatory responses is critical for TSCI repair. Recently, the utilization of nanomaterials has been considerably explored in immunological reconstructive techniques that specifically target astrocyte-mediated inflammation, yielding positive outcomes. In this review, we aim to condense the present knowledge regarding the astrocyte-mediated inflammation following TSCI. We then review the various categories of nanomaterials utilized in the management of astrocyte-mediated inflammation in TSCI and conclude by summarizing their functions and advantages to offer novel insights for the advancement of effective clinical strategies targeting TSCI.

Abstract Background Narrow host range is a major limitation for phage applications, but phages can evolve expanded host range through adaptations in the receptor-binding proteins. Results Here, we report that Pseudomonas phage K8 can evolve broader host range and higher killing efficiency at the cost of virion stability. Phage K8 host range mutant K8-T239A carries a mutant version of the putative baseplate wedge protein GP075, termed GP075m. While phage K8 adsorbs to hosts via the O-specific antigen of bacterial LPS, phage K8-T239A uses GP075m to also bind the bacterial core oligosaccharide, enabling infection of bacterial strains resistant to K8 infection due to modified O-specific antigens. This mutation in GP075 also alters inter-protein interactions among phage proteins, and reduces the stability of phage particles to environmental stressors like heat, acidity, and alkalinity. We find that a variety of mutations in gp075 are widespread in K8 populations, and that the gp075-like genes are widely distributed among the domains of life. Conclusion Our data show that a typical life history tradeoff occurs between the stability and the host range in the evolution of phage K8. Reservoirs of viral gene variants may be widely present in phage communities, allowing phages to rapidly adapt to any emerging environmental stressors. Video Abstract

Abstract Background Salt-alkali stress represents one of the most stressful events with deleterious consequences for plant growth and crop productivity. Despite studies focusing on the effects of salt-alkali stress on morphology and physiology, its molecular mechanisms remain unclear. Here, we employed RNA-sequencing (RNA-seq) to understand how Na2CO3 stress inhibits rice seedling growth. Results Na2CO3 stress significantly inhibited the growth of rice seedlings. Through RNA-seq, many differentially expressed genes (DEGs) were shown to be potentially involved in the rice seedling response to salt-alkali stress. After 1-day and 5-day treatments, RNA-seq identified 1780 and 2315 DEGs in the Na2CO3-treated versus -untreated rice seedling shoots, respectively. According to the gene ontology enrichment and the Kyoto Encylopedia of Genes and Genomes annotation of DEGs, the growth-inhibition processes associated with salt-alkali stress involve a myriad of molecular events, including biosynthesis and metabolism, enzyme activity, and binding, etc. Conclusion Collectively, the transcriptome analyses in the present work revealed several potential key regulators of plant response to salt-alkali stress, and might pave a way to improve salt-alkali stress tolerance in rice.

Abstract Background The fat‐to‐muscle mass ratio (FMR), which integrates the antagonistic effects of fat and muscle mass, has been proposed as a useful indicator to assess disease risk independent of overall obesity. However, little is known about the association between FMR and dementia risk. We aimed to prospectively investigate the sex‐specific associations between total and regional FMR and incident dementia. Methods A total of 491 420 participants (223 581 men and 267 839 women; mean age 56.7 ± 8.2 and 56.3 ± 8.0 years old, respectively) free of dementia at baseline from the UK Biobank were included. Fat mass and muscle mass were measured using a bioelectrical impedance assessment device. Cox regression analyses were used to examine the associations of total and regional FMR with incident all‐cause dementia, Alzheimer's disease (AD) and vascular dementia (VD). The shape of the associations of the continuous scale of FMR and incident dementia were examined using restricted cubic spline analysis. Results During a median 8.65 years of follow‐up, we documented 2 225 incident all‐cause dementia cases, including 836 AD and 468 VD cases. There was an L‐shaped association between whole body FMR and all‐cause dementia risk in both sexes after adjusting body mass index (BMI) and other covariates (P for non‐linear

With the increasing demand for application development of task publishers (e.g., automobile enterprises) in the Internet of Vehicles (IoV), federated learning (FL) can be used to enable vehicle users (VUs) to conduct local application training without disclosing data. However, the challenges of VUs’ intermittent connectivity, low proactivity, and limited resources are inevitable issues in the process of FL. In this paper, we propose a UAV-assisted FL framework in the context of the IoV. An incentive stage and a training stage are involved in this framework. UAVs serve as central servers, which assist to incentivize VUs, manage VUs’ contributed resources, and provide model aggregation, making sure communication efficiency and mobility enhancement in FL. The numerical results show that, compared with the baseline algorithms, the proposed algorithm reduces energy consumption by 50.3% and improves model convergence speed by 30.6%.

Prussian blue analogs (PBAs) are effective precatalysts for the oxygen evolution reaction (OER); however, the underlying mechanism of their electrochemical activation is still not well elucidated. In this study, we designed and constructed PBA-based precatalysts to determine the electrochemical activation mechanism and achieve high-efficiency OER. The PBAs undergo in situ electrochemical transformation to form the corresponding metal (oxy)hydroxides (M(O)OH) as the true OER catalyst. More importantly, the hexacyanoferrate ligands undergo repetitive interfacial coordination/etching with/from M(O)OH during the activation process. The distinct mechanism could achieve in situ Fe doping and enable defect incorporation. The defect-enriched Fe-NiOOH derived from a well-designed NiHCF/Ni(OH)2 precatalyst requires a low overpotential of 227 mV to reach a current density of 10 mA cm−2 and works stably at 130 mA cm−2 over 100 h. This study provides fundamental insights into the electrochemical activation mechanism for developing advanced precatalysts for OER.

Objective: To study phage applications in the control of bacteria contaminations, Pseudomonas aeruginosa phage K4 was characterized for its biological characteristics and inhibition effects of bacterial growth. Methods: One-step growth curve, phage stability, genome sequencing, comparative genomics analysis, and growth inhibition curve were conducted in this work. Results: One-step growth curve showed that phage K4 had a latent phase of 15 min and a burst size of about 85 PFU/infection center, displaying a strong infectivity. Under different MOIs (multiplicity of infection), phage K4 efficiently inhibited the growth of the host cells. Genomic analysis revealed that phage K4 had a genome of 50358 bp with 77 coding sequences and 1 tRNA-Arg gene. Comparative genomics showed that the genome of phage K4 shared an identity of 95.08% with Pseudomonas virus PA11 which belongs to the Paundecimvirus genus of the Zobellviridae family, suggesting that phage K4 might be a new member of the Paundecimvirus genus. In application assays, phage K4 could significantly control the growth of the host cells in sterilized milk and ready-to-eat beef samples along with obvious reproductions of phage K4. In conclusion, the data suggested that phage K4 was a lytic virus that replicated rapidly with relatively high bactericidal activity. Conclusion: The genome of phage K4 did not carry genes for integration, antibiotic resistance, and virulence, appropriately to be selected as a biocontrol agent in the control and prevention of P. aeruginosa contaminations in foods.

Abstract Background Both extracellular vesicles from mesenchymal stromal cell-derived human umbilical cords (hUC-EVs) and arsenic trioxides (ATOs) have been demonstrated to treat acute graft-versus-host disease (aGVHD) via immunomodulation. Apart from immunomodulation, hUC-EVs have a unique function of drug delivery, which has been proposed to enhance their efficacy. In this study, we first prepared ATO-loaded hUC-EVs (hUC-EVs-ATO) to investigate the therapeutic effect and potential mechanisms of hUC-EVs-ATO in a mouse model of aGVHD after allogeneic hematopoietic stem cell transplantation (HSCT). Methods An aGVHD model was established to observe the therapeutic effects of hUC-EVs-ATO on aGVHD. Target organs were harvested for histopathological analysis on day 14 after transplantation. The effects of hUC-EVs-ATO on alloreactive CD4+ were evaluated by flow cytometry in vivo and in vitro. Flow cytometry, RT-PCR, immunofluorescence colocalization analysis and Western blot (Wb) analysis were performed to examine macrophage polarization after hUC-EV-ATO treatment. The cytokines in serum were measured by a cytometric bead array (CBA). TEM, confocal microscopy and Wb were performed to observe the level of autophagy in macrophages. A graft-versus-lymphoma (GVL) mouse model was established to observe the role of hUC-EVs-ATO in the GVL effect. Results The clinical manifestations and histological scores of aGVHD in the hUC-EVs-ATO group were significantly reduced compared with those in the ATO and hUC-EVs groups. The mice receiving hUC-EVs-ATO lived longer than the control mice. Notably, hUC-EVs-ATO interfering with alloreactive CD4+ T cells differentiation were observed in aGVHD mice but not in an in vitro culture system. Additional studies showed that depletion of macrophages blocked the therapeutic effects of hUC-EVs-ATO on aGVHD. Mechanistically, hUC-EVs-ATO induced autophagic flux by inhibiting mammalian target of rapamycin (mTOR) activity to repolarize M1 to M2 macrophages. Additionally, using a murine model of GVL effects, hUC-EVs-ATO were found not only to reduce the severity of aGVHD but also to preserve the GVL effects. Taken together, hUC-EVs-ATO may be promising candidates for aGVHD treatment. Conclusions hUC-EVs-ATO enhanced the alleviation of aGVHD severity in mice compared with ATO and hUC-EVs without weakening GVL activity. hUC-EVs-ATO promoted M1 to M2 polarization via the mTOR-autophagy pathway. hUC-EVs-ATO could be a potential therapeutic approach in aGVHD after allo-HSCT.

Abstract Hemophagocytic lymphohistiocytosis (HLH), particularly primary HLH (pHLH), is a rare, life-threatening disease. Germline genetic deficiency of 12 known HLH genes impairs cytotoxic degranulation in natural killer (NK) cells or cytotoxic T lymphocytes (CTLs) and contributes to pHLH development. However, no pathogenic mutations in these HLH genes are found in nearly 10% of HLH patients, despite a strong suspicion of pHLH, suggesting that the underlying genetic basis of HLH is still unclear. To discover novel susceptibility genes, we first selected 13 children with ppHLH (presumed primary HLH patients in the absence of detectable known HLH gene variants) and their parents for initial screening. Whole-genome sequencing (WGS) in one trio and whole-exome sequencing (WES) in twelve trios revealed that two ppHLH patients carried biallelic NBAS variants, a gene that is involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport upstream of the degranulation pathway. Additionally, two candidate genes, RAB9B and KLC3, showed a direct relationship with known HLH genes in protein-protein interaction (PPI) network analysis. We analyzed NBAS, RAB9B, KLC3 and known HLH genes in an independent validation cohort of 224 pediatric HLH patients. Only biallelic NBAS variants were identified in three patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-deficient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus. According to our findings, NBAS is the second most frequently mutated gene (2.11%) in our HLH cohort after PRF1. NBAS deficiency may contribute to the development of HLH via a dysregulated lytic vesicle transport pathway.

Background The evidence is equivocal on the association between meat consumption and ischemic heart disease (IHD) risk. To what extent the variation of individuals' metabolic responses to the same diet may account for this association is not fully understood. We aim to identify metabolomic signatures characterizing consumption of unprocessed red meat and processed meat and whether such signatures are associated with IHD risk. Methods and Results We conducted a cohort study of 92 246 individuals (mean age, 56.1 years; 55.1% women) using the UK Biobank. During the median follow‐up of 8.74 years, 3059 incident IHD events were documented. Unprocessed red meat and processed meat consumption was assessed using a touchscreen dietary questionnaire. Plasma metabolome was profiled by high‐throughput nuclear magnetic resonance spectroscopy. Cox proportional hazards regression model was used to test the association of meat consumption with IHD. Genome‐wide association analysis and 1‐sample Mendelian randomization were performed for metabolomic signatures and causal association of signatures with IHD. Using elastic net regularized regressions, we constructed metabolomic signatures consisting of 157 and 142 metabolites for unprocessed red meat (Spearman correlation coefficient [r]=0.223) and processed meat (r=0.329), respectively. These signatures showed positive associations with incident IHD (red meat related signature: hazard ratio [HR] per SD increment=1.11 [95% CI, 1.06–1.16], P

Background The Healthy Aging Index (HAI) has been regarded as useful in capturing the health status of multiple organ systems. However, to what extent the HAI is associated with major cardiovascular events remains largely unknown. The authors constructed a modified HAI (mHAI) to quantify the association of physiological aging with major vascular events and explored how the effects of a healthy lifestyle can modify this association. Methods and Results The participants with either missing values of any individual mHAI component or major illnesses such as heart attack, angina and stroke, and self‐reported cancer at baseline were excluded. The mHAI components include systolic blood pressure, reaction time, forced vital capacity, serum cystatin c, and serum glucose. The authors used Cox proportional hazard models to quantify the association of mHAI with major adverse cardiac events, major coronary events, and ischemic heart disease. Cumulative incidence at 5 and 10 years was estimated, and joint analyses were stratified by age group and 4 mHAI categories. The mHAI was significantly correlated with major cardiovascular events, which is a better reflection of the aging level of the body than chronological age. An mHAI was calculated in 338 044 participants aged 38 to 73 years in the UK Biobank. Each point increase in the mHAI was associated with a 44% higher risk of major adverse cardiac events (adjusted hazard ratio [aHR], 1.44 [95% CI, 1.40–1.49]), 44% higher risk of major coronary events (aHR, 1.44 [95% CI, 1.40–1.48]), and 36% higher risk of ischemic heart disease (aHR, 1.36 [95% CI, 1.33–1.39]). The percentage of population‐attribution risk was 51% (95% CI, 47–55) for major adverse cardiac events, 49% (95% CI, 45–53) for major coronary events, and 47% (95% CI, 44–50) for ischemic heart disease, which means that a substantial portion of these events could be prevented. Systolic blood pressure was the factor most significantly associated with major adverse cardiac events (aHR, 1.94 [95% CI, 1.82–2.08]; percentage of population‐attribution risk, 36%), major coronary events (aHR, 2.01 [95% CI, 1.85–2.17]; percentage of population‐attribution risk, 38%), and ischemic heart disease (aHR, 1.80 [95% CI, 1.71–1.89]; percentage of population‐attribution risk, 32%). A healthy lifestyle significantly attenuated mHAI associations with incidence of vascular events. Conclusions Our findings indicate that higher mHAI is associated with increased major vascular events. A healthy lifestyle may attenuate these associations.

Ex vivo-expanded mesenchymal stem cells (MSCs) have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative, multipotential, and immunomodulatory capacities. However, the exact characteristics of MSCs remain largely unknown. By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton’s jelly, we revealed five distinct subpopulations. The developmental trajectory of these five MSC subpopulations was mapped, revealing a differentiation path from stem-like active proliferative cells (APCs) to multipotent progenitor cells, followed by branching into two paths: 1) unipotent preadipocytes or 2) bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondrocytes. The stem-like APCs, expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES, uniquely exhibited strong proliferation and stemness signatures. Remarkably, the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3+ T cell proliferation in vitro, supporting the role of this population in immunoregulation. In summary, our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation. Our findings advance the definition of MSCs by identifying the specific functions of their heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of their functional subpopulations.

Rice seedlings were exposed to two CO2 concentrations (400 ± 20 and 800 ± 20 μmol mol−1) and three PbNO3 concentrations (0, 50 and 100 µmol L−1) for 10 days to explore the regulatory mechanisms of elevated CO2 for Pb stress resistance. Electrical conductivity, MDA content, SOD, POD, CAT activities and metabolomics changes were studied. Results showed that: Pb stress damaged cell membrane system, electrical conductivity and MDA content increased 49.34 % and 73.27 %, respectively, and some antioxidant enzymes activities increased. Sugar, polyol, amino acid metabolism and fatty acid β-oxidation were all enhanced to improve osmotic adjustments, maintain cell membrane stability, supply energy, nitrogen assimilates and antioxidant capacity; Under composite treatments, cell membrane damage was reduced, activities of protective enzymes increased compared with only Pb stress, POD activity increased the most (49.14 %) under severe Pb composite treatment. High CO2 caused the enhance of cells antioxidant capacity, TCA cycle intermediate products contents and fatty acid desaturation under mild Pb stress. Many sugars, polyols and amino acids contents were increased as osmotic regulatory substances by high CO2 under severe Pb stress; Secondary metabolites played an important role under Pb stress and composite treatments. The object of this study is to provide a possible molecular mechanism of rice response to Pb stress under high CO2 in the future.

To address the problems of low prediction accuracy and slow convergence of the network security posture prediction model, a population intelligence optimization algorithm is proposed to improve the network security posture prediction model of the BP neural network. First, the adaptive adjustment of the two parameters with the increase of iterations is achieved by improving the inertia weights and learning factors in the particle swarm optimization (PSO) algorithm so that the PSO has a large search range and high speed at the initial stage and a strong and stable convergence capability at the later stage. Secondly, to address the problem that PSO is prone to fall into a local optimum, the genetic operator is embedded into the operation process of the particle swarm algorithm, and the excellent global optimization performance of the genetic algorithm is used to open up the spatial vision of the particle population, revive the stagnant particles, accelerate the update amplitude of the algorithm, and achieve the purpose of improving the premature problem. Finally, the improved algorithm is combined with the BP neural network to optimize the BP neural network and applied to the network security posture assessment. The experimental comparison of different optimization algorithms is applied, and the results show that the network security posture prediction method of this model has the smallest error, the highest accuracy, and the fastest convergence, and can effectively predict future changes in network security posture.

Abstract Background Clear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy. Methods Bioinformatics analysis of The Cancer Genome Atlas (TCGA), the NCBI Gene Expression Omnibus (GEO) database, USUC Xena database, cBioPortal for Cancer Genomics, and MethSurv were performed to examine the aberrant genetic pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression. The regulation of ccRCC tumor cell lines proliferation by LRRK2 was examined by CCK8 assay. Results Bioinformatics analysis showed that LRRK2 expression was up-regulated and largely correlated with DNA methylation in ccRCC. The up-regulation of LRRK2 was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage, and metastatic status of ccRCC patients. Meanwhile, Kaplan–Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; knockdown of LRRK2 expression attenuated the proliferation ability of ccRCC tumor cell lines; protein–protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR. Conclusion We found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC.

A kinase anchor protein 12（AKAP12）is a scaffold protein that is critical for cell structure maintenance and signal transduction. However, the role of AKAP12 in liver injury remains unclear. Here, we attempt to explore the potential contribution of AKAP12 in liver injury and elucidate its underlying molecular mechanism. We found that AKAP12 deletion in acute liver injury (ALI) activates the PI3K/AKT phosphorylation signaling pathway, induces the increased expression of PCSK6 and its downstream inflammation-related genes, and prompts macrophages to produce a large number of inflammatory factors. And knockdown of PCSK6 by in vivo siRNA assay reversed in liver injury AKAP12Δhep mice, demonstrating that PCSK6 has an important role in ALI. Furthermore, we found that signal transducer and activator of transcription 3 (STAT3) and serine/threonine kinase Akt (AKT) were upregulated in AKAP12Δhep mice of chronic liver injury. To sum up, our study here demonstrates that AKAP12 has a protective role in ALI and chronic liver fibrosis, at least in part through inhibition of the PI3K/AKT/PCSK6 pathway. Our findings provide a new potential treatment for liver injury with important clinical implications.

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with a poor prognosis. We aimed to identify a new prognostic model of HCC based on differentially expressed (DE) immune genes. Methods The DE immune genes were identified based on an analysis of 374 cases of HCC and 50 adjacent non-tumor specimens from the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis, Lasso regression, and multivariate Cox analysis were used to construct the model based on the training group. Survival analysis and the receiver operating characteristic (ROC) curves were used to evaluate model performance. The testing group and the entire group were subsequently used for validation of the model. Results A five-immune gene model consisted of HSPA4, ISG20L2, NDRG1, EGF, and IL17D was identified. Based on the model, the overall survival was significantly different between the high-risk and low-risk groups (P = 7.953e-06). The AUCs for the model at 1- and 3-year were 0.849 and 0.74, respectively. The reliability of the model was confirmed using the validation groups. The risk score was identified as an independent prognostic parameter and closely related to the content of immune cells from human HCC specimens. Conclusion We identified a five-immune gene model that can be used as an independent prognostic marker for HCC.

Abstract Two subspecies of rice, Oryza sativa ssp. indica and O. sativa ssp. japonica, with reproductive isolation and differences in morphology and phenotypic differences, were established during the process of rice domestication. To understand how domestication has changed the transcriptomes of the two rice subspecies and given rise to the phenotypic differences, we obtained approximately 700 Gb RNA-Seq data from 26 indica and 25 japonica accessions, and identified 97,005 transcribed fragments and 4579 novel transcriptionally active regions. The two rice subspecies had significantly different gene expression profiles, we identified 1,357 (3.3% in all genes) differentially expressed genes (DEGs) between indica and japonica rice. Combining existing gene function studies, it is found that some of these differential genes are related to the differentiation of the two subspecies, such as grain shape and cold tolerance, etc. Functional annotation of these DEGs indicates that they are involved in cell wall biosynthesis and reproductive processes. Furthermore, compared with the non-DEGs, the DEGs from both subspecies had more 5′flanking regions with low polymorphism to divergence ratios, indicating a stronger positive selection pressure on the regulation of the DEGs. This study improves our understanding of the rice genome by comparatively analyzing the transcriptomes of indica and japonica rice and identifies DEGs those may be responsible for the reproductive isolation and phenotypic differences between the two rice subspecies.

Introduction Protein kinase A (PKA) and protein kinase G (PKG) are the main downstream effectors of second messengers cAMP and cGMP, which play important roles in physiological and pathological processes. Recently, there are two findings: one is PKA catalytic subunits α (PKACα) and PKG II can be secreted, the other is that the two secretory protein kinases are associated with the progression of tumors. Previous data also demonstrate that the two kinases, as signal cascades, involved in inflammation-associated disorders. However, it remains unclear whether the secreted PKACα or PKG II could serve as diagnostic biomarkers for inflammation-associated disorders. Methods The serum from suffered coronary disease, diabetes, rheumatoid arthritis, and schizophrenia were collected. The serum PKACα and PKG II were detected by ELISA. All the patients were consent informed. Results Our results showed that the serum PKACα and PKG II had obvious changes in coronary disease, rheumatoid arthritis, schizophrenia patients. However, the trends was opposite, especially in rheumatoid arthritis. Conclusions Serum PKACα and PKG II could serve as potentially diagnostic biomarkers for some inflammation-associated disorders, such as coronary disease, rheumatoid arthritis, and schizophrenia.

The recent observation of superconductivity in nickelate thin films has attracted a lot of attentions. Here, authors report single particle tunneling spectra on the superconducting nickelate thin films revealing two types of gap feature with one V-shape and the other a full gap.

Abstract Background Endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) both have advantages and disadvantages for the treatment of carpal tunnel syndrome (CTS). We compared the effectiveness and safety of ECTR and OCTR based on evidence from a high-level randomized controlled trial. Methods We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Medline to identify relevant articles published until August 2019. Data regarding operative time, grip strength, Boston Carpal Tunnel Questionnaire scores, digital sensation, patient satisfaction, key pinch strength, return to work time, and complications were extracted and compared. All mean differences (MD) and odds ratios (OR) were expressed as ECTR relative to OCTR. Results Our meta-analysis contained twenty-eight studies. ECTR was associated with significantly higher satisfaction rates (MD, 3.13; 95% confidence interval [CI], 1.43 to 4.82; P = 0.0003), greater key pinch strengths (MD, 0.79 kg; 95% CI, 0.27 to 1.32; P = 0.003), earlier return to work times (MD, − 7.25 days; 95% CI, − 14.31 to − 0.19; P = 0.04), higher transient nerve injury rates (OR, 4.87; 95% CI, 1.37 to 17.25; P = 0.01), and a lower incidence of scar-related complications (OR, 0.20; 95% CI, 0.07 to 0.59; P = 0.004). The permanent nerve injury showed no significant differences between the two methods (OR, 1.93; 95% CI, 0.58 to 6.40; P = 0.28). Conclusions Overall, evidence from randomized controlled trials indicates that ECTR results in better recovery of daily life functions compared to OCTR, as revealed by higher satisfaction rates, greater key pinch strengths, earlier return to work times, and fewer scar-related complications. Our findings suggest that patients with CTS can be effectively managed with ECTR.

Single-cell genomics has advanced rapidly as trace-DNA amplification technologies evolved. However, current technologies are subject to a variety of pitfalls such as contamination, uneven genomic coverage, and amplification errors. Even for the “golden” strategy of single stem cell-derived clonal formation, high-fidelity amplification is applicable merely to single stem cells. It’s still challenging to accurately define somatic mutations of a single cell in various cell types. Herein, we provided evidence, for the first time, to prove that induced pluripotent stem cells (iPS cells or iPSC), being a single somatic cell-derived clone, are recording almost identical (>90%) mutational profile of the initial cell progenitor. This finding demonstrates iPS technique, applicable to any cell type, can be utilized as a cell cloning strategy favorable for single-cell genomic amplification. This novel strategy is not limited by cell-type constraints or amplification artifacts, and thus enables our detailed investigation on the characteristics of somatic mutations in heterogeneous normal cells.

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor. It has been found that autophagy plays a role both as a tumor promoter and inhibitor in HCC carcinogenesis. However, the mechanism behind is still unveiled. This study aims to explore the functions and mechanism of the key autophagy-related proteins, to shed light on novel clinical diagnoses and treatment targets of HCC. Bioinformation analyses were performed by using data from public databases including TCGA, ICGC, and UCSC Xena. The upregulated autophagy-related gene WDR45B was identified and validated in human liver cell line LO2, human HCC cell line HepG2 and Huh-7. Immunohistochemical assay (IHC) was also performed on formalin-fixed paraffin-embedded (FFPE) tissues of 56 HCC patients from our pathology archives. By using qRT-PCR and Western blots we found that high expression of WDR45B influenced the Akt/mTOR signaling pathway. Autophagy marker LC3- II/LC3-I was downregulated, and p62/SQSTM1 was upregulated after knockdown of WDR45B. The effects of WDR45B knockdown on autophagy and Akt/mTOR signaling pathways can be reversed by the autophagy inducer rapamycin. Moreover, proliferation and migration of HCC can be inhibited after the knockdown of WDR45B through the CCK8 assay, wound-healing assay and Transwell cell migration and invasion assay. Therefore, WDR45B may become a novel biomarker for HCC prognosis assessment and potential target for molecular therapy.

Nitrate Transporter 1/Peptide Transporter Family (NPF) genes encode membrane transporters involved in the transport of diverse substrates. However, little is known about the diversity and functions of NPFs in Brassica rapa. In this study, 85 NPFs were identified in B. rapa (BrNPFs) which comprised eight subfamilies. Gene structure and conserved motif analysis suggested that BrNFPs were conserved throughout the genus. Stress and hormone-responsive cis-acting elements and transcription factor binding sites were identified in BrNPF promoters. Syntenic analysis suggested that tandem duplication contributed to the expansion of BrNPFs in B. rapa. Transcriptomic profiling analysis indicated that BrNPF2.6, BrNPF2.15, BrNPF7.6, and BrNPF8.9 were expressed in fertile floral buds, suggesting important roles in pollen development. Thirty-nine BrNPFs were responsive to low nitrate availability in shoots or roots. BrNPF2.10, BrNPF2.19, BrNPF2.3, BrNPF5.12, BrNPF5.16, BrNPF5.8, and BrNPF6.3 were only up-regulated in roots under low nitrate conditions, indicating that they play positive roles in nitrate absorption. Furthermore, many genes were identified in contrasting genotypes that responded to vernalization and clubroot disease. Our results increase understanding of BrNPFs as candidate genes for genetic improvement studies of B. rapa to promote low nitrate availability tolerance and for generating sterile male lines based on gene editing methods.

Objectives: The treatment for neurogenic thoracic outlet syndrome (NTOS) conventionally involves first-rib resection (FRR) surgery, which is quite challenging to perform, especially for novices, and is often associated with postoperative complications. Herein, we report a new segmental resection approach through piezo surgery that involves using a bone cutter, which can uniquely provide a soft tissue protective effect.Methods: This retrospective study involved the examination of 26 NTOS patients who underwent piezo surgery and another group of 30 patients who underwent FRR using the conventional technique. In the patient group that underwent piezo surgery, the rib was first resected into two pieces using a piezoelectric device and subsequently removed. In the patient group that underwent conventional surgery, the first rib was removed as one piece using a rib cutter and rongeurs.Results: The piezo surgery group had significantly shorter operative time (96.85 ± 14.66 vs. 143.33 ± 25.64 min, P < 0.001) and FRR duration (8.73 ± 2.11 vs. 22.23 ± 6.27 min, P < 0.001) than the conventional group. The posterior stump length of the residual rib was shorter in the piezo surgery group than in the conventional group (0.54 ± 0.19 vs. 0.65 ± 0.15 cm, P < 0.05). There were no significant differences in postoperative complications and scores of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, the Cervical Brachial Symptom Questionnaire (CBSQ), and the visual analog scale (VAS). Even the TOS index (NTOS Index = [DASH + (0.83 × CBSQ) + (10 × VAS)]/3) and patient self-assessments of both the groups showed no significant differences. Univariate analyses indicated that the type of treatment affected operative time.Conclusion: Our results suggest that piezo surgery is safe, effective, and simple for segmental FRR in NTOS patients. Piezo surgery provides a more thorough FRR without damaging adjacent soft tissues in a relatively short duration and achieves similar functional recovery as conventional techniques. Therefore, piezo surgery can be a promising alternative for FRR during the surgical treatment of NTOS.

The recent discovery of superconductivity in infinite-layer nickelate films has aroused great interest since it provides a new platform to explore the mechanism of high-temperature superconductivity. However, superconductivity only appears in the thin film form and synthesizing superconducting nickelate films is extremely challenging, limiting the in-depth studies on this compound. Here, we explore the critical parameters in the growth of high-quality nickelate films using molecular beam epitaxy. We found that stoichiometry is crucial in optimizing the crystalline structure and realizing superconductivity in nickelate films. In precursor NdNiO3 films, optimal stoichiometry of cations yields the most compact lattice while off-stoichiometry of cations causes obvious lattice expansion, influencing the subsequent topotactic reduction and the emergence of superconductivity in infinite-layer nickelates. Surprisingly, in-situ reflection high energy electron diffraction indicates that some impurity phases always appear once Sr ions are doped into NdNiO3 although the X-ray diffraction data are of high quality. While these impurity phases do not seem to suppress the superconductivity, their impacts on the electronic and magnetic structure deserve further studies. Our work demonstrates and highlights the significance of cation stoichiometry in the superconducting nickelate family.

Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (PLOD3) is related to a variety of human diseases. However, its function in Colorectal cancer (CRC) remains uncertain. PLOD3 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data. DAVID was used for enrichment analysis of PLOD3-related genes. The correlation between PLOD3 expression and immune cell infiltration was evaluated. Four expression profile datasets (GSE17536, GSE39582, GSE74602, and GSE113513) from Gene Expression Omnibus, and two proteomic datasets were used as validation cohorts for assessing the diagnostic and prognostic value of PLOD3 in CRC. What’s more, we performed immunohistochemistry (IHC) staining for PLOD3 in 160 paired CRC specimens and corresponding adjacent non-tumor tissues. PLOD3 was highly expressed in many tumors including CRC. PLOD3 was upregulated in advanced stage CRCs, and high PLOD3 expression was associated with poor survival. High PLOD3 expression was associated with low levels of B cells, CD4+ T cells, M1 macrophages, CD8+ T cells, and multiple immunerelated characteristics. In addition, the high PLOD3 expression group had a higher TIDE score and a lower tumor mutation burden and microsatellite instability, indicating that patients with high PLOD3 expression may be resistant to immunotherapy. Additional datasets and IHC analysis were used to validate the diagnostic and prognostic value of PLOD3 at the mRNA and protein levels in CRC. Patients with non-response to immunotherapy showed increased PLOD3 expression in an immunotherapy treated dataset. PLOD3 is a potential biomarker for CRC diagnosis and prognosis prediction. CRCs with high PLOD3 expression may be resistant to immune checkpoint therapy.

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer death worldwide. Hence, for a better understanding of tumor microenvironment and to seek for novel molecular targets for esophageal cancer, we performed related studies on two histopathological subtypes of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Bioinformatic analyses were conducted based on the RNA-seq, genomic mutation, and clinical data from TCGA and GEO cohorts. We clustered patients into high-immunity and low-immunity groups through the ssGSEA results. The ESTIMATE algorithm was used to evaluate the tumor microenvironment. Patients with high immunity in both ESCC and EAC had lower tumor purity and poor survival. Subsequently, CIBERSORT was performed to learn about the detailed difference of tumor-infiltrating lymphocytes (TILs) between high- and low-immunity patients. Specific increase of M2 macrophages and decrease of activated dendric cells can be observed in ESCC and EAC, respectively. The most enriched functions and pathways of high-immunity patients were immunoglobulin complex, MHC class II protein complex, and allograft rejection according to the GO terms and KEGG. Two prognostic immune-related multi-lncRNA risk models were constructed and validated by ROC curve and PCA in ESCC and EAC. High-risk patients in both subtypes had poor survival, advanced clinical characteristics, and higher drug susceptibility except cisplatin and sorafenib. In addition, the tumor mutation burden (TMB) was positively correlated with the risk level in the ESCC and EAC and showed distinct differences between the two subtypes. In summary, we comprehensively analyzed the tumor microenvironment for two subtypes of esophageal cancer, identified two multi-lncRNA signatures predictive for the prognosis, and explored the possibility of the signatures to forecast drug susceptibility as well as TMB for the first time. The findings may serve as a conceptual basis for innovative strategy of individualized immunotherapy for esophageal cancer.

Plant-derived natural compounds are widely used as alternative medicine in healthcare throughout the world. Ginkgolic acids, the phenolic compounds isolated from the leaves and seeds of Ginkgo biloba, are among the chemicals that have been explored the most. Ginkgolic acids exhibit cytotoxic activity against a vast number of human cancers in various preclinical models in vitro and in vivo. Additionally, the pharmacological activities of ginkgolic acids are also involved in antidiabetic, anti-bacteria, anti-virus, anti-fibrosis, and reno/neuroprotection. Autophagy as a highly conserved self-cleaning process that plays a crucial role in maintaining cellular and tissue homeostasis and has been proven to serve as a protective mechanism in the pathogenesis of many diseases, including neurodegenerative diseases, cancer, and infectious diseases. In this review, we surveyed the pharmacological activities of the major three forms of ginkgolic acids (C13:0, C15:1, and C17:1) that are linked to autophagic activity and the mechanisms to which these compounds may participate. A growing body of studies in last decade suggests that ginkgolic acids may represent promising chemical compounds in future drug development and an alternative remedy in humans.

The lightweight property of helical composite spring (HCS) applied in the transportation field has attracted more and more attention recently. However, it is difficult to maintain stiffness and fatigue resistance at the same time. Herein, inspired by collagen fibers in bone, a bionic basalt fiber/epoxy resin helical composite spring is manufactured. The collagen fibers consist of nanoscale hydroxyapatite (increases stiffness) and collagen molecules composed of helical amino acid chains (can increase fatigue resistance). Such a helical structure of intercalated crystals ensures that bone has good resistance to fracture. Specifically, we first investigated the effect of adding different contents of NS to basalt fibers on the stiffness and fatigue properties of an HCS. The results show that the optimal NS content of 0.4 wt% resulted in 52.1% and 43.5% higher stiffness and fatigue properties of an HCS than those without NS, respectively. Then, two braided fiber bundles (TS-BFB) and four braided fiber bundles (FS-BFB) were designed based on the helical structure of amino acid chains, and the compression tests revealed that the maximum load resistance of TS-BFB and FS-BFB was increased by 29.2% and 44%, respectively, compared with the conventional single fiber bundle (U-BFB). The superior mechanical performance of TS-BFB and FS-BFB is attributed to the more adequate bonding of 0.4 wt% NS to the epoxy resin and the multi-fiber bundles that increase the transverse fiber content of the spring. The findings in this work introduce the bionic collagen fiber structure into the design for an HCS and provide a new idea to improve the spring performance.

The relatively low photo-conversion efficiencies of semiconductors greatly restrict their real-world practices toward photoelectrochemical water splitting. In this work, we demonstrate the fabrication of TiO2-x nanorod arrays enriched with oxygen defects and surface-polarized hydroxyl groups by a facile surface reduction method. The oxygen defects located in the bulk/surface of TiO2-x enable fast charge transport and act as catalytically active sites to accelerate the water oxidation kinetics. Meanwhile, the hydroxyl groups could establish a surface electric field by polarization, for efficient charge separation. The as-optimized TiO2-x nanorod photoanode achieves a high photocurrent density of 2.62 mA cm−2 without any cocatalyst loading at 1.23 VRHE under 100 mW cm−2, which is almost double that of the bare TiO2 counterpart. Notably, the surface charge separation and injection efficiency of the TiO2-x photoanode reach as high as 80% and 97% at 1.23 VRHE, respectively, and the maximum incident photon-to-current efficiency reaches 90% at 400 nm. This work provides a new surface treatment strategy for the development of high-performance photoanodes in photoelectrochemical water splitting.

Although emotional audiovisual integration has been investigated previously, whether emotional audiovisual integration is affected by the spatial allocation of visual attention is currently unknown. To examine this question, a variant of the exogenous spatial cueing paradigm was adopted, in which stimuli varying by facial expressions and nonverbal affective prosody were used to express six basic emotions (happiness, anger, disgust, sadness, fear, surprise) via a visual, an auditory, or an audiovisual modality. The emotional stimuli were preceded by an unpredictive cue that was used to attract participants’ visual attention. The results showed significantly higher accuracy and quicker response times in response to bimodal audiovisual stimuli than to unimodal visual or auditory stimuli for emotional perception under both valid and invalid cue conditions. The auditory facilitation effect was stronger than the visual facilitation effect under exogenous attention for the six emotions tested. Larger auditory enhancement was induced when the target was presented at the expected location than at the unexpected location. For emotional perception, happiness shared the biggest auditory enhancement among all six emotions. However, the influence of exogenous cueing effect on emotional perception seemed to be absent.