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Targeting the oxytocin (OXT) peptide system has emerged as a promising new approach for the treatment of alcohol use disorder (AUD). However, further advancements in this development depend on properly modeling various complex social aspects of AUD and its treatment. Here we examined behavioral and molecular underpinnings of OXT receptor (OXTR) agonism in prairie voles, a rodent species with demonstrated translational validity for neurobiological mechanisms regulating social affiliations. To further improve translational validity of these studies, we examined effects of intranasal (IN) OXT administration in male and female prairie voles socially housed in the presence of untreated cagemates. IN OXT selectively inhibited alcohol drinking in male, but not female, animals. Further, we confirmed that exogenously administered OXT penetrates the prairie vole brain and showed that Receptor for Advanced Glycation End-products assists this penetration after IN, but not intraperitoneal (IP), OXT administration. Finally, we demonstrated that IP administration of LIT-001, a small-molecule OXTR agonist, inhibits alcohol intake in male, but not female, prairie voles socially housed in the presence of untreated cagemates. Taken together, results of this study support the promise of selectively targeting OXTR for individualized treatment of AUD.

To compare the short-term outcomes of a new gastrointestinal decompression tube combined with conservative treatment in patients with esophagojejunal anastomotic leakage (EJAL) after total gastrectomy. We retrospectively analyzed the data of 81 patients with EJAL who had undergone total gastrectomy and Roux-en-Y reconstruction at Fujian Medical University Union Hospital between January 2014 and December 2021. The patients were divided into experimental (12 patients with new gastrointestinal decompression tube plus conservative treatment) and control (69 patients with conservative treatment) groups, according to the different treatment methods they received. Anatomic defect size linearly correlated with time to clinical success, hospital stay, and hospital cost in the control group. The two groups showed no significant differences in anastomotic defect size, time of defect after surgery, hospitalization cost, and time of antibiotic use. However, the time to clinical success was significantly shorter in the experimental group than in the control group (16.0 ± 8.3 vs. 23.6 ± 17.8, P = 0.04), as was the length of hospital stay (30.1 ± 6.3 vs. 36.8 ± 16.7, P = 0.017). Furthermore, when the defect size was ≥ 4 mm, the time to clinical success, hospital stay, and hospital cost in the experimental group were lower than those in the control group (P 0.05). Placement of a new gastrointestinal decompression tube is a safe treatment. When the defect size is ≥ 4 mm, the time to clinical success, length of hospital stay, and hospital cost can be reduced.

Water-based anti-corrosion coatings, which are environmentally-friendly replacements for organic solvent-based coatings, do not perform well enough for use in the most challenging corrosion environments. The high water absorption capacity of water-based latex films may reduce barrier performance by contributing to corrosive reactant/product transport. We seek to understand the coupled effects of water absorption and ion transport in hydrated latex films, and to propose mechanisms explaining these effects. Water absorption and ion transport in films immersed in deionized (DI) water were monitored by mass gain and electrical conductivity measurements, respectively. Despite very similar polymer compositions between films, large differences in water absorption and ion transport rates were observed and explained by percolating networks at latex particle boundaries which facilitate transport. A semi-continuum model with three-component diffusion and convection-like elastic relaxation supported the assumptions of the physical mechanisms governing water absorption and ion transport. The evidence of the coupled processes of water absorption and ion transport in hydrated latex films revealed in this study are useful for designing water-based coatings that provide high levels of corrosion resistance.

There is insufficient evidence to evaluate the long-term outcomes of robotic radical gastrectomy. The aim of this study was to compare the radical results and long-term outcomes of robotic and laparoscopic radical gastrectomy.We prospectively collected and retrospectively analyzed the general clinicopathological data of gastric cancer patients treated with robotic radical gastrectomy (RG) and laparoscopic radical gastrectomy (LG) from July 2016 to July 2018 at Fujian Medical University Union Hospital. The RG cohort was matched 1:3 with the LG cohort by using propensity score matching (PSM). The primary endpoints of the study were 3-year overall survival (OS) and 3-year relapse-free survival (RFS).The study included 221 patients treated with RG and 1106 patients treated with LG for gastric cancer. After PSM, 211 patients were included in the RG cohort, and 663 patients were included in the LG cohort. The 3-year OS rate was 81.0% in the robotic cohort and 79.3% in the laparoscopic cohort (log-rank test, P = 0.516). The 3-year RFS rate was 78.7% in the robotic cohort and 75.6% in the laparoscopic cohort (log-rank test, P = 0.600). In the subgroup analyses, no significant differences were noted between the RG and LG cohorts in terms of 3-year OS and 3-year RFS (all P 0.05). The therapeutic value index of each lymph node station dissection in the robotic cohort was comparable to that in the laparoscopic cohort.Robotic radical gastrectomy can achieve radical results and long-term outcomes comparable to laparoscopic surgery, and further multicenter prospective studies can be conducted to assess the clinical efficacy of robotic radical gastrectomy.

Robotic surgery may be advantageous for complex surgery. We aimed to compare the intraoperative and postoperative short-term outcomes of spleen-preserving splenic hilar lymphadenectomy (SPSHL) during robotic and laparoscopic total gastrectomy.From July 2016 to December 2020, the clinicopathological data of 115 patients who underwent robotic total gastrectomy combined with robotic SPSHL (RSPSHL) and 697 patients who underwent laparoscopic total gastrectomy combined with laparoscopic SPSHL (LSPSHL) were retrospectively analyzed. A 1:2 ratio propensity score matching (PSM) was used to balance the differences between the two groups to compare their outcomes. The Generic Error Rating Tool was used to evaluate the technical performance.After PSM, the baseline preoperative characteristics of the 115 patients in the RSPSHL and 230 patients in the LSPSHL groups were balanced. The dissection time of the region of the splenic artery trunk (5.4 ± 1.9 min vs. 7.8 ± 3.6 min, P 0.001), the estimated blood loss during SPSHL (9.6 ± 4.8 ml vs. 14.9 ± 7.8 ml, P 0.001), and the average number of intraoperative technical errors during SPSHL (15.1 ± 3.4 times/case vs. 20.7 ± 4.3 times/case, P 0.001) were significantly lower in the RSPSHL group than in the LSPSHL group. The RSPSHL group showed higher dissection rates of No. 10 (78.3% vs. 70.0%, P = 0.104) and No. 11d (54.8% vs. 40.4%, P = 0.012) lymph nodes and significantly improved postoperative recovery results in terms of times to ambulation, first flatus, and first intake (P 0.05). The splenectomy rates of the two groups were similar (1.7% vs. 0.4%, P = 0.539), and there was no significant difference in morbidity and mortality within postoperative 30 days (13.0% vs. 15.2%, P = 0.589).Compared to LSPSHL, RSPSHL has more advantages in terms of surgical qualities and postoperative recovery process with similar morbidity and mortality. For complex SPSHL, robotic surgery may be a better choice.

C-to-G base editors have been successfully constructed recently, but limited work has been done on concurrent C-to-G and A-to-G base editing. In addition, there is also limited data on how chromatin-associated factors affect the base editing. Here, we test a series of chromatin-associated factors, and chromosomal protein HMGN1 was found to enhance the efficiency of both C-to-G and A-to-G base editing. By fusing HMGN1, GBE and ABE to Cas9, we develop a CRISPR-based dual-function A-to-G and C-to-G base editor (GGBE) which is capable of converting simultaneous A and C to G conversion with substantial editing efficiency. Accordingly, the HMGN1 role shown in this work and the resulting GGBE tool further broaden the genome manipulation capacity of CRISPR-directed base editors.

Background COVID-19, which is caused by SARS-CoV-2, is a major global health threat. The dominant variant of SARS-CoV-2 has changed over time due to continuous evolution. We aimed to evaluate the coverage of SARS-CoV-2 vaccination among employees in China, explore their willingness to receive the SARS-CoV-2 variant vaccine and examine the potential factors influencing vaccination coverage and willingness. Methods A cross-sectional epidemiological survey was conducted online from January 1, 2022, to January 30, 2022. The information collected in the survey included sociodemographic characteristics, lifestyle habits, vaccination coverage, willingness to be vaccinated against SARS-CoV-2 variants and the reasons for vaccination and willingness. Multivariable logistic regression models were used to assess the associations of potential factors with the rate of vaccination and the willingness to be vaccinated. Results Among 62,395 eligible participants, the coverage of SARS-CoV-2 vaccination was 98.9% for at least one dose and 70.1% for a booster. The great majority of vaccinated individuals (94.4%) voluntarily received the vaccine. A total of 60,694 respondents (97.7%) were willing to be vaccinated against SARS-CoV-2 variants, mainly due to confidence in the effectiveness of vaccines (92.8%). A total of 1431 respondents were unwilling to be vaccinated, mainly because of concerns about the adverse effects of vaccines (77.6%). Longer education duration was associated with a higher rate of SARS-CoV-2 vaccination and willingness to be vaccinated. General or poor health status and having no history of influenza vaccination were associated with a lower rate of SARS-CoV-2 vaccination and willingness to be vaccinated. Additionally, we observed a significant positive association of abuse experience with the willingness to be vaccinated. Conclusion Although the rate of SARS-CoV-2 vaccination and the willingness to be vaccinated were relatively high in the study population, there were still some respondents with vaccine hesitancy. Relevant strategies based on significant related factors should be developed and implemented to encourage vaccination.

Protonic ceramic electrochemical cells hold promise for operation below 600 °C (refs.

Polymyositis (PM) is a chronic autoimmune connective tissue disease whose pathogenic mechanisms are unclear. This study aimed to identify the main genes and functionally enriched pathways involved in PM using weighted gene coexpression network analysis (WGCNA).To identify the candidate genes of PM, microarray datasets GSE128470, GSE3112, GSE39454 and GSE125977 were obtained from the Gene Expression Omnibus database. The gene network of GSE128470 was constructed, and WGCNA was used to divide genes into different modules. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were applied to the most PM-related modules. The datasets were used to verify the expression profile and diagnostic capabilities of the hub genes. Additionally, gene set enrichment analysis (GSEA) was carried out. Moreover, gene signatures were then used as a search query to explore the connectivity map (CMap).A weighted gene coexpression network was constructed, and the genes were divided into 66 modules. The enriched functions and candidate pathway modules included interferon-γ, type I interferon, cellular response to interferon-γ, neutrophil activation, neutrophil degranulation, neutrophil-mediated immunity and neutrophil activation involved in the immune response. A total of 22 hub genes were identified. The Mann-Whitney U test was performed on these 22 genes using the three datasets of muscle samples and one dataset of whole blood samples, and two genes significantly differentially expressed in all datasets were obtained: VCAM1 and LY96. Receiver operating characteristic curve analysis determined that VCAM1 and LY96 gene expression can distinguish PM from healthy controls (the area under the curve [AUC] was greater than 0.75). Logistic regression analysis was performed on the combination of LY96 and VCAM1. The accuracy, sensitivity, specificity, and AUC of the combination reached 1.0. GSEA of VCAM1 and LY96 revealed their relation to 'inflammatory response', 'TNF-α signalling via NF-κB', 'complement' and 'myogenesis'. CMap research revealed a few compounds with the potential to counteract the effects of the dysregulated molecular signature in PM.We used WGCNA to observe all aspects of PM, which helped to elucidate the molecular mechanisms of PM onset and progression and provide candidate targets for the diagnosis and treatment of PM. Key Points • Four microarray datasets were analysed in patients with polymyositis and healthy controls, and VCAM1 and LY96 were significant genes in all datasets. • GSEA of VCAM1 and LY96 revealed that they were mainly related to 'inflammatory response', 'TNF-α signalling via NF-κB', 'complement' and 'myogenesis'. • CMap found a few compounds such as dimethyloxalylglycine and HNMPA-(AM)3 with the potential to counteract the effects of the dysregulated molecular signature in PM.

Prime editing is a versatile gene editing tool that enables precise sequence changes of all types in the genome, but its application is rather limited by the editing efficiency. Here, we first apply the Suntag system to recruit the transcription factor P65 and enhance the desired editing outcomes in the prime editing system. Next, MS2 hairpins are used to recruit MS2-fused P65 and confirmed that the recruitment of the P65 protein could effectively improve the prime editing efficiency in both the PE3 and PE5 systems. Moreover, this suggests the increased editing efficiency is most likely associated with the induction of chromatin accessibility change by P65. In conclusion, we apply different systems to recruit P65 and enhance the prime editing efficiency of various PE systems. Furthermore, our work provides a variety of methods to work as protein scaffolds for screening target factors and thus supports further optimization of prime editing systems.

Electroplated Cu has been extensively applied in advanced electronic packaging, and its mechanical properties are critical for reliability. In this study, Cu foils fabricated through electroplating with various bis-(3-sulfopropyl) disulfide (SPS) concentrations are examined using tensile tests. The SPS concentration affects the grain size of the electroplated Cu foils, resulting in different mechanical properties. A significant Hall–Petch effect, $${\sigma }_{y} = 197.4 + 0.12{d}^{\frac{-1}{2}}$$ σ y = 197.4 + 0.12 d - 1 2 , is demonstrated for the electroplated Cu foils. The different concentrations of impurities identified through time-of-flight secondary ion mass spectrometry correspond to the different grain sizes, determining the transgranular and intergranular fracture during the tensile test. The results demonstrate that the SPS concentration controlling the microstructures of the electroplated Cu results in a Hall–Petch effect on the mechanical properties of the electroplated Cu foils.

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder. Identifying individuals at increased risk of developing AD is important for early intervention. Using data from the Alzheimer Disease Genetics Consortium, we constructed polygenic risk scores (PRSs) for AD and age-at-onset (AAO) of AD for the UK Biobank participants. We then built machine learning (ML) models for predicting development of AD, and explored feature importance among PRSs, conventional risk factors, and ICD-10 codes from electronic health records, a total of > 11,000 features using the UK Biobank dataset. We used eXtreme Gradient Boosting (XGBoost) and SHapley Additive exPlanations (SHAP), which provided superior ML performance as well as aided ML model explanation. For participants age 40 and older, the area under the curve for AD was 0.88. For subjects of age 65 and older (late-onset AD), PRSs were the most important predictors. This is the first observation that PRSs constructed from the AD risk and AAO play more important roles than age in predicting AD. The ML model also identified important predictors from EHR, including urinary tract infection, syncope and collapse, chest pain, disorientation and hypercholesterolemia, for developing AD. Our ML model improved the accuracy of AD risk prediction by efficiently exploring numerous predictors and identified novel feature patterns.

Fundamentally understanding the complex electrochemical reactions that are associated with energy devices (e.g., rechargeable batteries, fuel cells and electrolyzers) has attracted worldwide attention. In situ liquid cell transmission electron microscopy (TEM) offers opportunities to directly observe and analyze in-liquid specimens without the need for freezing or drying, which opens up a door for visualizing these complex electrochemical reactions at the nano scale in real time. The key to the success of this technique lies in the design and fabrication of electrochemical liquid cells with thin but strong imaging windows. This protocol describes the detailed procedures of our established technique for the fabrication of such electrochemical liquid cells (~110 h). In addition, the protocol for the in situ TEM observation of electrochemical reactions by using the nanofabricated electrochemical liquid cell is also presented (2 h). We also show and analyze experimental results relating to the electrochemical reactions captured. We believe that this protocol will shed light on strategies for fabricating high-quality TEM liquid cells for probing dynamic electrochemical reactions in high resolution, providing a powerful research tool. This protocol requires access to a clean room equipped with specialized nanofabrication setups as well as TEM characterization equipment.

Background Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach that includes targeted agents and immunotherapy. Although the response to targeted therapies for unresectable hepatocellular carcinoma (HCC) is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects continue to be problematic. Given that immune checkpoint inhibitor alone are not robust enough to improve survival in unresectable HCC, growing evidence supports the combination of targeted therapy and immunotherapy with synergistic effect. Methods Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (version 1.1) for unresectable HCC patients, an Eastern Cooperative Oncology Group performance status of 0–2, and a Child–Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). Results Three phase II/III randomized controlled trials were included in this study. The pooled results showed that combination therapy significantly improved survival than targeted monotherapy, in terms of OS (hazard ratio (HR) = 0.67; 95% confidence interval [CI]: 0.50–0.91) and PFS (HR = 0.58; 95% CI: 0.51–0.67), respectively. In the incidence of grade 3–5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (odds ratio = 1.98; 95% CI: 1.13–3.48). Conclusion For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared with targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.

For the development of a parallel mechanism (PM), it is necessary to establish a dynamic model which can accurately meet the requirements of real-time control. Compared with the general dynamic analysis model based on the inverse kinematics, the dynamic analysis model based on the forward kinematics has the advantage of low-complexity. In this paper, a new type of 3-DOF PM with analytical forward displacement analysis is proposed. Different from the general dynamic analysis based on the inverse kinematics, the displacement, velocity and acceleration equations of the PM are established and solved by forward kinematics. The inverse dynamic equation of the PM is constructed and solved by analyzing the forces on each link and based on Newton-Euler method. Then the theoretical results of an example are compared with the simulation results, which shows that the simulation results are basically consistent with the theoretical results. And the maximum error of the driving force of each pair is 1.32%, 5.8% and 5.2%, respectively, which verifies the correctness of the dynamic model. The PM has a potential application prospect in the grasping, spraying and picking of workpieces. The research results of this paper provide a theoretical basis for the design, manufacture and application of the PM.

Traumatic brain injury causes inflammation and glial scarring that impede brain tissue repair, so stimulating angiogenesis and recovery of brain function remain challenging. Here we present an adaptable conductive microporous hydrogel consisting of gold nanoyarn balls-coated injectable building blocks possessing interconnected pores to improve angiogenesis and recovery of brain function in traumatic brain injury. We show that following minimally invasive implantation, the adaptable hydrogel is able to fill defects with complex shapes and regulate the traumatic brain injury environment in a mouse model. We find that placement of this injectable hydrogel at peri-trauma regions enhances mature brain-derived neurotrophic factor by 180% and improves angiogenesis by 250% in vivo within 2 weeks after electromagnetized stimulation, and that these effects facilitate neuron survival and motor function recovery by 50%. We use blood oxygenation level-dependent functional neuroimaging to reveal the successful restoration of functional brain connectivity in the corticostriatal and corticolimbic circuits.

Rechargeable solid-state Li metal batteries demand ordered flows of Li-ions and electrons in and out of solid structures, with repeated waxing and waning of LiBCC phase near contact interfaces which gives rise to various electro-chemo-mechanical challenges. There have been approaches that adopt three-dimensional (3D) nanoporous architectures consisting of mixed ion-electron conductors (MIECs) to combat these challenges. However, there has remained an issue of LiBCC nucleation at the interfaces between different solid components (e.g., solid electrolyte/MIEC interface), which could undermine the interfacial bonding, thereby leading to the evolution of mechanical instability and the loss of ionic/electronic percolation. In this regard, the present work shows that the Li-ion and electron insulators (LEIs) that are thermodynamically stable against LiBCC could combat such challenges by blocking transportation of charge carriers on the interfaces, analogous to dielectric layers in transistors. We searched the ab initio database and have identified 48 crystalline compounds to be LEI candidates (46 experimentally reported compounds and 2 hypothetical compounds predicted to be stable) with a band gap greater than 3 eV and vanishing Li solubility. Among these compounds, those with good adhesion to solid electrolyte and mixed ion-electron conductor of interest, but are lithiophobic, are expected to be the most useful. We also extended the search to Na or K metal compatible alkali-ion and electron insulators, and identified some crystalline compounds with a property to resist corresponding alkali-ions and electrons.

This study evaluated the safety, effectiveness, and feasibility of indocyanine green (ICG) tracing in guiding lymph-node (LN) dissection during laparoscopic D2 radical gastrectomy in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC). We retrospectively analyzed data on 313 patients with clinical stage of cT1-4N0-3M0 who underwent laparoscopic radical gastrectomy after NAC between February 2010 and October 2020 from two hospitals in China. Grouped according to whether ICG was injected. For the ICG group (n = 102) and non-ICG group (n = 211), 1:1 propensity matching analysis was used. After matching, there was no significant difference in the general clinical pathological data between the two groups (ICG vs. non-ICG: 94 vs. 94). The average number of total LN dissections was significantly higher in the ICG group and lower LN non-compliance rate than in the non-ICG group. Subgroup analysis showed that among patients with LN and tumor did not shrink after NAC, the number of LN dissections was significantly more and LN non-compliance rate was lower in the ICG group than in the non-ICG group. Intraoperative blood loss was significantly lesser in the ICG group than in the non-ICG group, while the recovery and complications of the two groups were similar. For patients with poor NAC outcomes, ICG tracing can increase the number of LN dissections during laparoscopic radical gastrectomy, reduce the rate of LN non-compliance, and reduce intraoperative bleeding. Patients with AGC should routinely undergo ICG-guided laparoscopic radical gastrectomy.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet count. While corticosteroids are a useful first-line therapy for ITP patients, their long-term effectiveness is limited, and the determinants of corticosteroid sensitivity in ITP patients remain largely unknown. Sirtuin 1 (SIRT1), a member of the mammalian sirtuin family, is related to the anti-inflammatory effects of corticosteroids. Here, we investigate the contribution of the SIRT1 single-nucleotide polymorphisms (SNPs) rs12778366 and rs4746720 to ITP susceptibility. We recruited 330 ITP patients and 309 healthy controls from Han population, and performed genotyping of SIRT1 rs12778366 and rs4746720 using a MassARRAY system. The results were validated in another 55 ITP patients from ethnic minorities. Using clinical data of patients and controls from Han polulation, including corticosteroid sensitivity, susceptibility, refractoriness, and severity, our results revealed that the CC/TC genotypes of SIRT1 rs12778366 were associated with a 2.034-fold increased risk of corticosteroid resistance compared to the homozygous major TT genotype (dominant, CC/TC vs. TT, OR = 2.034, 95% CI = 1.039–3.984, p = 0.038). In contrast, the CC/CT genotype of SIRT1 rs4746720 showed a 0.560-fold decreased risk of corticosteroid resistance (dominant, 95% CI = 0.321–0.976, OR = 0.560, p = 0.041). The C allele substitute in SIRT1 rs12778366 was significantly associated with the corticosteroid sensitivity of ITP patients (p = 0.021). The similar results were obtained in minority ITP patients. This study indicates that SIRT1 rs12778366 and rs4746720 may be genetic factors related to corticosteroid sensitivity in ITP patients.

Constant DNA damage occurs in cells, and the cells are programmed to respond constitutively. This study explored the roles of ataxia-telangiectasia mutated interactor (ATMIN), one of the impaired pathways involving the DNA damage response (DDR) in mismatch repair-deficient [microsatellite instability (MSI)-high] colorectal carcinoma (CRC). Expression of ATMIN messenger RNA (mRNA) was detected in CRC specimens with microsatellite instability (MSI) characteristics. The effects of ectopic ATMIN expression and ATMIN knockdown on invasion abilities were evaluated in MSI-high cell lines, and liver metastasis ability was investigated in vivo. Protein-protein interactions were assessed by coimmunoprecipitation analyses in vitro. Decreased ATMIN expression was positively correlated with advanced stage of disease (P < 0.05), lymph node metastases (P < 0.05), and deeper invasion (P < 0.05) in MSI-high tumors. Transient or stable ATMIN knockdown significantly increased cell motility. Moreover, in the high-throughput microarray and gene set enrichment analysis, ATMIN was shown to act on the Wnt-signaling pathway via PARP1. This cascade influences β-catenin/transcription factor 4 (TCF4) binding affinity in MSI-high tumors, and PARP1 inhibition significantly decreased the number of metastases from ATMIN knockdown cancer cells. The results not only indicated the critical role of ATMIN, but also shed new light on PARP1 inhibitors, providing a basis for further clinical trials of MSI-high CRC.

Background Cerebral infarction (CI) is an unusual complication in patients with bleeding disorders. To our knowledge, this is the first case of postoperative internal border-zone infarction (I-BZI) from Hemophilia A. Case presentation We present a case of Hemophilia A developing I-BZI, after surgical treatment of giant hemophilic pseudotumor. A 36-year-old man was introduced from other hospital by Hemophilia with giant hemophilic pseudotumor in his left thigh. Patient and his relatives did not have a history of thrombophilia. After excluding the relevant surgical contraindications, we performed the operation of pseudotumor resection. Prior to surgery, blood tests revealed hemoglobin of 137 g/L. FVIII activity was 1.5%. Activated partial thromboplastin time (APTT) was 71.50 s and D-dimer was 3.33 mg/L FEU. Immediately before surgery, the patient received an intravenous infusion of FVIII products (Xyntha®) at a dose of 3500 IU for his body weight of 80 kg. Post-operative day two (POD2), patient developed vomiting, decreased response, and dysarthria. Hemoglobin was 54 g/L with blood pressure of 110/70 mmHg. Magnetic resonance imaging of the brain showed there were multiple acute cerebral infarctions in bilateral lateral ventricles (internal border zone) and multiple ischemic foci in the white matter areas and basal ganglia of the bilateral cerebral hemispheres. This case suggested that acute severe anemia can be one of the causes of I-BZI. Conclusions For the treatment of I-BZI caused by acute anemia from Hemophilia A, volume expansion, red blood cell supplement and continuous improvement of coagulation with suitable dose of factor VIII (FVIII) should be considered to improve prognosis.

Inflammasomes are cytosolic signaling complexes capable of sensing microbial ligands to trigger inflammation and cell death responses. Here, we show that guanylate-binding proteins (GBPs) mediate pathogen-selective inflammasome activation. We show that mouse GBP1 and GBP3 are specifically required for inflammasome activation during infection with the cytosolic bacterium Francisella novicida. We show that the selectivity of mouse GBP1 and GBP3 derives from a region within the N-terminal domain containing charged and hydrophobic amino acids, which binds to and facilitates direct killing of F. novicida and Neisseria meningitidis, but not other bacteria or mammalian cells. This pathogen-selective recognition by this region of mouse GBP1 and GBP3 leads to pathogen membrane rupture and release of intracellular content for inflammasome sensing. Our results imply that GBPs discriminate between pathogens, confer activation of innate immunity, and provide a host-inspired roadmap for the design of synthetic antimicrobial peptides that may be of use against emerging and re-emerging pathogens.

Nonlinear light-matter interaction, as the core of ultrafast optics, bulk photovoltaics, nonlinear optical sensing and imaging, and efficient generation of entangled photons, has been traditionally studied by first-principles theoretical methods with the sum-over-states approach. However, this indirect method often suffers from the divergence at band degeneracy and optical zeros as well as convergence issues and high computation costs when summing over the states. Here, using shift vector and shift current conductivity tensor as an example, we present a gauge-invariant generalized approach for efficient and direct calculations of nonlinear optical responses by representing interband Berry curvature, quantum metric, and shift vector in a generalized Wilson loop. This generalized Wilson loop method avoids the above cumbersome challenges and allows for easy implementation and efficient calculations. More importantly, the Wilson loop representation provides a succinct geometric interpretation of nonlinear optical processes and responses based on quantum geometric tensors and quantum geometric potentials and can be readily applied to studying other excited-state responses., Comment: 20 pages, 10 figures

Hard and brittle materials usually exhibit a much lower strength when loaded in tension than in compression. However, this common-sense behaviour may not be intrinsic to these materials, but arises from their higher flaw sensitivity to tensile loading. Here, we demonstrate a reversed and unusually pronounced tension–compression asymmetry (tensile strength exceeds compressive strength by a large margin) in submicrometre-sized samples of isotropic amorphous silicon. The abnormal asymmetry in the yield strength and anelasticity originates from the reduction in shear modulus and the densification of the shear-activated configuration under compression, altering the magnitude of the activation energy barrier for elementary shear events in amorphous Si. In situ coupled electrical tests corroborate that compressive strains indeed cause increased atomic coordination (metallization) by transforming some local structures from sp3-bonded semiconducting motifs to more metallic-like sites, lending credence to the mechanism we propose. This finding opens up an unexplored regime of intrinsic tension–compression asymmetry in materials. Submicrometre-sized amorphous silicon samples show an unusually large tensile strength relative to the compressive strength, which is due to the reduced shear modulus and the activation energy barrier for shear transformations under compression.

In order to improve the current environmental pollution caused by discarded pesticide packages in rural areas, and raise awareness of agricultural ecological environmental protection. Rare earth ions (RE3+ = Ce3+, Sm3+, Pr3+, La3+) doped titanium dioxide (TiO2) catalysts were prepared by sol-hydrothermal method and characterized by XRD, SEM, TEM, XPS, BET, UV–vis DRS, PL, EPR, and density functional theory (DFT) calculations. The characterization results showed that the doped rare earth ions replace Ti4+ into the titania lattice. The activity of the RE3+-doped TiO2 photocatalyst was evaluated by degrading methyl orange (MO) and mixed pesticides (also containing pirimicarb, fenthiophos, triadimefon and deltamethrin) under ultraviolet light. Compared with pure TiO2, RE3+-doped TiO2 has significantly improved photocatalytic activity for the degradation of MO and carbamate pesticides. The degradation rate of Sm-TiO2 sample to degrade MO reached 100% within 60 min, and the degradation rate of degrading aphicarb, fenthion, triadimefon and deltamethrin reached more than 90% within 180 min. Sm-TiO2 is the best catalyst. This can be attributed to a synergistic effect of the doping of Sm3+ introduces impurity energy levels and a large number of oxygen vacancies (OVs), which can more effectively capture photogenerated electrons and reduce the recombination rate of photogenerated electrons-holes. In this study, the sol-hydrothermal method was used to develop a high-efficiency catalyst for simultaneous photocatalytic degradation of various organic pollutants in aqueous solutions.

Advanced beyond-silicon electronic technology requires both channel materials and also ultralow-resistance contacts to be discovered1,2. Atomically thin two-dimensional semiconductors have great potential for realizing high-performance electronic devices1,3. However, owing to metal-induced gap states (MIGS)4–7, energy barriers at the metal–semiconductor interface—which fundamentally lead to high contact resistance and poor current-delivery capability—have constrained the improvement of two-dimensional semiconductor transistors so far2,8,9. Here we report ohmic contact between semimetallic bismuth and semiconducting monolayer transition metal dichalcogenides (TMDs) where the MIGS are sufficiently suppressed and degenerate states in the TMD are spontaneously formed in contact with bismuth. Through this approach, we achieve zero Schottky barrier height, a contact resistance of 123 ohm micrometres and an on-state current density of 1,135 microamps per micrometre on monolayer MoS2; these two values are, to the best of our knowledge, the lowest and highest yet recorded, respectively. We also demonstrate that excellent ohmic contacts can be formed on various monolayer semiconductors, including MoS2, WS2 and WSe2. Our reported contact resistances are a substantial improvement for two-dimensional semiconductors, and approach the quantum limit. This technology unveils the potential of high-performance monolayer transistors that are on par with state-of-the-art three-dimensional semiconductors, enabling further device downscaling and extending Moore’s law. Electric contacts of semimetallic bismuth on monolayer semiconductors are shown to suppress metal-induced gap states and thus have very low contact resistance and a zero Schottky barrier height.

Glycine is an amino acid with a diverse array of health benefits regarding metabolism, immunity, and development. The aim of this study was to test the hypothesis that glycine supplementation alters the intestinal microbial composition and improves the intestinal mucosal immunity of weaned piglets. One hundred and twenty-eight weaned piglets divided into 4 groups were fed with a corn- and soybean meal-based diet supplemented with 0 (control), 0.5, 1, or 2% glycine for 7 days. The intestinal microbiota and tissue samples from the control and the 2% glycine-supplemented piglets were collected for determination of the composition of microbial community and the intestinal mucosal barrier function. Piglets fed with diet containing 2% glycine, instead of 0.5% or 1% glycine, presented elevated average daily gain and feed conversion ratio, as compared with the control. 2% glycine enhanced the abundance of mucins in the jejunum and ileum and mRNA level of porcine β-defensin (pBD) 2 and pBD-3, as well as the protein level of secretory immunoglobulin A (sIgA) in the jejunum. The mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and the protein level of phosphorylated p38 mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), nuclear factor (NF)-κB p65, and claudin-2 in the jejunum were lower in the 2% glycine group than that in the control. In addition, an elevated ratio of CD4+/CD8+ T lymphocytes was observed in the jejunum of piglets receiving diet supplemented with 2% glycine. The colon content of piglets fed with 2% glycine exhibited a reduction in abundance of pathogenic bacteria (Escherichia-Shigella, Clostridium, and Burkholderiales) and an increase in short-chain fatty acid-producing bacteria (Blautia, Lachnospiraceae, Anaerostipes, and Prevotella) in comparison with the control. We conclude that dietary supplementation with 2% glycine improves the intestinal immunological barrier function and the microbial composition, therefore, contributing to the growth performance of weaned piglets.

The discovery and control of new phases of matter is a central endeavour in materials research. The emergence of atomically thin 2D materials, such as transition-metal dichalcogenides and monochalcogenides, has allowed the study of diffusive, displacive and quantum phase transitions in 2D. In this Review, we discuss the thermodynamic and kinetic features of 2D phase transitions arising from dimensionality confinement, elasticity, electrostatics, defects and chemistry unique to 2D materials. We highlight polymorphic, ferroic and high-temperature diffusive phase changes, and examine the technological potential of controlled 2D phase transitions. Finally, we give an outlook to future opportunities in the study and applications of 2D phase transitions, and identify key challenges that remain to be addressed. Phase transformations in 2D materials have distinct kinetic and thermodynamic features, resulting from their reduced dimensionality and unique interactions. This Review discusses the properties of phase transitions and defects in 2D materials, and examines technological applications and challenges in the study of 2D phase transitions.

Artificial carbon fixation contributes to closing the anthropogenic carbon cycle. However, large-scale conversion of CO2 into selective products remains a challenge. Coupled thermal–electrochemical catalysis could offer an attractive approach to upgrading CO2 into value-added products if selective electrocatalysts and integrated devices were developed. Here we identify a mechanistic route to selectively producing either CO or CH4 with high selectivity (>95%) using Ir–ceria-based catalysts in an intermediate-temperature (400 °C) CO2 electrolyser that operates at low overpotential and ambient pressure. We show that tuning of the Ir–O hybridization by controlling the Ir speciation can alter the catalyst surface chemical environment, enabling the stabilization of specific transition states for the production of either CO or CH4 during electrocatalysis. By achieving CO2 electrohydrogenation in tandem with light-alkane electrodehydrogenation, we further demonstrate that such an advanced electrolyser could be extended to the upgrade of different carbon resources in one-step, significantly enhancing the techno-economic feasibilty of the process. Coupled thermal–electrochemical catalysis offers an attractive approach to upgrading CO2 into value-added products. Now, Ir–ceria-based catalysts in a protonic ceramic CO2 electrolyser are shown to selectively produce either CO or CH4 by tuning the Ir–O orbital hybridization.

A comprehensive measurement of planetary boundary layer (PBL) meteorology was conducted at 140 and 280 m on a meteorological tower in Beijing, China, to quantify the effect of aerosols on radiation and its role in PBL development. The measured variables included four-component radiation, temperature, sensible heat flux (SH), and turbulent kinetic energy (TKE) at 140 and 280 m, as well as PBL height (PBLH). In this work, a method was developed to quantitatively estimate the effect of aerosols on radiation based on the PBLH and radiation at the two heights (140 and 280 m). The results confirmed that the weakened downward shortwave radiation (DSR) on hazy days could be attributed predominantly to increased aerosols, while for longwave radiation, aerosols only accounted for around one-third of the enhanced downward longwave radiation. The DSR decreased by 55.2 W m−2 on hazy days during noontime (1100–1400 local time). The weakened solar radiation decreased SH and TKE by enhancing atmospheric stability, and hence suppressed PBL development. Compared with clean days, the decreasing rates of DSR, SH, TKE, and PBLH were 11.4%, 33.6%, 73.8%, and 53.4%, respectively. These observations collectively suggest that aerosol radiative forcing on the PBL is exaggerated by a complex chain of interactions among thermodynamic, dynamic, and radiative processes. These findings shed new light on our understanding of the complex relationship between aerosol and the PBL.

By increasing the charging voltage, a cell specific energy of >400 W h kg−1 is achievable with LiNi0.8Mn0.1Co0.1O2 in Li metal batteries. However, stable cycling of high-nickel cathodes at ultra-high voltages is extremely challenging. Here we report that a rationally designed sulfonamide-based electrolyte enables stable cycling of commercial LiNi0.8Co0.1Mn0.1O2 with a cut-off voltage up to 4.7 V in Li metal batteries. In contrast to commercial carbonate electrolytes, the electrolyte not only suppresses side reactions, stress-corrosion cracking, transition-metal dissolution and impedance growth on the cathode side, but also enables highly reversible Li metal stripping and plating leading to a compact morphology and low pulverization. Our lithium-metal battery delivers a specific capacity >230 mA h g−1 and an average Coulombic efficiency >99.65% over 100 cycles. Even under harsh testing conditions, the 4.7 V lithium-metal battery can retain >88% capacity for 90 cycles, advancing practical lithium-metal batteries. Charging at high voltages in principle makes batteries energy dense, but this is often achieved at the cost of the cycling stability. Here the authors design a sulfonamide-based electrolyte to enable a Li metal battery with a state-of-the-art cathode at an ultra-high voltage of 4.7 V while maintaining cyclability.