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Importance: African swine fever (ASF) caused by ASF virus (ASFV) is a highly contagious and acute hemorrhagic viral disease in domestic pigs. Until now, no effective commercial vaccine and antiviral drugs are available for ASF control. Here, we generated a new live-attenuated vaccine candidate (ASFV-ΔH240R-Δ7R) by deleting H240R and MGF505-7R genes from the highly pathogenic ASFV HLJ/18 genome. Piglets immunized with ASFV-ΔH240R-Δ7R were safe without any ASF-related signs and produced specific antibodies against p30. Challenged with a virulent ASFV HLJ/18, the piglets immunized with high-dose group (105 HAD50) exhibited 100% protection without clinical symptoms, showing that low levels of virus replication with no observed pathogenicity by postmortem and histological analysis. Overall, our results provided a new strategy by designing live-attenuated vaccine candidate, resulting in protection against ASFV infection., Competing Interests: The authors declare no conflict of interest.

Purpose: This large, single-center, retrospective cohort study was aimed to explore the effect of female body mass index (BMI) on ectopic pregnancy (EP) following fresh and frozen-thawed embryo transfers (ET)., Methods: A total of 27,600 pregnancies after fresh ET and 14,762 pregnancies after frozen-thawed ET were included between January 2010 to June 2022. Women were divided into three groups based on BMI according to the Working Group on Obesity in China (WGOC), International Life Sciences Institute (ILSI): underweight (BMI < 18.5 kg/m 2 ), normal weight (BMI, 18.5-23.9 kg/m 2 ), and overweight or obesity (≥ 24 kg/m 2 ). Compare EP rates among BMI categories in fresh and frozen-thawed ET cycles respectively. Multivariate logistic regression analyses were used to investigate the association between female BMI and EP., Results: The overall EP rates in fresh, and frozen thawed transfer cycles were 2.43% (672/27,600) and 2.82% (417/14,762), respectively. In fresh ET cycles, underweight women yielded a significantly higher EP rate than those with normal and excess weight (3.29% vs. 2.29% vs. 2.54%, P = 0.029). But EP rates did not differ among the three BMI groups (2.72% vs. 2.76% vs. 2.96%, P = 0.782) in frozen-thawed ET cycles. In fresh ET cycles, after adjusting for potential confounding factors, no significant association was found between female BMI and EP occurrence (adjusted OR: 0.98, 95% CI 0.70-1.37, P = 0.894, for BMI 18.5-23.9 kg/m 2 ; adjusted OR: 0.89, 95% CI 0.75-1.06, P = 0.205, for BMI ≥ 24 kg/m 2 . Reference = BMI < 18.5 kg/m 2 )., Conclusion(s): Female BMI did not affect the occurrence of ectopic pregnancy in either fresh or frozen-thawed embryo transfer cycles., (© 2023. The Author(s).)

To clarify the reasons for inaccurate fire detection in aircraft cargo holds, this article depicts research from the perspective of a single type of sensor detection. In terms of fire smoke, we select dual-wavelength photoelectric smoke sensors for fire-data collection and a genetic algorithm to optimize the classification and detection of random forest fires. From the perspective of fire CO concentration, we use PSO-LSTM to train a CO concentration compensation model to reduce sensor measurement errors. Research is then conducted from the perspective of various types of sensor detection, using the improved BP-AdaBoost algorithm to train a fire-detection model and achieve the high-precision identification of complex environments and fire situations.

Aims: This work was designed to provide early diagnosis strategies for Alzheimer's disease (AD) based on the identification of blood metabolic biomarkers. Patients & methods: A total of 90 subjects aged 60 years or older were included in this study; 45 patients were assigned to the case group and control group, respectively. A total of 31 target metabolites were quantitatively analyzed by parallel reaction monitoring between the two groups. Results & conclusion: Three metabolites were screened out, including cystine, serine and alanine/sarcosine. Logistic regression and random forest analysis were used to establish AD diagnosis models, and the model combining metabolic biomarkers and demographic variables had higher detection efficiency (area under the curve = 0.869). A combination diagnostic model to provide a scientific reference for early screening and diagnosis of AD was constructed.

Background: Post-stroke cognitive impairment (PSCI) is one of the serious complications of stroke. The Montreal Cognitive Assessment (MoCA), as a brief cognitive impairment screening tool, is widely used in stroke survivors. However, some studies have suggested that the use of the universal cutoff value of 26 may be inappropriate for detecting cognitive impairments in stroke settings., Aim: We conducted this study to identify the optimal cutoff value of the MoCA in screening for PSCI., Methods: PubMed, CINAHL, Embase, the Cochrane Library, and Web of Science were searched for eligible studies until March 23, 2023. All studies were screened by two independent researchers. The quality of each article was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate mixed-effects model was used to pool sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the summary receiver operating characteristic curve., Results: Twenty-four studies with a total of 4231 patients were included in this review. Despite the lack of evidence of publication bias, a high degree of heterogeneity was observed. A meta-analysis revealed that a cutoff value of 21/22 yielded the best diagnostic accuracy. The optimal cutoff varied in different regions, stroke types, and stroke phases as well., Conclusion: The optimal cutoff of MoCA was 21/22 for stroke populations rather than the initially recommended cutoff of 26. A revised (lower) cutoff should be considered for stroke survivors.

African swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease in domestic pigs and wild boars. Domestic pigs infected with virulent African swine fever virus (ASFV) isolates have a high mortality, approaching 100%. Identification of ASFV genes related to virulence/pathogenicity and deletion of them are considered to be key steps in the development of live attenuated vaccines, because the ability of ASFV to escape host innate immune responses is related to viral pathogenicity. However, the relationship between the host antiviral innate immune responses and the pathogenic genes of ASFV has not been fully understood. In this study, the ASFV H240R protein (pH240R), a capsid protein of ASFV, was found to inhibit type I interferon (IFN) production. Mechanistically, pH240R interacted with the N-terminal transmembrane domain of stimulator of interferon genes (STING) and inhibited its oligomerization and translocation from the endoplasmic reticulum to the Golgi apparatus. Additionally, pH240R inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and TANK binding kinase 1 (TBK1), leading to reduced production of type I IFN. Consistent with these results, infection with H240R -deficient ASFV (ASFV-ΔH240R) induced more type I IFN than infection with its parental strain, ASFV HLJ/18. We also found that pH240R may enhance viral replication via inhibition of type I IFN production and the antiviral effect of interferon alpha (IFN-α). Taken together, our findings provide a new explanation for the reduction of ASFV's replication ability by knockout of the H240R gene and a clue for the development of live attenuated ASFV vaccines. IMPORTANCE African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious and acute hemorrhagic viral disease with a high mortality, approaching 100% in domestic pigs. However, the relationship between viral pathogenicity and immune evasion of ASFV is not fully understood, which limits the development of safe and effective ASF vaccines, specifically, live attenuated vaccines. In this study, we found that pH240R, as a potent antagonist, inhibited type I IFN production by targeting STING and inhibiting its oligomerization and translocation from the endoplasmic reticulum to the Golgi apparatus. Furthermore, we also found that deletion of the H240R gene reduced viral pathogenicity by enhancing type I IFN production, which decreases ASFV replication. Taken together, our findings provide a clue for the development of an ASFV live attenuated vaccine via deleting the H240R gene., Competing Interests: The authors declare no conflict of interest.

Access Control Policies (ACPs) are essential for ensuring secure and authorized access to resources in IoT networks. Recognizing these policies involves identifying relevant statements within project documents expressed in natural language. While current research focuses on improving recognition accuracy through algorithm enhancements, the challenge of limited labeled data from individual clients is often overlooked, which impedes the training of highly accurate models. To address this issue and harness the potential of IoT networks, this paper presents FL-Bert-BiLSTM, a novel model that combines federated learning and pre-trained word embedding techniques for access control policy recognition. By leveraging the capabilities of IoT networks, the proposed model enables real-time and distributed training on IoT devices, effectively mitigating the scarcity of labeled data and enhancing accessibility for IoT applications. Additionally, the model incorporates pre-trained word embeddings to leverage the semantic information embedded in textual data, resulting in improved accuracy for access control policy recognition. Experimental results substantiate that the proposed model not only enhances accuracy and generalization capability but also preserves data privacy, making it well-suited for secure and efficient access control in IoT networks.

Multi-wavelength Raman lidar has been widely used in profiling aerosol optical properties. The accuracy of measured aerosol optical properties largely depends on sophisticated lidar data retrieval algorithms. Commonly to retrieve aerosol optical properties of Raman lidar, the extinction-related Ångström exponent (EAE) is assumed (to be 1). This value usually generally differs from the true value (called EAE deviation) and adds uncertainty to the retrieved aerosol optical properties. Lidar-signal noise and EAE-deviation are two important error sources for retrieving aerosol optical properties. As the measurement accuracy of Raman lidar has been greatly improved in recent years, the influence of signal noise on retrieval results becomes relatively small, and the uncertainty of retrieved aerosol optical properties caused by an EAE-deviation becomes nonnegligible, especially in scenes that EAE deviation is large. In this study, an iteration retrieval algorithm is proposed to obtain more reliable EAE based on multi-wavelength Raman lidar. Results from this iteration are more precise values of aerosol optical properties. Three atmospheric scenarios where aerosol distribution and the values of EAE vary widely were simulated with a Monte Carlo method to analyze the characteristics and robustness of the iterative algorithm. The results show that the proposed iterative algorithm can eliminate the systematic errors of aerosol optical properties retrieved by traditional retrieval method. The EAEs after iteration does converge to the true value, and the accuracy of aerosol optical properties can be greatly improved, especially for the particle backscatter coefficient and lidar ratio, which has been improved by more than 10% in most cases, and even more than 30%. In addition, field observations data of a three-wavelength Raman lidar are analyzed to illustrate the necessity and reliability of the proposed iterative retrieval algorithm.

A good response to neoadjuvant chemotherapy (NACT) is strongly associated with a higher curative resection rate and favorable outcomes for patients with gastric cancer (GC). We examined the utility of serial circulating tumor DNA (ctDNA) testing for monitoring NACT response and prognosis in stage II-III GC. Seventy-nine patients were enrolled to receive two cycles of NACT following gastrectomy with D2-lymphadenectomy. Plasma at baseline, post-NACT, and after surgery, and tissue at pretreatment and surgery were collected. We used a 425-gene panel to detect genomic alterations (GAs). Results show that the mean cell-free DNA concentration of patients with clinical stage III was significantly higher than patients with stage II (15.43 ng·mL -1 vs 14.40 ng·mL -1 ). After receiving NACT and surgery, the overall detection rate of ctDNA gradually reduced (59.5%, 50.8%, and 47.4% for baseline, post-NACT, and postsurgery). The maximum variant allele frequency (max-VAF) and the number of GAs decreased from 0.50% to 0.08% and from 2.9 to 1.7 after NACT. For patients with a partial response after NACT, the max-VAF and the number of GAs declined significantly, but they increased for patients with progressive disease. Patients with detectable ctDNA at baseline, after NACT, or after surgery have a worse overall survival (OS) than patients with undetectable ctDNA. The estimated 3-year OS was 73% for the post-NACT ctDNA-negative patients and 34% for ctDNA-positive. Patients with perpetual negative ctDNA before and after NACT have the best prognosis. In conclusion, ctDNA was proposed as a potential biomarker to predict prognosis and monitor the NACT response for stage II-III GC patients., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Electronic health records (EHRs) offer great promises for advancing precision medicine and, at the same time, present significant analytical challenges. Particularly, it is often the case that patient-level data in EHRs cannot be shared across institutions (data sources) due to government regulations and/or institutional policies. As a result, there are growing interests about distributed learning over multiple EHRs databases without sharing patient-level data. To tackle such challenges, we propose a novel communication efficient method that aggregates the optimal estimates of external sites, by turning the problem into a missing data problem. In addition, we propose incorporating posterior samples of remote sites, which can provide partial information on the missing quantities and improve efficiency of parameter estimates while having the differential privacy property and thus reducing the risk of information leaking. The proposed approach, without sharing the raw patient level data, allows for proper statistical inference. We provide theoretical investigation for the asymptotic properties of the proposed method for statistical inference as well as differential privacy, and evaluate its performance in simulations and real data analyses in comparison with several recently developed methods., (© 2022 The International Biometric Society.)

Since the first laparoscopic radical surgery for early gastric cancer 30 years ago, there has been a gradual shift from "open" to "minimally invasive" surgery for gastric cancer. This transition is due to advancements in refined anatomy, enlarged field of view, faster recovery, and comparable oncological outcomes. Several high-quality clinical studies have demonstrated the safety and effectiveness of laparoscopy in the treatment of both early and locally advanced gastric cancer. The role of perioperative chemotherapy in managing locally advanced gastric cancer has been widely recognized, and there have been continuous breakthroughs in the exploration of targeted therapy and immunotherapy for perioperative treatment. Additionally, the application of indocyanine green near-infrared imaging technology, 3D laparoscopic technology, and robotic surgery systems has further improved the accuracy and minimally invasive nature of gastric cancer surgeries. Looking ahead, the field of minimally invasive surgery for gastric cancer is expected to become more standardized, resulting in a significant enhancement in the quality of life for gastric cancer patients., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Background: The relationship between endometrial thickness and pregnancy safety after in vitro fertilization treatment is an important topic that should provoke attention. The aim of this study was to demonstrate the relationship between endometrial thickness on day of embryo transfer and early pregnancy complications, including ectopic pregnancy and early miscarriage, in frozen thawed embryo transfer (FET) cycles., Methods: Patients undergoing their first FET cycles were included into this study from January 2010 to December 2021. Patients were divided into three groups according to endometrial thickness on day of embryo transfer: Thin, ≤ 7 mm; Medium, 7-14 mm; Thick, ≥ 14 mm. Ectopic pregnancy and early miscarriage were the two primary outcomes. Endometrial thickness was the main measured variable. The risk factors of these two compilations were determined based on univariate analysis and multivariate logistic regression analysis., Results: A total of 11138 clinical pregnancies were included. The overall ectopic pregnancy and early spontaneous miscarriage rates were 2.62% and 13.40%. The ectopic pregnancy and early spontaneous miscarriage rates were significantly higher in patients with thin endometrium as compared with those in the other two groups (ectopic pregnancy rate: 5.06% vs. 2.62% vs. 1.05%; P < 0.001; early spontaneous miscarriage rate: 15.18% vs. 13.45% vs. 11.53%; P < 0.001). In multivariate logistic regression analysis, thin endometrium was an independent factor to predict ectopic pregnancy [adjusted odds ratio (aOR): 5.62; 95% confidence interval (CI): 2.51-12.58, P < 0.001], and to predict early spontaneous miscarriage rate (aOR: 1.57; 95% CI: 1.21-1.74, P < 0.001)., Conclusion: Thin endometrium on day of embryo transfer in FET cycles is an independent predictor for early pregnancy compilations, including ectopic pregnancy and early spontaneous miscarriage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Song, Bu and Sun.)

Research Question: Does polycystic ovary syndrome (PCOS) independently influence the risk of early spontaneous miscarriage in patients undergoing single euploid vitrified blastocyst transfer?, Design: This observational cohort study retrospectively analysed 1498 patients undergoing their first single euploid blastocyst frozen transfer cycles between October 2016 and December 2021. Patients were divided into PCOS and non-PCOS groups according to the Rotterdam criteria. Logistic regression analysis was conducted to study the independent effect of maternal PCOS status on early spontaneous miscarriage after single euploid embryo transfer after adjusting for confounding factors., Results: No statistically significant differences were identified in the rates of positive pregnancy test (68.95% versus 64.86%, P = 0.196) or clinical pregnancy (59.93% versus 57.33%, P = 0.429) between the PCOS and non-PCOS groups after single euploid embryo transfer. Early spontaneous miscarriage occurred more frequently in women with PCOS compared with controls (18.67% versus 12.00%, P = 0.023). In single euploid embryo transfer cycles, PCOS significantly increased the incidence of early spontaneous miscarriage after adjusting for some potential confounders (adjusted odds ratio 1.649, 95% CI 1.032 to 2.635, P = 0.036)., Conclusions: Although no significant difference was observed in clinical pregnancy rates, PCOS status increased the risk of early spontaneous miscarriage after single vitrified euploid blastocyst transfer, suggesting an additional role of endometrial dysfunction affected by endocrine disorders. Further studies are needed to investigate the specific mechanisms and effective intervention strategies., (Copyright © 2023 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Abnormal epigenetic regulation is identified to correlate with cancer progression and renders tumor refractory and resistant to reactive oxygen species (ROS)-based anti-tumor actions. To address it, a sequential ubiquitination and phosphorylation epigenetics modulation strategy is developed and exemplified by the well-established Fe-metal-organic framework (Fe-MOF)-based chemodynamic therapy (CDT) nanoplatforms that load the 26S proteasome inhibitor (i.e., MG132). The encapsulated MG132 can blockade 26S proteasome, terminate ubiquitination, and further inhibit transcription factor phosphorylation (e.g., NF-κB p65), which can boost pro-apoptotic or misfolded protein accumulations, disrupt tumor homeostasis, and down-regulate driving genes expression of metastatic colorectal cancer (mCRC). Contributed by them, Fe-MOF-unlocked CDT is magnified to considerably elevate ROS content for repulsing mCRC, especially after combining with macrophage membrane coating-enabled tropism accumulation. Systematic experiments reveal the mechanism and signaling pathway of such a sequential ubiquitination and phosphorylation epigenetics modulation and explain how it could blockade ubiquitination and phosphorylation to liberate the therapy resistance to ROS and activate NF-κB-related acute immune responses. This unprecedented sequential epigenetics modulation lays a solid foundation to magnify oxidative stress and can serve as a general method to enhance other ROS-based anti-tumor methods., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Cytoplasmic stress granules (SGs) are generally triggered by stress-induced translation arrest for storing mRNAs. Recently, it has been shown that SGs are regulated by different stimulators including viral infection, which is involved in the antiviral activity of host cells to limit viral propagation. To survive, several viruses have been reported to execute various strategies, such as modulating SG formation, to create optimal surroundings for viral replication. African swine fever virus (ASFV) is one of the most notorious pathogens in the global pig industry. However, the interplay between ASFV infection and SG formation remains largely unknown. In this study, we found that ASFV infection inhibited SG formation. Through SG inhibitory screening, we found that several ASFV-encoded proteins are involved in inhibition of SG formation. Among them, an ASFV S273R protein (pS273R), the only cysteine protease encoded by the ASFV genome, significantly affected SG formation. ASFV pS273R interacted with G3BP1 (Ras-GTPase-activating protein [SH3 domain] binding protein 1), a vital nucleating protein of SG formation. Furthermore, we found that ASFV pS273R cleaved G3BP1 at the G140-F141 to produce two fragments (G3BP1-N 1-140 and G3BP1-C 141-456 ). Interestingly, both the pS273R-cleaved fragments of G3BP1 lost the ability to induce SG formation and antiviral activity. Taken together, our finding reveals that the proteolytic cleavage of G3BP1 by ASFV pS273R is a novel mechanism by which ASFV counteracts host stress and innate antiviral responses., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. The funding source was not involved in the analysis or the preparation of this report. The corresponding authors had full access to all the data and accepted the final responsibility for the decision to submit this article for publication., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The cell-cell adhesion cadherin-catenin complexes recruit vinculin to the adherens junction (AJ) to modulate the mechanical couplings between neighboring cells. However, it is unclear how vinculin influences the AJ structure and function. Here, we identified two patches of salt bridges that lock vinculin in the head-tail autoinhibited conformation and reconstituted the full-length vinculin activation mimetics bound to the cadherin-catenin complex. The cadherin-catenin-vinculin complex contains multiple disordered linkers and is highly dynamic, which poses a challenge for structural studies. We determined the ensemble conformation of this complex using small-angle x-ray and selective deuteration/contrast variation small-angle neutron scattering. In the complex, both α-catenin and vinculin adopt an ensemble of flexible conformations, but vinculin has fully open conformations with the vinculin head and actin-binding tail domains well separated from each other. F-actin binding experiments show that the cadherin-catenin-vinculin complex binds and bundles F-actin. However, when the vinculin actin-binding domain is removed from the complex, only a minor fraction of the complex binds to F-actin. The results show that the dynamic cadherin-catenin-vinculin complex employs vinculin as the primary F-actin binding mode to strengthen AJ-cytoskeleton interactions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Background: The objective of this study was to explore whether the duration of LFEP (late-follicular elevated progesterone) affected pregnancy outcomes in IVF ( in vitro fertilization) patients treated with pituitary downregulation protocols., Method: Patients with their first IVF/ICSI cycles between January 2016 and December 2016 were included. LFEP was set either at P > 1.0ng/ml or P > 1.5ng/ml. Clinical pregnancy rate was compared among three different groups (no LFEP; LFEP for 1 day; LFEP for ≥ 2 days). Then multivariate logistic regression analysis was performed to explore the influencing factors of clinical pregnancy rate., Results: This retrospective analysis involved 3,521 first IVF/ICSI cycles with fresh embryo transfers. Clinical pregnancy rate was the lowest in patients with a LFEP duration of ≥ 2 days, irrespective of whether LFEP was defined as P > 1.0 ng/ml (68.79% vs. 63.02% vs. 56.20%; P = 0.000) or as P > 1.5 ng/ml (67.24% vs. 55.95% vs. 45.51%; P = 0.000). In addition, LFEP duration was significantly associated with clinical pregnancy outcomes in unadjusted logistic regression analysis. However, in multivariate regression models after adjusting confounders, adjusted OR for LFEP duration (≥ 2 days) in the two models was 0.808 ( P = 0.064; LFEP as P > 1.0 ng/ml) and 0.720 ( P = 0.098; LFEP as P > 1.5 ng/ml), respectively., Conclusion: LFEP adversely affects clinical pregnancy outcomes. However, the duration of LFEP seems to have no influence on the clinical pregnancy rate in pituitary downregulation treatment cycles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Ge and Bu.)

Endophytes play an important role in shaping plant growth and immunity. However, the mechanisms for endophyte-induced disease resistance in host plants remain unclear. Here, we screened and isolated the immunity inducer ShAM1 from the endophyte Streptomyces hygroscopicus OsiSh-2, which strongly antagonizes the pathogen Magnaporthe oryzae. Recombinant ShAM1 can trigger rice immune responses and induce hypersensitive responses in various plant species. After infection with M. oryzae, blast resistance was dramatically improved in ShAM1-inoculated rice. In addition, the enhanced disease resistance by ShAM1 was found to occur through a priming strategy and was mainly regulated through the jasmonic acid-ethylene (JA/ET)-dependent signaling pathway. ShAM1 was identified as a novel α-mannosidase, and its induction of immunity is dependent on its enzyme activity. When we incubated ShAM1 with isolated rice cell walls, the release of oligosaccharides was observed. Notably, extracts from the ShAM1-digested cell wall can enhance the disease resistance of the host rice. These results indicated that ShAM1 triggered immune defense against pathogens by damage-associated molecular pattern (DAMP)-related mechanisms. Our work provides a representative example of endophyte-mediated modulation of disease resistance in host plants. The effects of ShAM1 indicate the promise of using active components from endophytes as plant defense elicitors for the management of plant disease. IMPORTANCE The specific biological niche inside host plants allows endophytes to regulate plant disease resistance effectively. However, there have been few reports on the role of active metabolites from endophytes in inducing host disease resistance. In this study, we demonstrated that an identified α-mannosidase protein, ShAM1, secreted by the endophyte S. hygroscopicus OsiSh-2 could activate typical plant immunity responses and induce a timely and cost-efficient priming defense against the pathogen M. oryzae in rice. Importantly, we revealed that ShAM1 enhanced plant disease resistance through its hydrolytic enzyme (HE) activity to digest the rice cell wall and release damage-associated molecular patterns. Taken together, these findings provide an example of the interaction mode of endophyte-plant symbionts and suggest that HEs derived from endophytes can be used as environmentally friendly and safe prevention agent for plant disease control., Competing Interests: The authors declare no conflict of interest.

Insect gut microbiota have been widely reported to help the insects to overcome host tree defense. Streltzoviella insularis (Lepidoptera: Cossidae) is one of the most common wood borers in China, attacking various hosts, including ash trees ( Fraxinus sp.), but little is known about its gut microbial associates and their involvement in host tree defense. We isolated gut bacteria of S. insularis larvae, analyzed their ability to degrade pinoresinol (a defense compound of ash trees) and cellulose, and identified pinoresinol degradation products. Larval mortality increased with increasing pinoresinol concentration (reflecting natural variation observed in the host trees). All the five detected gut bacteria isolates were able to degrade pinoresinol, two of which were also capable of cellulose degradation. Furthermore, gut bacteria were also shown to degrade pinoresinol via the gluconeogenesis pathway. These results suggest that S. insularis -associated microorganisms help to overcome host pinoresinol defense and possibly contribute to insects or gut microbial nutrition via carbohydrate synthesis.

Differentially private (DP) training preserves the data privacy usually at the cost of slower convergence (and thus lower accuracy), as well as more severe mis-calibration than its non-private counterpart. To analyze the convergence of DP training, we formulate a continuous time analysis through the lens of neural tangent kernel (NTK), which characterizes the per-sample gradient clipping and the noise addition in DP training, for arbitrary network architectures and loss functions. Interestingly, we show that the noise addition only affects the privacy risk but not the convergence or calibration, whereas the per-sample gradient clipping (under both flat and layerwise clipping styles) only affects the convergence and calibration. Furthermore, we observe that while DP models trained with small clipping norm usually achieve the best accurate, but are poorly calibrated and thus unreliable. In sharp contrast, DP models trained with large clipping norm enjoy the same privacy guarantee and similar accuracy, but are significantly more calibrated . Our code can be found at https://github.com/woodyx218/opacus&#95;global&#95;clipping.

The rheological properties and microstructure of doughs, and the texture properties of whole wheat breads and noodles were investigated. The gluten strength of doughs were discriminated due to wheat cultivar. Reduced flour particle size led to the doughs with a stronger gluten strength (i.e., smaller C2), lower degree of starch retrogradation (i.e., smaller C5), and longer relaxation time (i.e., larger n values). Firmer crumb of breads were prepared by flours with smaller particle size. With increased bran content, the gluten strength of dough weakened (i.e., increased C2), the development and relaxation time of dough and the degree of starch retrogradation decreased (i.e., decreased C1 time, n values and C5), the dough structure became more porous, and the product texture appeared to be firmer. As such, outcomes from this research will provide a practical guidance for the bakery industry to improve the consumer acceptability of whole wheat products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

African swine fever virus (ASFV) poses a great threat to the global pig industry and food security. Currently, 24 ASFV genotypes have been reported but it is unclear whether recombination of different genotype viruses occurs in nature. In this study, we detect three recombinants of genotype I and II ASFVs in pigs in China. These recombinants are genetically similar and classified as genotype I according to their B646L gene, yet 10 discrete fragments accounting for over 56% of their genomes are derived from genotype II virus. Animal studies with one of the recombinant viruses indicate high lethality and transmissibility in pigs, and deletion of the virulence-related genes MGF&#95;505/360 and EP402R derived from virulent genotype II virus highly attenuates its virulence. The live attenuated vaccine derived from genotype II ASFV is not protective against challenge of the recombinant virus. These naturally occurring recombinants of genotype I and II ASFVs have the potential to pose a challenge to the global pig industry., (© 2023. The Author(s).)

Due to rising living standards, it is important to improve wheat's quality traits by adjusting its storage protein genes. The introduction or locus deletion of high molecular weight subunits could provide new options for improving wheat quality and food safety. In this study, digenic and trigenic wheat lines were identified, in which the 1Dx5+1Dy10 subunit, and NGli-D2 and Sec-1 s genes were successfully polymerized to determine the role of gene pyramiding in wheat quality. In addition, the effects of ω-rye alkaloids during 1BL/1RS translocation on quality were eliminated by introducing and utilizing 1Dx5+1Dy10 subunits through gene pyramiding. Additionally, the content of alcohol-soluble proteins was reduced, the Glu/Gli ratio was increased and high-quality wheat lines were obtained. The sedimentation values and mixograph parameters of the gene pyramids under different genetic backgrounds were significantly increased. Among all the pyramids, the trigenic lines in Zhengmai 7698, which was the genetic background, had the highest sedimentation value. The mixograph parameters of the midline peak time (MPT), midline peak value (MPV), midline peak width (MPW), curve tail value (CTV), curve tail width (CTW), midline value at 8 min (MTxV), midline width at 8 min (MTxW) and midline integral at 8 min (MTxI) of the gene pyramids were markedly enhanced, especially in the trigenic lines. Therefore, the pyramiding processes of the 1Dx5+1Dy10 , Sec-1 S and NGli-D2 genes improved dough elasticity. The overall protein composition of the modified gene pyramids was better than that of the wild type. The Glu/Gli ratios of the type I digenic line and trigenic lines containing the NGli-D2 locus were higher than that of the type II digenic line without the NGli-D2 locus. The trigenic lines with Hengguan 35 as the genetic background had the highest Glu/Gli ratio among the specimens. The unextractable polymeric protein (UPP%) and Glu/Gli ratios of the type II digenic line and trigenic lines were significantly higher than those of the wild type. The UPP% of the type II digenic line was higher than that of the trigenic lines, while the Glu/Gli ratio was slightly lower than that of the trigenic lines. In addition, the celiac disease (CD) epitopes' level of the gene pyramids significantly decreased. The strategy and information reported in this study could be very useful for improving wheat processing quality and reducing wheat CD epitopes.

Mapping tumor metabolic remodeling and their spatial crosstalk with surrounding non-tumor cells can fundamentally improve our understanding of tumor biology, facilitates the designing of advanced therapeutic strategies. Here, we present an integration of mass spectrometry imaging-based spatial metabolomics and lipidomics with microarray-based spatial transcriptomics to hierarchically visualize the intratumor metabolic heterogeneity and cell metabolic interactions in same gastric cancer sample. Tumor-associated metabolic reprogramming is imaged at metabolic-transcriptional levels, and maker metabolites, lipids, genes are connected in metabolic pathways and colocalized in the heterogeneous cancer tissues. Integrated data from spatial multi-omics approaches coherently identify cell types and distributions within the complex tumor microenvironment, and an immune cell-dominated "tumor-normal interface" region where tumor cells contact adjacent tissues are characterized with distinct transcriptional signatures and significant immunometabolic alterations. Our approach for mapping tissue molecular architecture provides highly integrated picture of intratumor heterogeneity, and transform the understanding of cancer metabolism at systemic level., (© 2023. The Author(s).)

African swine fever is a fatal infectious disease caused by African swine fever virus (ASFV). The high mortality caused by this infectious disease is a significant challenge to the swine industry worldwide. ASFV virulence is related to its ability to antagonize IFN response, yet the mechanism of antagonism is not understood. Recently, a less virulent recombinant virus has emerged that has a EP402R gene deletion within the parental ASFV HLJ/18 (ASFV-ΔEP402R) strain. EP402R gene encodes CD2v. Hence we hypothesized that ASFV uses CD2v protein to evade type I IFN-mediated innate immune response. We found that ASFV-ΔEP402R infection induced higher type I IFN response and increased the expression of IFN-stimulated genes in porcine alveolar macrophages when compared with parental ASFV HLJ/18. Consistent with these results, CD2v overexpression inhibited type I IFN production and IFN-stimulated gene expression. Mechanistically, CD2v, by interacting with the transmembrane domain of stimulator of IFN genes (STING), prevented the transport of STING to the Golgi apparatus, and thereby inhibited the cGMP-AMP synthase-STING signaling pathway. Furthermore, ASFV CD2v disrupted IFNAR1-TYK2 and IFNAR2-JAK1 interactions, and thereby inhibited JAK-STAT activation by IFN-α. In vivo, specific pathogen-free pigs infected with the mutant ASFV-ΔEP402R strain survived better than animals infected with the parental ASFV HLJ/18 strain. Consistent with this finding, IFN-β protein levels in the peripheral blood of ASFV-ΔEP402R-challenged pigs were significantly higher than in the blood of ASFV HLJ/18-challenged pigs. Taken together, our findings suggest a molecular mechanism in which CD2v inhibits cGMP-AMP synthase-STING and IFN signaling pathways to evade the innate immune response rendering ASFV infection fatal in pigs., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Multiple imputation (MI) has been widely applied to missing value problems in biomedical, social and econometric research, in order to avoid improper inference in the downstream data analysis. In the presence of high-dimensional data, imputation models that include feature selection, especially ℓ 1 regularized regression (such as Lasso, adaptive Lasso, and Elastic Net), are common choices to prevent the model from underdetermination. However, conducting MI with feature selection is difficult: existing methods are often computationally inefficient and poor in performance. We propose MISNN, a novel and efficient algorithm that incorporates feature selection for MI. Leveraging the approximation power of neural networks, MISNN is a general and flexible framework, compatible with any feature selection method, any neural network architecture, high/low-dimensional data and general missing patterns. Through empirical experiments, MISNN has demonstrated great advantages over state-of-the-art imputation methods (e.g. Bayesian Lasso and matrix completion), in terms of imputation accuracy, statistical consistency and computation speed.

To evaluate the germplasm characteristics and nutritional value of Chinese native pigeon varieties, this study analyzed the nutrient composition of the meat of four Chinese native pigeon varieties and then compared them with those of the White King pigeon, which is the most commonly used in China. A total of 150 pigeons aged 28 d (squabs) of 5 breeds including Taihu pigeon, Shiqi pigeon, Ta-rim pigeon, Boot pigeon, and White King pigeon were selected for slaughter. The basic meat quality parameters and contents of conventional nutritional compositions, inosine acid, amino acids, and fatty acids were measured. The results showed that there were significant differences in flesh color ( L *, b *), pH, and water loss rate of different breeds of suckling pigeons ( p < 0.05). Compared with White King pigeons, four local breeds had dark breast meat and a low water loss rate. The protein contents of Taihu, Tarim, and Shiqi suckling pigeons were significantly higher than those of White King pigeons ( p < 0.05). Taihu pigeons had the highest protein content, reaching 22.72%. The inosinic acid content of Tarim pigeons was the highest (1.31 mg/g) and was significantly higher than that of Shiqi pigeons, Boot pigeons, and White King pigeons ( p < 0.05). There was no significant difference in the content of amino acids, the ratio of essential amino acids, and the ratio of umami amino acids in the meat of different breeds of pigeons ( p > 0.05). The percentage of saturated fatty acids (SFAs) in the breast muscle of local breeding pigeons was significantly lower than that of White King pigeons ( p < 0.05), and the percentages of lauric acid, palmitic acid, eicosanoic acid, and behenic acid in SFAs reached significant levels ( p < 0.05). The content of eicosapentaenoic acid (EPA) in the meat of Taihu pigeons was significantly higher than that in other breeds. In conclusion, compared with the White King pigeon, the meat of local breed pigeons (Taihu pigeon, Shiqi pigeon, Tarim pigeon, and Boot pigeon) had dark flesh, good water retention, high protein and inosine contents, a high proportion of essential amino acids, and a low saturated fatty acid ratio. In addition, Taihu pigeons had the highest protein content (22.72%), monounsaturated fatty acids (44.58%), and EPA (0.47%) compared to other breeds.

Some nanosystems based on carbon nanomaterials have been used for fluorescent chemical/biosensing, elementary information processing, and textual coding. However, little attention has been paid to utilizing biowaste-derived carbon nanomaterials for colorimetric multi-channel sensing and advanced molecular information protection (including text and pattern information). Herein, fish scale-derived carbon nanoparticles (FSCN) were prepared and used for colorimetric detection of metal ions, encoding, encrypting and hiding text- and pattern-based information. The morphology and composition of FSCN were analyzed by TEM, XRD, FTIR, and XPS, and it was found that the FSCN-based multi-channel colorimetric sensing system can detect Cr 6+ (detection limit of 56.59 nM and 13.32 nM) and Fe 3+ (detection limit of 81.55 nM) through the changes of absorption intensity at different wavelengths (272, 370, and 310 nm). Moreover, the selective responses of FSCN to 20 kinds of metal ions can be abstracted into a series of binary strings, which can encode, hide, and encrypt traditional text-based and even two-dimensional pattern-based information. The preparation of carbon nanomaterials derived from waste fish scales can stimulate other researcheres' enthusiasm for the development and utilization of wastes and promoting resource recycling. Inspired by this work, more researches will continue to explore the world of molecular information technology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Incomplete microwave ablation (iMWA) caused by uncontrollable heat diffusion enhances the immunosuppressive tumor microenvironment (ITM), consequently disabling the prevalent immune checkpoint blockade-combined immunotherapy against tumor recurrence. Herein, we successfully constructed an intratumorally synthesized Au bioreactor to disperse heat in thermally sensitive hydrogel-filled tumors and improve the energy utilization efficiency, which magnified the effective ablation zone (EAZ), counteracted iMWA, and simultaneously established and enhanced multiple biological process-regulated microwavegenetics. More significantly, we identified the extracellular matrix (ECM) viscosity as a general immune escape "target". After remodeling ECM, including ECM ingredients and cell adhesion molecules, this physical target was blocked by viscosity reprogramming, furnishing an effective tool to regulate the viscosity target. Thereby, such in situ Au bioreactor-enlarged EAZ and enhanced microwavegenetics reversed the immune-desert tumor microenvironment, mitigated ITM, secreted immune cell-attracting chemokines, recruited and polarized various immune cells, and activated or reactivated them like dendritic cells, natural killing cells, M1-type macrophages, and effector CD8+ or CAR-T cells. Contributed by these multiple actions, the in situ oncolytic Au bioreactors evoked CAR-T immunotherapy to acquire a considerably increased inhibition effect against tumor progression and recurrence after iMWA, thus providing a general method to enhance iMWA and CAR-T immunotherapy.

Object detection and recognition is a very important topic with significant research value. This research develops an optimised model of moving target identification based on CNN to address the issues of insufficient positioning information and low target detection accuracy (convolutional neural network). In this article, the target classification information and semantic location information are obtained through the fusion of the target detection model and the depth semantic segmentation model. The classification and position portion of the target detection model is provided by the simultaneous fusion of the image features carrying various information and a pyramid structure of multiscale image features so that the matched image fusion characteristics can be used by the target detection model to detect targets of various sizes and shapes. According to experimental findings, this method's accuracy rate is 0.941, which is 0.189 higher than that of the LSTM-NMS algorithm. Through the migration of CNN and the learning of context information, this technique has great robustness and enhances the scene adaptability of feature extraction as well as the accuracy of moving target position detection., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Zhe Yang et al.)

Objective: To assess whether progesterone (P) levels on the trigger day during preimplantation genetic testing (PGT) cycles are associated with embryo quality and pregnancy outcomes in the subsequent first frozen-thawed blastocyst transfer (FET) cycle., Methods: In this retrospective analysis, 504 eligible patients who underwent ICSI followed by frozen-thawed embryo transfer (FET) with preimplantation genetic test (PGT) between December 2014 and December 2019 were recruited. All patients adopted the same protocol, namely, the midluteal, short-acting, gonadotropin-releasing hormone agonist long protocol. The cutoff P values were 0.5 and 1.5 ng/ml when serum P was measured on the day of human chorionic gonadotropin (HCG) administration, and cycles were grouped according to P level on the day of HCG administration. Furthermore, the effect of trigger-day progesterone on embryo quality and the subsequent clinical outcome of FET in this PGT population was evaluated., Results: In total, 504 PGT cycles were analyzed. There was no significant difference in the number of euploid blastocysts, top-quality blastocysts, euploidy rate, or miscarriage rate among the three groups ( P >0.05). The 2PN fertilization rate (80.32% vs. 80.17% vs. 79.07%) and the top-quality blastocyst rate (8.71% vs. 8.24% vs. 7.94%) showed a downward trend with increasing P, and the between-group comparisons showed no significant differences ( P >0.05). The clinical pregnancy rate (41.25% vs. 64.79%; P <0.05) and live birth rate (35.00% vs. 54.93%; P <0.05) in subsequent FET cycles were substantially lower in the high-P group than in the P ≤ 0.5 ng/ml group. After adjustments were made for confounding variables, multivariate logistic regression analysis revealed that the high-P group had a lower clinical pregnancy rate (adjusted OR, 0.317; 95% CI, 0.145-0.692; P =0.004) and live birth rate (adjusted OR, 0.352; 95% CI, 0.160-0.773; P =0.009) than the low-P group in subsequent FET cycles, and the differences were significant., Conclusions: This study demonstrates that in the PGT population, elevated P on the trigger day may diminish the top-quality blastocyst rate (although there is no difference in the euploidy rate). Trigger-day P is an important factor influencing clinical outcomes in subsequent FET cycles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Cui, Shi, Bu, Wang, Sun and Zhang.)

Context: 46,XY, disorders of sexual development (46,XY, DSD) is a congenital genetic disease whose pathogenesis is complex and clinical manifestations are diverse. The existing molecular research has often focused on single-centre sequencing data, instead of prediction based on big data., Aims: This work aimed to fully understand the pathogenesis of 46,XY, DSD, and summarise the key pathogenic genes., Methods: Firstly, the potential pathogenic genes were identified from public data. Secondly, bioinformatics was used to predict pathogenic genes, including hub gene analysis, protein-protein interaction (PPI) and function enrichment analysis. Lastly, the genomic DNA from two unrelated families were recruited, next-generation sequencing and Sanger sequencing were performed to verify the hub genes., Key Results: A total of 161 potential pathogenic genes were selected from MGI and PubMed gene sets. The PPI network was built which included 144 nodes and 194 edges. MCODE 4 was selected from PPI which scored the most significant P -value. The top 15 hub genes were ranked and identified by Cytoscape. Furthermore, three variants were found on SRD5A2 gene by genome sequencing, which belonged to the prediction hub genes., Conclusions: Our results indicate that occurrence of 46,XY, DSD is attributed to a variety of genes. Bioinformatics analysis can help us predict the hub genes and find the most core network MCODE model., Implications: Bioinformatic predictions may provide a novel perspective on better understanding the pathogenesis of 46,XY, DSD.

Objective: The purpose of this study was to investigate the effect of body mass index (BMI) before treatment on the cumulative live birth rate (CLBR) over multiple complete in vitro fertilization (IVF) cycles in patients with polycystic ovary syndrome (PCOS)., Materials and Methods: This study is a single-center retrospective cohort study. It included 5016 patients with PCOS who started their first IVF cycle in our hospital between 2009 and 2018. Kaplan-Meier and log-rank tests were used for the comparison of CLBR across BMI groups. Univariate, multivariate models and stratification analysis were used to evaluate possible influencing factors of CLBR. Smoothing curve fitting was applied to present the correlation between BMI and CLBR. A one-line linear regression model was compared with a two-piecewise linear model using a log-likelihood ratio test., Results: During the 8-year follow-up, 3604 women (71.85%) obtained at least one live birth. The study population was grouped according to BMI, with BMI ranging from [14.53-23.00) kg/m 2 in the normal weight group, [23.00-27.50) kg/m 2 in the overweight group, and [27.50-37.80] kg/m 2 in the obese group, respectively. The CLBR of the obese group and the overweight group were significantly lower than the normal weight group. In the multivariate regression model, HR for CLBR was 0.86 [95%CI: 0.78-0.95] for the obese group, and 0.93 [0.86-1.00] for the overweight group, compared with the normal weight group as control. The curve fitting after adjustment for confounding factors and log-likelihood ratio test showed a one-line linear negative correlation between BMI and CLBR., Conclusion: We concluded that the BMI of PCOS patients had a negative one-line linear correlation with CLBR over multiple complete cycles., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

The facile and rapid fabrication of oriented porous polymers is crucial for flexible pressure sensors. Herein, a pressure sensor is developed based on oriented porous polydimethylsiloxane (PDMS) composites for detecting human motion and identifying joint motion patterns. The oriented porous PDMS composite is first constructed through thiol-ene click chemistry and directional freezing within only 30 min, then fabricated by interfacial in situ polymerization of dopamine and pyrrole to generate robust interfaces. As a result, the as-prepared oriented porous PDMS composite is assembled into a pressure sensor that shows potential applications in pressure and human motion detection. Interestingly, a sensor assembled by orthogonally stacking the PDMS composites can be used for joint motion pattern recognition with potential monitoring of football motion due to their directional structures. This facile strategy coupled with the oriented porous structure is expected to help design advanced wearable electronic devices., (© 2022 Wiley-VCH GmbH.)

Identification of bona fide functional receptors and elucidation of the mechanism of receptor-mediated virus entry are important to reveal targets for developing therapeutics against rabies virus (RABV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our previous studies suggest that metabotropic glutamate receptor subtype 2 (mGluR2) functions as an entry receptor for RABV in vitro , and is an important internalization factor for SARS-CoV-2 in vitro and in vivo . Here, we demonstrate that mGluR2 facilitates RABV internalization in vitro and infection in vivo . We found that transferrin receptor 1 (TfR1) interacts with mGluR2 and internalizes with mGluR2 and RABV in the same clathrin-coated pit. Knockdown of TfR1 blocks agonist-triggered internalization of mGluR2. Importantly, TfR1 also interacts with the SARS-CoV-2 spike protein and is important for SARS-CoV-2 internalization. Our findings identify a novel axis (mGluR2-TfR1 axis) used by RABV and SARS-CoV-2 for entry, and reveal TfR1 as a potential target for therapeutics against RABV and SARS-CoV-2. IMPORTANCE We previously found that metabotropic glutamate receptor subtype 2 (mGluR2) is an entry receptor for RABV in vitro , and an important internalization factor for SARS-CoV-2 in vitro and in vivo . However, whether mGluR2 is required for RABV infection in vivo was unknown. In addition, how mGluR2 mediates the internalization of RABV and SARS-CoV-2 needed to be resolved. Here, we found that mGluR2 gene knockout mice survived a lethal challenge with RABV. To our knowledge, mGluR2 is the first host factor to be definitively shown to play an important role in RABV street virus infection in vivo . We further found that transferrin receptor protein 1 (TfR1) directly interacts and cooperates with mGluR2 to regulate the endocytosis of RABV and SARS-CoV-2. Our study identifies a novel axis (mGluR2-TfR1 axis) used by RABV and SARS-CoV-2 for entry and opens a new door for the development of therapeutics against RABV and SARS-CoV-2.

Rabies virus (RABV) is a prototypical neurotropic virus that causes rabies in human and animals with an almost 100% mortality rate. Once RABV enters the central nervous system, no treatment is proven to prevent death. RABV glycoprotein (G) interacts with cell surface receptors and then enters cells via clathrin-mediated endocytosis (CME); however, the key host factors involved remain largely unknown. Here, we identified transferrin receptor 1 (TfR1), a classic receptor that undergoes CME, as an entry factor for RABV. TfR1 interacts with RABV G and is involved in the endocytosis of RABV. An antibody against TfR1 or the TfR1 ectodomain soluble protein significantly blocked RABV infection in HEK293 cells, N2a cells, and mouse primary neuronal cells. We further found that the endocytosis of TfR1 is coupled with the endocytosis of RABV and that TfR1 and RABV are transported to early and late endosomes. Our results suggest that RABV hijacks the transport pathway of TfR1 for entry, thereby deepening our understanding of the entry mechanism of RABV. IMPORTANCE For most viruses, cell entry involves engagement with many distinct plasma membrane components, each of which is essential. After binding to its specific receptor(s), rabies virus (RABV) enters host cells through the process of clathrin-mediated endocytosis. However, whether the receptor-dependent clathrin-mediated endocytosis of RABV requires other plasma membrane components remain largely unknown. Here, we demonstrate that transferrin receptor 1 (TfR1) is a functional entry factor for RABV infection. The endocytosis of RABV is coupled with the endocytosis of TfR1. Our results indicate that RABV hijacks the transport pathway of TfR1 for entry, which deepens our understanding of the entry mechanism of RABV.

African swine fever (ASF) is a highly contagious infectious disease of domestic pigs and wild boars caused by African swine fever virus (ASFV), with a mortality rate of up to 100%. In order to replicate efficiently in macrophages and monocytes, ASFV has evolved multiple strategies to evade host antiviral responses. However, the underlying molecular mechanisms by which ASFV-encoded proteins execute immune evasion are not fully understood. In this study, we found that ASFV pH240R strongly inhibits transcription, maturation, and secretion of interleukin-1β (IL-1β). Importantly, pH240R not only targeted NF-κB signaling but also impaired NLRP3 inflammasome activation. In this mechanism, pH240R interacted with NF-kappa-B essential modulator (NEMO), a component of inhibitor of kappa B kinase (IKK) complex and subsequently reduced phosphorylation of IκBα and p65. In addition, pH240R bonded to NLRP3 to inhibit NLRP3 inflammasome activation, resulting in reduced IL-1β production. As expected, infection with H240R -deficient ASFV (ASFV-ΔH240R) induced more inflammatory cytokine expression both in vitro and in vivo than its parental ASFV HLJ/18 strain. Consistently, H240R deficiency reduced the viral pathogenicity in pigs compared with its parental strain. These findings reveal that the H240R gene is an essential virulence factor, and deletion of the H240R gene affects the pathogenicity of ASFV HLJ/18 by enhancing antiviral inflammatory responses, which provides insights for ASFV immune evasion mechanisms and development of attenuated live vaccines and drugs for prevention and control of ASF. IMPORTANCE African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious and acute hemorrhagic viral disease of domestic pigs, with a high mortality approaching 100%. ASFV has spread rapidly worldwide and caused huge economic losses and ecological consequences. However, the pathogenesis and immune evasion mechanisms of ASFV are not fully understood, which limits the development of safe and effective ASF attenuated live vaccines. Therefore, investigations are urgently needed to identify virulence factors that are responsible for escaping the host antiviral innate immune responses and provide a new target for development of ASFV live-attenuated vaccine. In this study, we determined that the H240R gene is an essential virulence factor, and its depletion affects the pathogenicity of ASFV by enhancing NLRP3-mediated inflammatory responses, which provides theoretical support for the development of an ASFV attenuated live vaccine.

African Swine Fever (ASF) is a highly contagious and lethal pig disease and poses a huge threat to the pig industry worldwide. ASF virus (ASFV) encodes more than 150 different proteins, but the biological properties of most viral proteins are still unknown. ASFV CP312R protein has been proven to be one of the most immunogenic proteins during ASFV infection in pigs; however, its specific epitopes have yet to be identified. In this study, we verified the immunogenicity of CP312R protein in the sera from attenuated ASFV-inoculated pigs. We generated seven anti-ASFV CP312R mouse monoclonal antibodies (mAbs) from mice immunized with recombinant CP312R protein (rCP312R). All seven mAbs are the IgG2b-Kappa isotype and specifically interacted with the CP312R protein expressed in various cells that were infected by ASFVs or transfected with plasmid CP312R. The epitope mapping was performed by using these characterized mAbs and the peptide scanning (Pepscan) method followed by Western blot. As a result, two antigenic determinant regions were identified: two of the seven mAbs recognized the 122 KNEQGEEIYP 131 amino acids, and the remaining five mAbs recognized the 78 DEEVIRMNAE 87 amino acids of the CP312R protein. These antigenic determinants of CP312R are conserved in different ASFV strains of seven genotypes. By using the characterized mAb, confocal microscopy observation revealed that the CP312R was mainly localized in the cytoplasm and, to some extent, in nuclei and on the nuclear membrane of infected host cells. In summary, our results benefit our understanding on the antigenic regions of ASFV CP312R and help to develop better serological diagnosis of ASF and vaccine research.

Bile salt hydrolases are thought to be the gatekeepers of bile acid metabolism. To study the role of BSH in colitis, we investigated the ameliorative effects of different BSH-knockout strains of Lactiplantibacillus plantarum AR113. The results showed that L. plantarum Δ bsh 1 and Δ bsh 3 treatments did not improve body weight and alleviate the hyperactivated myeloperoxidase activity to the DSS group. However, the findings for L. plantarum AR113, L. plantarum Δ bsh 2 and Δ bsh 4 treatments were completely opposite. The double and triple bsh knockout strains further confirmed that BSH 1 and BSH 3 are critical for the ameliorative effects of L. plantarum AR113. In addition, L. plantarum Δ bsh 1 and Δ bsh 3 did not significantly inhibit the increase in pro-inflammatory cytokines or the decrease in an anti-inflammatory cytokine. These results suggest that BSH 1 and BSH 3 in L. plantarum play important roles in alleviating enteritis symptoms., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: This study aimed to evaluate the cut-off value of anti-Müllerian hormone (AMH) combined with body mass index (BMI) in the diagnosis of polycystic ovary syndrome (PCOS) and polycystic ovary morphology (PCOM)., Methods: This retrospective study included 15,970 patients: 3775 women with PCOS, 2879 women with PCOM, and 9316 patients as controls. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for AMH. We randomly divided the patients into two data sets. In dataset 1, a receiver operating characteristic (ROC) curve was generated to analyze the accuracy of basic AMH levels in diagnosing PCOS and PCOM. The optimal cut-off value was calculated in dataset 1 and validated in dataset 2, expressed as sensitivity and specificity., Results: In the PCOS group, obese patients had the lowest AMH levels, while underweight patients had the highest AMH level (P < 0.001). After adjusting for age, the ratio of luteinizing hormone (LH) and follicle stimulating hormone (FSH), serum testosterone level, and BMI, AMH was an independent predictor of PCOS and PCOM. In the group with BMI < 18.5 kg/m 2 , the optimistic AMH cut-off value was 5.145 ng/mL with a sensitivity of 84.3% and specificity of 89.1%, whereas in the BMI ≥ 28 kg/m 2 group, the optimistic AMH cut-off value was 3.165 ng/mL with a sensitivity of 88.7% and specificity of 74.6%. For the BMI range categories of 18.5-24, 24.0-28 kg/m 2 , the optimistic AMH cut-off values were 4.345 ng/mL and 4.115 ng/mL, respectively. The tendency that the group with lower weight corresponded to higher AMH cut-off values was also applicable to PCOM. In the same BMI category, patients with PCOM had a lower AMH diagnosis threshold than those with PCOS (< 18.5 kg/m 2 , 5.145 vs. 4.3 ng/mL; 18.5-24 kg/m 2 , 4.345 vs. 3.635 ng/mL; 24.0-28 kg/m 2 , 4.115 vs. 3.73 ng/mL; ≥ 28 kg /m 2 , 3.165 vs. 3.155 ng/mL). These cut-off values had a good diagnostic efficacy in the validation dataset. Based on different phenotypes and severity of ovulation disorders, the distribution of AMH in PCOS were also significantly different (P < 0.001)., Conclusions: AMH is a potential diagnostic indicator of PCOS and is adversely associated with BMI. The AMH cut-off value for diagnosing PCOS was significantly higher than that for PCOM., (© 2023. The Author(s).)

Aim: To identify DNA methylation markers for triage in a cohort of human papillomavirus-positive (HPV + ) women. Methods: The methylation markers were identified and evaluated for the detection of cervical high-grade squamous intraepithelial lesions (HSILs) or cervical cancer (collectively referred to as 'HSIL+') in HPV + women (n = 692). Results: Combined PAX1 / ST6GALNAC5 methylation testing yielded HSIL+ sensitivity of 0.838 and 0.818, with a specificity of 0.827 and 0.810, in the training and test sets, respectively. For cervical cancer, the specificity and sensitivity were 0.969 and 1.000 in the training set and 0.967 and 0.875 in the test set. Moreover, the combined marker methylation test (0.86; 77/90) was more sensitive than the cytology (0.31; 28/90) for HSIL+. Conclusion: The combined PAX1 / ST6GALNAC5 marker may have clinical application for detecting HSIL+ in HPV + women undergoing screening.

Historically, both p- and n-type PbTe show extraordinary thermoelectric figures of merit within 300-600 °C for power generation applications. A full realization of the potential of these high-performance thermoelectric materials on a device level largely depends on the electrical and thermal contacts with the metal electrodes. Chemical inertness with a slow diffusion could be an important criterion for the selection of metal electrodes. In this work, the diffusion of the total 12 potential metal electrodes in PbTe diffusion couples are focused on and sorted, suggesting the superiority of Co as an electrode for its low diffusion coefficient and interfacial contact resistivity, inertial to PbTe and compatibility in temperature for sintering. The strategy used in this work is believed to be applicable to the selection of electrodes for other thermoelectric materials.

Background: Few studies have evaluated the significance of sarcopenia in predicting the outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG), especially those who received neoadjuvant chemoradiotherapy (NCRT). We aimed to identify the sarcopenic status and its impact on the outcomes of patients with locally advanced AEG who received NCRT followed by radical surgery or systemic therapy., Materials and Methods: Patients with T3-4N+M0 AEG with accessible abdominal computed tomography (CT) before and after NCRT were retrospectively analyzed. Body composition parameters, particularly the skeletal muscle index (SMI), were assessed using a CT-based method, and sarcopenia was defined using a predetermined SMI cutoff value. Survival analysis was conducted using the Kaplan-Meier method. A Cox proportional hazards regression model was used to identify independent prognostic factors. Receiver operating characteristic curve analysis was carried out, and the area under the curve (AUC) was calculated to test the prognostic accuracy of different factors., Results: A total of 63 patients were enrolled, 65.1 and 79.4% of whom developed pre- and post-NCRT sarcopenia, respectively. Patients with pre-NCRT sarcopenia had lower radical surgery rates (70.7 vs . 95.5%, p = 0.047) than those without sarcopenia; however, sarcopenic status did not affect other short-term outcomes, including treatment-related toxicity and efficacy. Pre-NCRT sarcopenia was identified as an independent predictive factor for poor overall survival (OS) [adjusted hazard ratio (HR), 6.053; p = 0.002] and progression-free survival (PFS) (adjusted HR, 2.873; p = 0.031). Compared with nutritional indices such as the Nutritional Risk Screening 2002, weight loss during NCRT, and post-NCRT sarcopenia, pre-NCRT sarcopenia was regarded as the best predictive index for the 5-year OS (AUC = 0.735) and PFS rates (AUC = 0.770)., Conclusion: Pre-NCRT sarcopenia may be an independent predictive factor for OS and PFS rates in patients with locally advanced AEG receiving multimodal treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ming, Du, Geng, Li, Liu, Cai, Zhu, Zhang, Wang, Wang, Tang, Zhang, Peng, Wu, Bu, Peng, Yan, Li, Li, Li and Wang.)

The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC 50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment., Competing Interests: The authors declare the following competing financial interest(s): N.H., L.Z., W.Z., Q.T., H.Y., J.H., and Q.H. are co-inventors of patents that cover 3CLpro inhibitors in this study., (© 2023 The Authors. Published by American Chemical Society.)

Background: The role of preoperative serum tumor markers in HAS patients was vague, we designed the study to explore the effect of preoperative serum tumor markers on predicting the prognosis of HAS patients., Methods: A total of 139 patients were included according to the different tumor makers. X-tile tool was employed to identify the optimal cut-off values of respective tumor makers. Multivariate analyses were conducted to determine independent risk factors., Results: The optimal cut-off value of alpha-fetoprotein (AFP) for 3-years overall survival (OS) and recurrence-free survival (RFS) was 516 ng/mL. Patients with high-level AFP values assumed significantly worse OS and RFS than those with low-level AFP values (P = 0.028 and P = 0.011, respectively). The optimal cut-off value of Carbohydrate antigen (CA)19-9 for OS and RFS was 51.3 U/mL. And the survival results were similar with AFP in the aspects of OS and RFS (P = 0.009 and P < 0.001, respectively). Multivariate analyses showed that high serum AFP was an independent risk factor for OS and RFS of HAS patients (HR7.264; 95% CI 1.328-39.738; P = 0.022 and HR 2.688; 95% CI 0.922-7.836; P = 0.070, respectively). CA19-9 could perform as a fair substitute to predict the HAS patients' OS and RFS when the preoperative serum AFP was unavailable (HR 7.816; 95% CI 2.084-29.308; P = 0.002 and HR 4.386; 95% CI 1.824-10.547; P = 0.001, respectively). Other tumor markers didn't present significant influences., Conclusions: Applying preoperative serum AFP level to predict the HAS patients' prognosis is feasible and preoperative serum high-AFP is an independent risk factor for OS and RFS of HAS patients. Preoperative serum CA19-9 could be an alternative choice when AFP was absent., (© 2023. The Author(s).)

Bayesian neural network (BNN) allows for uncertainty quantification in prediction, offering an advantage over regular neural networks that has not been explored in the differential privacy (DP) framework. We fill this important gap by leveraging recent development in Bayesian deep learning and privacy accounting to offer a more precise analysis of the trade-off between privacy and accuracy in BNN. We propose three DP-BNNs that characterize the weight uncertainty for the same network architecture in distinct ways, namely DP-SGLD (via the noisy gradient method), DP-BBP (via changing the parameters of interest) and DP-MC Dropout (via the model architecture). Interestingly, we show a new equivalence between DP-SGD and DP-SGLD, implying that some non-Bayesian DP training naturally allows for uncertainty quantification. However, the hyperparameters such as learning rate and batch size, can have different or even opposite effects in DP-SGD and DP-SGLD. Extensive experiments are conducted to compare DP-BNNs, in terms of privacy guarantee, prediction accuracy, uncertainty quantification, calibration, computation speed, and generalizability to network architecture. As a result, we observe a new tradeoff between the privacy and the reliability. When compared to non-DP and non-Bayesian approaches, DP-SGLD is remarkably accurate under strong privacy guarantee, demonstrating the great potential of DP-BNN in real-world tasks.

Background: Determining a non-invasive, serum-based diagnostic panel for early diagnosis of AD will play a significant role in the prevention and treatment of the disease., Methods: We performed standardized clinical assessments and neuroimaging measurements in 45 patients with AD and an equal number of sex - and age-matched controls. 48 target peptides of 14 identified target proteins were quantitatively analyzed by PRM., Results: 8 protein markers were screened, including SAA4, PPBP, PF4, APOA4, F10, CPB2, C1S and IGHM. An diagnosis panel including 8 proteins and demographic characteristics markers respectively was found to be the robust with a AUC of 92.3%., Conclusions: Our study developed a new panel including protein and demographic characteristics that could be used to distinguish AD from control candidates., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Purpose: The aim of the current study was to identify the relationship between body composition changes during neoadjuvant therapy (NAT) and the treatment efficiency of NAT in gastrointestinal cancer (GC) patients., Methods: From January 2015 to July 2020, 277 GC patients treated with NAT had included for retrospective analysis. The body mass index (BMI) and computed tomography (CT) imaging before and after NAT were recorded. The BMI change optimal cut-off value were calculated by ROC curve. Balancing essential characteristic variables using propensity score matching (PSM) method. Exploring the association between BMI changes and tumor response to NAT using logistic regression analysis. The survival outcome of matched patients between different BMI change groups was compared., Results: A cutoff point of BMI change >2% during NAT was defined as BMI loss. Among the 277 patients, 110 (39.7%) patients showed BMI change with a loss after NAT. In total, 71 pairs of patients were selected for further analysis. The median follow-up time was 22 months (range 3 to 63 months). Univariate and multivariate logistic regression analyses in matched cohort showed that BMI change was a prognostic factor for tumor response after NAT in GC patients (odds ratio (OR), .471; 95% confidence interval (CI), .233-.953; P = .036). In addition, patients who experienced BMI loss after NAT showed worse overall survival than those who had BMI gain or stable., Conclusion: BMI loss during NAT probably may has negative effects on NAT efficiency and survival for gastrointestinal cancer patients. It is necessary to monitor and maintain weight for patients during treatment.

Background: The tumor microenvironment (TME) has been shown to strongly influence treatment outcome for cancer patients in various indications and to influence the overall survival. However, the cells forming the TME in gastric cancer have not been extensively characterized., Results: We combine bulk and single-cell RNA sequencing from tumors and matched normal tissue of 24 treatment-naïve GC patients to better understand which cell types and transcriptional programs are associated with malignant transformation of the stomach. Clustering 96,623 cells of non-epithelial origin reveals 81 well-defined TME cell types. We find that activated fibroblasts and endothelial cells are most prominently overrepresented in tumors. Intercellular network reconstruction and survival analysis of an independent cohort imply the importance of these cell types together with immunosuppressive myeloid cell subsets and regulatory T cells in establishing an immunosuppressive microenvironment that correlates with worsened prognosis and lack of response in anti-PD1-treated patients. In contrast, we find a subset of IFNγ activated T cells and HLA-II expressing macrophages that are linked to treatment response and increased overall survival., Conclusions: Our gastric cancer single-cell TME compendium together with the matched bulk transcriptome data provides a unique resource for the identification of new potential biomarkers for patient stratification. This study helps further to elucidate the mechanism of gastric cancer and provides insights for therapy., (© 2022. The Author(s).)