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Abstract Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains are conjugated to nanoparticles, for the targeted delivery of rifampicin, imipenem, and ampicillin against bacterial pathogens. They show excellent specificity against their targets, and accumulate at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppress pathogen infections more effectively than 16 to 32-fold higher doses of free antibiotics. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.

This paper investigated the changes in microstructure, intermetallic compounds (IMC), and mechanical properties of Sn58Bi/Cu and Sn58Bi-0.6 Si3N4/Cu solder joints in the thermal aging process at 125 °C. With the increase of the thermal aging time, the Bi-phase was gradually coarsened, but the coarsening of the Bi-phase was suppressed after adding Si3N4 NPs. The thickness of the IMC increased continuously, and some areas even detached into the solder matrix, accompanied by gradual grain growth. For the samples with Si3N4 NPs, the IMC thickness significantly decreased, and the grain size was finer. Fractures mainly occur in the Bi-rich phase of the solder matrix following a brief period of thermal aging. However, as the aging time increases, the fracture location gradually shifts from the solder matrix to the IMC, resulting in intergranular and transgranular fractures. However, the shear strength of solder joints with added Si3N4 NPs was higher during the same aging period.

Abstract Reprogramming tumor‐associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF‐κB p65, MAPK p38 and JNK by glycolysis‐mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti‐PD‐L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

One of the current mainstream treatments for multiple myeloma (MM) is chemotherapy. However, due to the high clonal heterogeneity and genomic complexity of MM, single-target drugs have limited efficacy and are prone to drug resistance. Therefore, there is an urgent need to develop multi-target drugs against MM. We screened drugs that simultaneously inhibit poly(ADP-ribose) polymerase 1 (PARP1) and 20S proteasome through computer-aided drug discovery (CADD) techniques, and explored the binding mode and dynamic stability of selected inhibitor to proteasome through Molecular biology (MD) simulation method. Thus, the dual-target inhibition effect of fluzoparib was proposed for the first time, and the ability of dual-target inhibition and tumor killing was explored at the enzyme, cell and animal level, respectively. This provides a theoretical and experimental basis for exploring multi-target inhibitory drugs for cancers.

Abstract Background Despite the existence of available therapeutic interventions for HIV-1, this virus remains a significant global threat, leading to substantial morbidity and mortality. Within HIV-1-infected cells, the accessory viral protein r (Vpr) exerts control over diverse biological processes, including cell cycle progression, DNA repair, and apoptosis. The regulation of gene expression through DNA methylation plays a crucial role in physiological processes, exerting its influence without altering the underlying DNA sequence. However, a thorough examination of the impact of Vpr on DNA methylation in human CD4 + T cells has not been conducted. Methods In this study, we employed base-resolution whole-genome bisulfite sequencing (WGBS), real-time quantitative RCR and western blot to explore the effect of Vpr on DNA methylation of host cells under HIV-1 infection. Results We observed that HIV-1 infection leads to elevated levels of global DNA methylation in primary CD4 + T cells. Specifically, Vpr induces significant modifications in DNA methylation patterns, particularly affecting regions within promoters and gene bodies. These alterations notably influence genes related to immune-related pathways and olfactory receptor activity. Moreover, Vpr demonstrates a distinct ability to diminish the levels of methylation in histone genes. Conclusions These findings emphasize the significant involvement of Vpr in regulating transcription through the modulation of DNA methylation patterns. Together, the results of this investigation will considerably enhance our understanding of the influence of HIV-1 Vpr on the DNA methylation of host cells, offer potential avenues for the development of more effective treatments.

With the development of tunnel construction, the detection, control, and treatment of all kinds of tunnel lining diseases have received increased attention. Therefore, tunnel nondestructive testing technology is widely used as an intelligent emerging technology. Due to the cost limitations of industrial applications, nondestructive testing technology of medium- and small-shield tunnels experiences serious losses in accuracy and speed when transferred to large-diameter shield tunnels. A large shield tunnel forming quality inspection vehicle is developed by integrating a two-dimensional (2D) laser scanner with a wheel shaft encoder and an industrial computer. Based on this equipment, an asymmetric shield quality inspection method based on digital images is proposed. By analyzing the construction environment of a large-diameter shield tunnel, the ground and vehicle body point clouds are filtered, the central axis is extracted using the neighborhood vector method, and the central coordinate system of the tunnel is established. The inspection route is arranged eccentrically, and the sampling point clouds are divided into dense and sparse side point clouds according to their tunnel density. Moreover, different methods are used to pick up the joint features of the segment. The dense side point cloud is expanded around the central axis into a 2D gray image, and the joint image is segmented by scaling, normalization, and gradient threshold segmentation. According to the classification of joints based on the linear equation, the linear distribution formula of sparse and dense side joints is deduced by combining the segment structure and the point placement, with the sparse side joints picked up indirectly. According to the joint characteristic points, the edge point clusters on both sides of the segment and the segment misalignment are calculated. The least square method is used to fit the tunnel point cloud and calculate tunnel ellipticity. Tests are conducted in a large-diameter shield tunnel to verify the effectiveness of the inspection method, and the following conclusions are made from the test results: The inspection speed of the molding quality inspection vehicle in the 14-meter shield tunnel is 3 km·h−1; compared with traditional detection methods, the average deviation of segment dislocation detection is less than 2 mm; the average deviation of tunnel contour maximum deformation detection is less than 2 mm, and the average deviation of ovality detection is less than 0.1%. This meets the high-speed, high-precision, and low-cost requirements of large-diameter shield tunnel molding quality inspections.

ABSTRACT: Environmental pollution poses a significant challenge to the poultry industry, leading to substantial losses and adverse effects on the health, production, and performance of avian species. In recent years, there has been growing interest in exploring natural compounds with potential protective effects against cadmium (Cd)-induced toxicity. Luteolin (LUT), a flavonoid found in various plants, has been studied for its antioxidant, anti-inflammatory, and cytoprotective properties. In this study, Su green shell grass chickens were divided into 4 groups: control, LUT (150 mg LUT), Cd (100 mg CdCl2), and Cd + LUT (100 mg CdCl2 + 150 mg LUT) groups for 1 month, respectively. The present study revealed that LUT maintained the morphology and functional activity of the liver and intestine. LUT alleviated Cd-induced impairment in the liver and intestinal biochemical indicators, suppressed Cd-induced liver fibrosis, mitigated liver and intestinal tissue damage. Additionally, LUT reduced oxidative stress and regulated the Cd-induced impairment in trace elements of the liver and intestine. Furthermore, LUT reduced Cd-induced liver inflammation, restored Cd-induced intestinal barrier function, and normalized Cd-induced serum proteins, including changes in the content of glutamyltranspeptidase. Moreover, LUT maintained Cd-induced disruption of gut microbiota and alleviated bacterial dysbiosis. Overall, these findings suggest that LUT holds promise as a potential therapeutic agent for mitigating the adverse effects of Cd-induced toxicity in poultry, by preserving liver and intestinal health, reducing oxidative stress, inflammation, and restoring gut microbiota balance.

Adhesions are the most common complication of abdominal or pelvic surgery and remain a challenging problem. To better understand the development tendency of abdominal adhesions, we performed a comprehensive bibliometric analysis of the field of abdominal adhesions. In total, 2219 articles regarding abdominal adhesions were screened and analyzed from 3410 manuscripts indexed in the Web of Science-indexed manuscripts regarding abdominal adhesion from 2004 to 2023. A bibliometric analysis was performed, and CiteSpace [version 6.2. R3 (64-bit)] and VOSviewer (version 1.6.19) were used to visualize the results. The number of annual publications showed slight growth before 2019, and the USA contributed the most publications. The most prolific author in this domain was Diamond, while the publications from Ten Broek had the strongest influence. The most popular journal in this field was the Journal of Surgical Research, and the most frequently co-cited journal was Fertility and Sterility. After analyzing the keywords, “prevention”, “surgery” and “peritoneal adhesion” were the 3 most co-cited keywords, while “adhesive small bowel obstruction” was the strongest keyword in the citation burst. Here, for the first time, we used bibliometric methods to study abdominal adhesions over the past ten years. By summarizing the characteristics of publications and predicting future research prospects, we established a framework for researchers and provided a basis for subsequent research.

The global ecosystem dynamics investigation (GEDI) mission aims to provide large-scale, high-precision, and high-frequency measurements of the Earth's three-dimensional structures. However, uncertain geolocation error may hinder or restrict the further application of GEDI products. Based on the error matrix, the laser spot center positioning method was employed to quickly evaluate and quantify the geolocation errors of GEDI L2A (version 2) data in the high-latitude region of China, thereby reducing the impact of systematic geolocation errors on elevation and canopy height detection performance. Combining with high-resolution airborne light detection and ranging data, we provided the geolocation offset characteristics at footprint, beam, and orbit scales, while monitoring their performance over nearly a year. Correcting geolocation errors at the footprint scale can significantly enhance the elevation accuracy, butit has the largest standard deviation (approximately 15 m). Conversely, at the orbit and beam scales, the standard deviations of along- and cross-track error are smaller and the ability to improve elevation accuracy is lower. At beam scale, the level of improvement in elevation accuracy increases with the slope but diminishes when the slope exceeds 20°. Unfortunately, the effect of geolocation correction on canopy height accuracy in this study area is not obvious. Over time, GEDI's elevation detection performance exhibits greater stability, whereas canopy height accuracy decreases as the leaf on season transitions to the leaf off season. The proposed approach provides a rapid solution for preliminary evaluation (beam and orbit scale) and detailed assessment (footprint scale) of GEDI's geolocation errors, thereby laying the groundwork for its future applications.

Abstract The World Health Organization (WHO) prioritizes pneumococcal disease as a vaccine-preventable disease and recommends the inclusion of pneumococcal conjugate vaccines (PCV) in national immunization programs worldwide. However, PCV is not included in the National Immunization Program in China and has low vaccination coverage due to its high cost. To address this, Weifang City implemented an innovative strategy for a 13-valent PCV (PCV13) on June 1, 2021. This strategy aimed to provide one dose of PCV13 free of charge for children aged 6 months to 2 years in registered households and to adopt a commercial insurance model with one dose of PCV13 free of charge in 2023 for children over 2 years old. The Health Commission of Weifang and other departments conducted a comprehensive investigation and considered various factors, such as vaccine effectiveness, safety, accessibility, vaccine price, and immunization schedules, for eligible children (under 5 years old). Stakeholder opinions were also solicited before implementing the policy. The Commission negotiated with various vaccine manufacturers to maximize its negotiating power and reduce vaccine prices. The implementation plan was introduced under the Healthy Weifang Strategy. Following the implementation of this strategy, the full course of vaccination coverage increased significantly from 0.67 to 6.59%. However, vaccination coverage is still lower than that in developed countries. Weifang's PCV13 vaccination innovative strategy is the first of its kind in Chinese mainland and is an active pilot of non-immunization program vaccination strategies. To further promote PCV13 vaccination, Weifang City should continue to implement this strategy and explore appropriate financing channels. Regions with higher levels of economic development can innovate the implementation of vaccine programs, broaden financing channels, improve accessibility to vaccination services, and advocate for more localities to incorporate PCV13 into locally expanded immunization programs or people-benefiting projects. A monitoring and evaluation system should also be established to evaluate implementation effects. Graphical Abstract

The assessment of disaster-causing hazards for the rainstorm event is a fundamental and key aspect of assessing the risk of rainstorm disasters, which can provide essential technical support for meteorological disaster prevention and mitigation. Using the hourly and daily precipitation data from 7 national meteorological observation stations and 120 regional automatic weather stations in Xiaogan City, as well as geographic information data, etc., a regional rainstorm event disaster-causing hazard that occurred in Xiaogan City on 12 August 2021 was evaluated base on dynamic assessment method of disaster hazard assessment of rainstorm process. By analyzing rainfall characteristic quantity, the disaster-causing factors were identified. Four disaster-causing factors were calculated using the information entropy-weight method, and the rainstorm event intensity index was calculated. The topographic-effected indices and the drainage-effected indices were determined as environmental factors based on analyzing the underlying surface characteristics in the rainstorm area. Then a synthetical index of disaster-prone environment was calculated using equal weighted summation of these indices. The disaster-causing hazard indices of the rainstorm event are composed of the weighted intensity indices of rainfall and the synthetical indices of disaster-prone environment. It was divided into five levels by using the Jenks natural breaks method, and the hazard level zonation chart for the rainstorm event was created using GIS. Finally, the hazard evaluation results were validated by the real rainstorm disaster data from the main affected area. The main results are as follows. (1) The "8.12" rainstorm event was characterized by its suddenness, heavy short-term rainfall, and concentrated precipitation, with 86.1% precipitation concentrated in 6 hours, and maximum precipitation in 6 hours of being up to a 50-year recurrence period, so the disaster-causing factors were selected by mainly considering the short-term precipitation. (2) The highest-level disaster hazard zones are located in most of Xiaonan district, central Yunmeng, north-east Yingcheng City, and southwest Anlu City, while the higher-level disaster hazard zone covers almost all the central part of Xiaogan City. Note that the results depend on the rainstorm intensity, the environment of the terrain, and the river network. (3) The highest- and higher-level hazard zones were areas corresponding to the regions with heavy rainstorm damage, with the actual disaster level reaching the "major" disaster level. The hazard assessment results actually reflected the actual losses in the main affected area.

Abstract Background Whether body mass index (BMI) is a risk factor for poor bowel preparation is controversial, and the optimal bowel preparation regimen for people with a high BMI is unclear. Methods We prospectively included 710 individuals with high BMIs (≥ 24 kg/m2) who were scheduled to undergo colonoscopy from January to November 2021 at 7 hospitals. Participants were randomly allocated into 3 L split-dose polyethylene glycol (PEG) group (n=353) and 2 L PEG group (n=357). The primary outcome was the rate of adequate bowel preparation, and the secondary outcomes included Boston Bowel Preparation Scale (BBPS) score, polyp detection rate, cecal intubation rate, and adverse reactions during bowel preparation. Furthermore, we did exploratory subgroup analyses for adequate bowel preparation. Results After enrollment, 15 individuals didn’t undergo colonoscopy, finally 345 participants took 3 L split-dose PEG regimen, and 350 participants took 2 L PEG regimen for colonoscopic bowel preparation. 3 L split-dose PEG regimen was superior to 2 L PEG regimen in the rate of adequate bowel preparation (81.2% vs. 74.9%, P = 0.045), BBPS score (6.71±1.15 vs. 6.37±1.31, P < 0.001), and the rate of polyp detection (62.0% vs. 52.9%, P = 0.015). The cecal intubation rate was similar in both groups (99.7%). Regarding adverse reactions, individuals were more likely to feel nausea in the 3 L PEG group (30.9% vs. 19.3%; P = 0.001); however, the degree was mild. In the subgroup analysis for adequate bowel preparation, 3 L split-dose PEG regimen performed better than 2 L PEG regimen in the overweight (BMI 25-29.9 kg/m2 ) (P = 0.006) and individuals with constipation (P = 0.044), while no significant differences were observed in relatively normal (BMI 24-24.9 kg/m2) (P = 0.593) and obese individuals (BMI ≥ 30 kg/m2) (P = 0.715). Conclusions 3 L split-dose PEG regimen is superior to 2 L PEG regimen for colonoscopic Bowel Preparation in relatively high-BMI individuals, especially overweight individuals (BMI 25-29.9 kg/m2 ). Trial Registration This trial was registered in the Chinese Clinical Trials Registry (ChiCTR2000039068). The date of first registration, 15/10/2020, http://www.chictr.org.cn

Polypropylene (PP) has garnered significant attention as a cable insulation material due to its exceptional electrical performance and recyclability. Styrene-grafted polypropylene (PP-g) emerges as a promising alternative in this context. This study employs thermogravimetric-gas chromatography experiments and reactive molecular dynamics simulations to compare the pyrolysis process and decomposition products of pure PP and PP-g as cable insulation materials. Results indicate that while both materials produce similar pyrolysis products, PP-g exhibits greater resistance to decomposition than PP. The predominant hydrocarbons in the decomposition products include methane (CH4), ethylene (C2H4), propylene (C3H6), and ethane (C2H6). The relative proportion of hydrocarbons decreases with increasing temperature, with a shift toward increased C2H6 production. The ratio of C2H6 to (CH4 + C2H4) molecular weights in thermal decomposition products rises with temperature, suggesting enhanced stability. Graft modification alters the decomposition pathway, specifically increasing the generation of C2H6. This study lays a theoretical foundation for cable aging monitoring and life assessment.

Abstract Exploring the role of phase separation in intracellular compartment formation is an active area of research. However, the associations of phase separation with intestinal stem cell (ISC)-dependent regeneration and aging remain unclear. Here, we demonstrate that BuGZ, a coacervating mitotic effector, shows age- and injury-associated condensation in Drosophila ISC nuclei during interphase. BuGZ condensation promotes ISC proliferation, affecting Drosophila gut repair and longevity. Moreover, m6A reader YT521-B acts as the transcriptional and functional downstream of BuGZ. The binding of YT521-B promotor or m6A writer Ime4/ Mettl14 to BuGZ controls its coacervation, indicating that the promotor may accelerate the phase transition of its binding transcription factor. Hence, we propose that phase separation and m6A regulators may be critical for ameliorating ISC-dependent gut regeneration and aging and requires further study.

Abstract Background Intestinal ischemia-reperfusion injury occurs in acute intestinal obstruction, intussusception, acute mesenteric artery embolism, and other diseases and can lead to local intestinal necrosis, distant organ involvement, or systemic reactions, with high morbidity and mortality. Ferroptosis plays a crucial role in intestinal ischemia-reperfusion injury, and inhibition of ferroptosis may provide new approaches for treating the disease. SIRT3 protects cells from oxidative stress and may be involved in the process of ferroptosis. We hypothesized that resveratrol, an agonist of SIRT3, could ameliorate intestinal ischemia-reperfusion injury by compensating the GSH/GPX4 pathway. Methods Intestinal ischemia-reperfusion (I/R) and Caco-2 hypoxia-reoxygenation models were established. Transmission electron microscopy was used to assess mitochondrial function; the Chiu’s score was used to evaluate the degree of intestinal mucosal injury based on HE staining; and Western blot was used to detect the SIRT3/FoxO3a pathway, tight junction proteins and ferroptosis-related protein expression. Sirt3 -/- C57, shSIRT3-Caco-2 cells and siFoxO3a-Caco-2 cells were established. C11-BODIPY was used to detect lipid peroxide in cells; FD4 and IFABP were used to detect intestinal permeability; MitoSOX was used to detect ROS levels; and MitoTracker and immunofluorescence colocalization were used to detect SIRT3 levels. Results In the intestinal I/R model, I/R injury occurs mainly during the reperfusion period and leads to ferroptosis through the GSH/GPX4 pathway. Resveratrol could reduce ferroptosis and ameliorate I/R injury by activating SIRT3. In Sirt3-/- mice, more intestinal mucosal cells underwent ferroptosis, I/R injury was more severe, and resveratrol lost the ability to ameliorate I/R injury. In addition, hypoxia-reoxygenation increased RSL3-induced ferroptosis sensitivity in Caco-2 cells in vitro. In the presence of shSIRT3 or RSL3 alone, resveratrol could ameliorate Caco-2 ferroptosis, but not RSL3-induced shSIRT3-Caco-2 ferroptosis. Furthermore, resveratrol might activate the SIRT3/FoxO3a pathway, increase the expression of SOD2 and catalase, and inhibit ROS generation, thus reducing lipid peroxidation and ferroptosis. Conclusion To date, this is the first study to show that resveratrol ameliorates intestinal ischemia-reperfusion injury by activating SIRT3 and reducing ferroptosis. Resveratrol can reduce intestinal ischemia-reperfusion injury by activating the SIRT3/FoxO3a pathway, increasing the expression of SOD2 and catalase, reducing ROS and LPO production, compensating for the GSH/GPX4 pathway and inhibiting ferroptosis. Graphical abstract Resveratrol increases the expression of SOD2 and catalase, reduces the production of ROS and LPO, compensates for the GSH/GPX4 pathway and inhibits ferroptosis by activating the SIRT3/FoxO3a pathway

Abstract Organic electrocatalytic conversion is an essential pathway for the green conversion of low-cost organic compounds to high-value chemicals, which urgently demands the development of efficient electrocatalysts. Here, we report a Cu single-atom dispersed Rh metallene arrays on Cu foam for cathodic nitrobenzene electroreduction reaction and anodic methanol oxidation reaction. In the coupled electrocatalytic system, the Cusingle-atom-Rh metallene arrays on Cu foam requires only the low voltages of 1.18 V to reach current densities of 100 mA cm−2 for generating aniline and formate, with up to ~100% of nitrobenzene conversion/ aniline selectivity and over ~90% of formate Faraday efficiency, achieving synthesis of high-value chemicals. Density functional theory calculations reveal the electron effect between Cu single-atom and Rh host and catalytic reaction mechanism. The synergistic catalytic effect and H*-spillover effect can improve catalytic reaction process and reduce energy barrier for reaction process, thus enhancing electrocatalytic reaction activity and target product selectivity.

Abstract Lipid metabolic reprogramming is an emerging hallmark of cancer. In order to sustain uncontrolled proliferation and survive in unfavorable environments that lack oxygen and nutrients, tumor cells undergo metabolic transformations to exploit various ways of acquiring lipid and increasing lipid oxidation. In addition, stromal cells and immune cells in the tumor microenvironment also undergo lipid metabolic reprogramming, which further affects tumor functional phenotypes and immune responses. Given that lipid metabolism plays a critical role in supporting cancer progression and remodeling the tumor microenvironment, targeting the lipid metabolism pathway could provide a novel approach to cancer treatment. This review seeks to: (1) clarify the overall landscape and mechanisms of lipid metabolic reprogramming in cancer, (2) summarize the lipid metabolic landscapes within stromal cells and immune cells in the tumor microenvironment, and clarify their roles in tumor progression, and (3) summarize potential therapeutic targets for lipid metabolism, and highlight the potential for combining such approaches with other anti-tumor therapies to provide new therapeutic opportunities for cancer patients.

Background and aims: The primary goal of chronic hepatitis B (CHB) treatment is to reduce hepatitis B surface antigen (HBsAg). T helper 17 (Th17) and regulatory T (Treg) cells are essential for the development of CHB. However, how Th17 and Treg cells contribute to HBsAg loss is still unknown. Therefore, this study aimed to search for the predictive value of Th17 and Treg cells for HBsAg loss in CHB patients with low HBsAg quantification. Methods: The study included 99 hepatitis B e antigen (HBeAg)-negative CHB patients who had completed a year of nucleos(t)ide analogue (NA) monotherapy and had received both NA and pegylated interferon (PEG-IFN) treatment for less than 96 weeks (96 wk). In the cured group, 48 patients lost HBsAg within 48 wk, while 51 patients did not (uncured group). Blood samples and clinical data were collected for research. Results: During PEG-IFN and NA combination therapy, the proportion of Th17 cells in the cured group increased significantly, while the proportion of Treg cells in the uncured group increased. From 0 to 24 wk, the proportion of Th17 cells in the cured group was significantly higher than in the uncured group, while the opposite was true for Treg cells. Patients with alanine aminotransferase (ALT) ≥ 2.5 upper limit of normal (ULN) at 12 wk had a higher proportion of Th17 cells and a lower proportion of Treg cells than those with ALT

The extraction of urban road features provides indispensable support to numerous high-accurate applications such as autonomous driving and urban high-definition mapping. However, approaches mainly focus on road connectivity, while often overlooking finer details of urban road constituent structures. Data that captures road details, such as LiDAR, may not be always readily available. This article proposes an operational framework for mapping fine-grained urban road features by integrating open-source data (OSD). The geometric measurement method is successively presented using projective geometry and prior knowledge for urban road sections. And a feature generation strategy is introduced to achieve and express the fine-grained road features. Compared with the corresponding large-scale topographic map (LTM) and available optical remote sensing image (AORSI), the proposed method regenerated fine-grained features of urban roads with m-level. It provides a cost-effective innovative and alternative method to acquiring fine-grained road datasets in other data-scarce regions.

Epstein-Barr virus (EBV) is associated with several types of human cancer including nasopharyngeal carcinoma (NPC). The activation of EBV to the lytic cycle has been observed in advanced NPC and is believed to contribute to late-stage NPC development. However, how EBV lytic cycle promotes NPC progression remains elusive. Analysis of clinical NPC samples indicated that EBV reactivation and immunosuppression were found in advanced NPC samples, as well as abnormal angiogenesis and invasiveness. To investigate the role of the EBV lytic cycle in tumor development, we established a system that consists of two NPC cell lines, respectively, in EBV abortive lytic cycle and latency. In a comparative analysis using this system, we found that the NPC cell line in EBV abortive lytic cycle exhibited the superior chemotactic capacity to recruit monocytes and polarized their differentiation toward tumor-associated macrophage (TAM)-like phenotype and away from DCs, compared to EBV-negative or EBV-latency NPC cells. EBV-encoded transcription activator ZTA is responsible for regulating monocyte chemotaxis and TAM phenotype by up-regulating the expression of GM-CSF, IL-8, and GRO-α. As a result, TAM induced by EBV abortive lytic cycle promotes NPC angiogenesis, invasion, and migration. Overall, this study elucidated the role of the EBV lytic life cycle in the late development of NPC and revealed a mechanism underlying the ZTA-mediated establishment of the tumor microenvironment (TME) that promotes NPC late-stage progression.

The antibiotic resistance of Acinetobacter baumannii poses a significant threat to global public health, especially those strains that are resistant to carbapenems. Therefore, novel strategies are desperately needed for the treatment of infections caused by antibiotic-resistant A. baumannii. In this study, we report that brevicidine, a bacterial non-ribosomally produced cyclic lipopeptide, shows synergistic effects with multiple outer membrane-impermeable conventional antibiotics against A. baumannii. In particular, brevicidine, at a concentration of 1 μM, lowered the minimum inhibitory concentration of erythromycin, azithromycin, and rifampicin against A. baumannii strains by 32–128-fold. Furthermore, mechanistic studies were performed by employing erythromycin as an example of an outer membrane-impermeable conventional antibiotic, which showed the best synergistic effects with brevicidine against the tested A. baumannii strains in the present study. The results demonstrate that brevicidine disrupted the outer membrane of A. baumannii at a concentration range of 0.125–4 μM in a dose-dependent manner. This capacity of brevicidine could help the tested outer membrane-impermeable antibiotics enter A. baumannii cells and thereafter exert their antimicrobial activity. In addition, the results show that brevicidine–erythromycin combination exerted strong A. baumannii killing capacity by the enhanced inhibition of adenosine triphosphate biosynthesis and accumulation of reactive oxygen species, which are the main mechanisms causing the death of bacteria. Interestingly, brevicidine and erythromycin combination showed good therapeutic effects on A. baumannii-induced mouse peritonitis–sepsis models. These findings demonstrate that brevicidine is a promising sensitizer candidate of outer membrane-impermeable conventional antibiotics for treating A. baumannii infections in the post-antibiotic age.

Chickens are a major source of meat and eggs in human food and have significant economic value. Cadmium (Cd) is a common environmental pollutant that can contaminate feed and drinking water, leading to kidney injury in livestock and poultry, primarily by inducing the generation of free radicals. It is necessary to develop potential medicines to prevent and treat Cd-induced nephrotoxicity in poultry. Luteolin (Lut) is a natural flavonoid compound mainly extracted from peanut shells and has a variety of biological functions to defend against oxidative damage. In this study, we aimed to demonstrate whether Lut can alleviate kidney injury under Cd exposure and elucidate the underlying molecular mechanisms. Renal histopathology and cell morphology were observed. The indicators of renal function, oxidative stress, DNA damage and repair, NAD+ content, SIRT1 activity, and autophagy were analyzed. In vitro data showed that Cd exposure increased ROS levels and induced oxidative DNA damage and repair, as indicated by increased 8-OHdG content, increased γ-H2AX protein expression, and the over-activation of the DNA repair enzyme PARP-1. Cd exposure decreased NAD+ content and SIRT1 activity and increased LC3 II, ATG5, and particularly p62 protein expression. In addition, Cd-induced oxidative DNA damage resulted in PARP-1 over-activation, reduced SIRT1 activity, and autophagic flux blockade, as evidenced by reactive oxygen species scavenger NAC application. The inhibition of PARP-1 activation with the pharmacological inhibitor PJ34 restored NAD+ content and SIRT1 activity. The activation of SIRT1 with the pharmacological activator RSV reversed Cd-induced autophagic flux blockade and cell injury. In vivo data demonstrated that Cd treatment caused the microstructural disruption of renal tissues, reduced creatinine, and urea nitrogen clearance, raised MDA content, and decreased the activities or contents of antioxidants (GSH, T-SOD, CAT, and T-AOC). Cd treatment caused oxidative DNA damage and PARP-1 activation, decreased NAD+ content, decreased SIRT1 activity, and impaired autophagic flux. Notably, the dietary Lut supplement observably alleviated these alterations in chicken kidney tissues induced by Cd. In conclusion, the dietary Lut supplement alleviated Cd-induced chicken kidney injury through its potent antioxidant properties by relieving the oxidative DNA damage-activated PARP-1-mediated reduction in SIRT1 activity and repairing autophagic flux blockade.

Laccases from white-rot fungi catalyze lignin depolymerization, a critical first step to upgrading lignin to valuable biodiesel fuels and chemicals. In this study, a wildtype laccase from the basidiomycete Fomitiporia mediterranea (Fom_lac) and a variant engineered to have a carbohydrate-binding module (Fom_CBM) were studied for their ability to catalyze cleavage of β-O-4′ ether and C–C bonds in phenolic and non-phenolic lignin dimers using a nanostructure-initiator mass spectrometry-based assay. Fom_lac and Fom_CBM catalyze β-O-4′ ether and C–C bond breaking, with higher activity under acidic conditions (pH < 6). The potential of Fom_lac and Fom_CBM to enhance saccharification yields from untreated and ionic liquid pretreated pine was also investigated. Adding Fom_CBM to mixtures of cellulases and hemicellulases improved sugar yields by 140% on untreated pine and 32% on cholinium lysinate pretreated pine when compared to the inclusion of Fom_lac to the same mixtures. Adding either Fom_lac or Fom_CBM to mixtures of cellulases and hemicellulases effectively accelerates enzymatic hydrolysis, demonstrating its potential applications for lignocellulose valorization. We postulate that additional increases in sugar yields for the Fom_CBM enzyme mixtures were due to Fom_CBM being brought more proximal to lignin through binding to either cellulose or lignin itself.

This paper discusses optimizing desktop image quality and bandwidth consumption in remote IoT GUI desktop scenarios. Remote desktop tools, which are crucial for work efficiency, typically employ image compression techniques to manage bandwidth. Although JPEG is widely used for its efficiency in eliminating redundancy, it can introduce quality loss with increased compression. Recently, deep learning-based compression techniques have emerged, challenging traditional methods like JPEG. This study introduces an optimized RFB (Remote Frame Buffer) protocol based on a convolutional neural network (CNN) image compression algorithm, focusing on human visual perception in desktop image processing. The improved RFB protocol proposed in this paper, compared to the unoptimized RFB protocol, can save 30–80% of bandwidth consumption and enhances remote desktop image quality, as evidenced by improved PSNR and MS-SSIM values between the remote desktop image and the original image, thus providing superior desktop image transmission quality.

Gastrointestinal cancer remains a significant global health burden. The pursuit of advancing the comprehension of tumorigenesis, along with the identification of reliable biomarkers and the development of precise therapeutic strategies, represents imperative objectives in this field. Exosomes, small membranous vesicles released by most cells, commonly carry functional biomolecules, including noncoding RNAs (ncRNAs), which are specifically sorted and encapsulated by exosomes. Exosome-mediated communication involves the release of exosomes from tumor or stromal cells and the uptake by nearby or remote recipient cells. The bioactive cargoes contained within these exosomes exert profound effects on the recipient cells, resulting in significant modifications in the tumor microenvironment (TME) and distinct alterations in gastrointestinal tumor behaviors. Due to the feasibility of isolating exosomes from various bodily fluids, exosomal ncRNAs have shown great potential as liquid biopsy-based indicators for different gastrointestinal cancers, using blood, ascites, saliva, or bile samples. Moreover, exosomes are increasingly recognized as natural delivery vehicles for ncRNA-based therapeutic interventions. In this review, we elucidate the processes of ncRNA-enriched exosome biogenesis and uptake, examine the regulatory and functional roles of exosomal ncRNA-mediated intercellular crosstalk in gastrointestinal TME and tumor behaviors, and explore their potential clinical utility in diagnostics, prognostics, and therapeutics.

The epididymis is responsible for post-testicular sperm maturation as it provides a favorable environment for spermatozoa to gain the ability for movement and fertilization. The recent evidence has shown that, the spermatozoa are vulnerable to dynamic variations driven by various cellular exposure mechanisms mediated by epididymosomes. Exosomes provide new insight into a mechanism of intercellular communication because they provide direct evidence for the transfer of several important bio-active cargo elements (proteins, lipid, DNA, mRNA, microRNA, circular RNA, long noncoding RNA) between epididymis and spermatozoa. In broad sense, proteomic analysis of exosomes from epididymis indicates number of proteins that are involved in sperm motility, acrosomal reaction, prevent pre-mature sperm capacitation and male infertility. Pinpointing, how reproductive disorders are associated with bio-active cargo elements of nano-scale exosome in the male reproductive tract. Therefore, the current review presents evidence regarding the distinctive characteristics and functions of nano-scale exosome in the male reproductive tract in both pathological and physiological developments, and argue that these vesicles serve as an important regulator of male reproduction, fertility, and disease susceptibility.

Lane-level road maps are crucial for urban traffic management, autonomous driving, and vehicle navigations. Optical remote sensing image suffers from trees and buildings occlusion for lane-level road mapping due to the top-down view. While street view images (SVIs) have been used for road detection, however, most of the previous articles focused on extracting road in image space. The reconstruction of lane-level road maps with measurability in geographic space remains challenging. Hence, this article proposed an operational framework for extracting and reconstructing lane-level road maps from urban open access data. First, a sample strategy was used to collect SVIs based on OpenStreetMap (OSM) road central lines. Then, a deep-learning-based method was adopted to identify lanes accurately, and road width was extracted based on design knowledge and OSM information. Finally, the lane-level road map was reconstructed by integrating the lane and its width information. The proposed framework achieves the transformation from image space to geographic space. The case study shows that 82.43% of the roadway is accurately reconstructed in lane-level. The difference between the reconstructed width of the roadway and the reference true value is within the m-level and the RMSE is 0.32 m. The proposed method is cost-effective and accurate-acceptable for acquiring lane-level road datasets in cities.

In this work, a machine learning-based energy management system is developed using a long short-term memory (LSTM) network for fuel cell hybrid buses. The neural network implicitly learns the complex relationship between various factors and the optimal power control from massive data. The selection of the neural network inputs is inspired by the adaptive Pontryagin’s minimum principle (APMP) strategy. Since an estimated value of the global average fuel cell power is required in the machine learning-based energy management strategy (EMS), some global features of driving cycles are extracted and then applied in a feedforward neural network to predict the average fuel cell power appropriately. The effectiveness of the machine learning-based energy management, with the integration of the mechanism of estimating the average fuel cell power based on the forward neural network, is tested under two different driving cycles from the training environment, with comparisons to a commercially used rule-based strategy. Based on the simulation results, the learning-based strategy outperforms the rule-based strategy regarding the charge-sustaining mode conditions and fuel economy. Moreover, compared to the best offline hydrogen consumption, the machine learning-based strategy consumed 0.58% and 0.36% more than the best offline results for both driving cycles. In contrast, the rule-based strategy consumed 1.80% and 0.96% more than optimal offline results for the two driving cycles, respectively. Finally, simulations under battery and fuel cell aging conditions show that the fuel economy of the machine learning-based strategy experiences no performance degradation under components aging compared to offline strategies.

HIV-1 latency posts a major obstacle for HIV-1 eradication. Currently, no desirable latency reversing agents (LRAs) have been implicated in the “Shock and Kill” strategy to mobilize the latently infected cells to be susceptible for clearance by immune responses. Identification of key cellular pathways that modulate HIV-1 latency helps to develop efficient LRAs. In this study, we demonstrate that the Wnt downstream β-catenin/TCF1 pathway is a crucial modulator for HIV-1 latency. The pharmacological activation of the β-catenin/TCF1 pathway with glycogen synthase kinase-3 (GSK3) inhibitors promoted transcription of HIV-1 proviral DNA and reactivated latency in CD4+ T cells; the GSK3 kinase inhibitor 6-bromoindirubin-3′-oxime (6-BIO)-induced HIV-1 reactivation was subsequently confirmed in resting CD4+ T cells from cART-suppressed patients and SIV-infected rhesus macaques. These findings advance our understanding of the mechanisms responsible for viral latency, and provide the potent LRA that can be further used in conjunction of immunotherapies to eradicate viral reservoirs.

In order to efficiently enrich IgG, reduce waste of bovine colostrum and improve the product value, the combined microfiltration-ultrafiltration technology was used to enrich IgG in bovine colostrum whey. First, the application of microfiltration technology in the sterilization of bovine colostrum whey was studied, and its operation process was optimized. Second, bovine colostrum whey after microfiltration sterilization was enriched by ultrafiltration technology, on the basis of single factor experiment, the ultrafiltration process was optimized by response surface, and the quality of enriched bovine colostrum whey was analyzed. The results showed that the best process parameters of bovine colostrum whey microfiltration were: Microfiltration pressure was 0.2 MPa, temperature was 30 ℃, the best process parameters of ultrafiltration enrichment were: Ultrafiltration pressure was 0.15 MPa, temperature was 35 ℃, concentration multiple was 6 times and dilution times was 4 times. According to these conditions, microfiltration-ultrafiltration operation of bovine colostrum whey was carried out, IgG concentration rate was 58.19%, and the membrane flux was 204.46 L/m2·h. The quality analysis of enriched bovine colostrum whey showed: The IgG content was 22760 µg/mL, IgG activity was 718.31 IU/L, protein content was 7.86%, fat content was 0.035%, and the total number of colonies was 2.4 lg CFU/ mL. This study provides a reference for further development and comprehensive utilization of IgG in bovine colostrum whey.

Exploiting coalbed methane can optimize the energy mix and improve safety in coal mines. Coalbed methane production commonly requires that the coal’s permeability be enhanced. However, conventional permeability enhancement techniques commonly used at present have their own shortcomings, such as a limited range of permeability enhancement or high fracture initiation pressures Tree-type fracturing is one of the new techniques that are expected to eliminate the above-mentioned shortcomings and allow the efficient exploitation of coalbed methane reserves. The unclear of gas migration mechanism in tree-type fracturing limits the development of this technology. For this paper, a fluid–solid–gas coupling experimental system was assembled to study the changes in gas pressure and gas flow in gas-bearing coal after hydraulic fracturing. In the experiments, tree-type branch boreholes can effectively connect hydraulic fractures and surrounding natural cracks, increasing the scope and rate of gas extraction. The degree of connectivity of fractures (cracks and pores) will affect the gas desorption rate, which makes the gas flow trace “U” shaped lines. Tree-type hydraulic fracturing can increase the coal’s permeability by factors of 3.1 to 3.9, increase the effective drainage rate by factors of 1.23 to 1.41, and increase the proportion of gas drained by 3.7% to 5.5%. These results provide a reliable basis for additional research on tree-type fracturing and can aid in its engineering application.

Abstract. Acquired immune deficiency syndrome is still one of the most severe global infectious diseases that pose a significant threat to human health. With the successful application of antiretroviral therapy, productive replication of human immunodeficiency virus type 1 (HIV-1) can be effectively blocked; however, antiretroviral therapy alone cannot cure the infection because of the presence of a stable and reactivatable viral latent reservoir. Thus, it is of great importance to have a better comprehension of the mechanisms driving HIV-1 pathogenesis and long-term persistence in infected individuals, based on which to further discover novel targets for therapeutic applications to treat or even cure the infection. Various studies have revealed that cellular metabolism is a critical factor impacting the fate and intracellular activities of immune cells. Emerging evidence implies that the alternations of cellular metabolism induced by HIV-1 infection play an important role in HIV-1 pathogenesis. Consequently, a promising approach of “metabolism as a therapeutic target” raised the possibility of using metabolic reprogramming as a treatment option for chronic HIV-1 infection. In this review, we summarize the latest studies about the interplay of the hosts' reprogramming of glucose metabolism and HIV-1 infection and introduce potential applications of searching for hallmarks and therapeutic targets of metabolic interventions for HIV-1 infection.

Objective: To investigate the predictive value of material separation technology of spectral CT in Pfirrmann grading of lumbar intervertebral disc degeneration. Methods: Retrospective analysis was performed on 30 patients with lumbar disc herniation in our hospital from October 2020 to February 2021. Spectral CT scan and MRI scan were performed respectively. Grade 1-3 of Pfirrmann grading was classified into low grade group, while grade 4-5 was classified into high grade group. Water (calcium) concentration, water (HAP) concentration, calcium (water) concentration, HAP (water) concentration and Eff-Z of intervertebral disc were measured by spectral post-processing analysis software in the same ROI. Independent sample t est was used to compare the differences among parameters, furthermore, the ROC curve was drawn. The area under the curve was used to evaluate the diagnostic efficiency and select the optimal diagnostic threshold. Results: The concentrations of water (calcium) and water (HAP) in low-grade intervertebral discs were higher than those in high-grade intervertebral discs, while the concentrations of water (calcium), water (HAP) and Eff-Z in low-grade intervertebral discs, were lower than those in high-grade intervertebral discs, which held statistical significance. The ROC curve showed that water (calcium) concentration and water (HAP) concentration were less effective in diagnosing the difference between low-grade and high-grade discs. Calcium concentration holds certain diagnostic efficacy. HAP and Eff-Z hold high diagnostic efficacy. while Eff-Z shows better diagnostic efficacy with AUC of 0.97. Taking 7.69 as the standard, the sensitivity and specificity of differentiating low-grade and high-grade intervertebral discs are respectively 96.25% and 96.00%. Conclusion: Spectral CT with multi-parameters quantitative analysis holds certain value in distinguishing low grade and high grade intervertebral discs.

Abstract Background Plant cell walls are interwoven structures recalcitrant to degradation. Native and adapted microbiomes can be particularly effective at plant cell wall deconstruction. Although most understanding of biological cell wall deconstruction has been obtained from isolates, cultivated microbiomes that break down cell walls have emerged as new sources for biotechnologically relevant microbes and enzymes. These microbiomes provide a unique resource to identify key interacting functional microbial groups and to guide the design of specialized synthetic microbial communities. Results To establish a system assessing comparative microbiome performance, parallel microbiomes were cultivated on sorghum (Sorghum bicolor L. Moench) from compost inocula. Biomass loss and biochemical assays indicated that these microbiomes diverged in their ability to deconstruct biomass. Network reconstructions from gene expression dynamics identified key groups and potential interactions within the adapted sorghum-degrading communities, including Actinotalea, Filomicrobium, and Gemmatimonadetes populations. Functional analysis demonstrated that the microbiomes proceeded through successive stages that are linked to enzymes that deconstruct plant cell wall polymers. The combination of network and functional analysis highlighted the importance of cellulose-degrading Actinobacteria in differentiating the performance of these microbiomes. Conclusions The two-tier cultivation of compost-derived microbiomes on sorghum led to the establishment of microbiomes for which community structure and performance could be assessed. The work reinforces the observation that subtle differences in community composition and the genomic content of strains may lead to significant differences in community performance. Video Abstract

In 2002 and 2020–2022, KH-9 HEXAGON mapping camera system (MCS) and panoramic camera system (PCS) images were made available to the public, respectively. Although great efforts have been made by the scientific community to develop applications that utilize KH-9 HEXAGON images, little attention has been paid to de-noising and contrast enhancement of these images particularly over urban landscapes. This paper focuses on developing a de-noising and contrast enhancement pipeline for KH-9 HEXAGON MCS and PCS over urban regions. The proposed approach employs first a wavelet transform trained using a suite of ‘degree of over-smoothing’ metrics (DOSM) for image de-noising. These metrics are sensitive to structure, texture, edges and local homogeneity of image objects. Then the de-noised image is subjected to the multi-resolution Top-hat to optimize the contrast. This method incorporates a range of shapes and neighborhoods at multiple scales. The method was applied to a KH-9 HEXAGON MCS image (acquired in 1975) and PCS image (acquired in 1974) representing a complex urban landscape, to support comprehensive evaluation under a range of settings. Performance was assessed against three state-of-the-art benchmark approaches: residual learning (deep learning), blind deconvolution and spatial filtering. To evaluate the performance of the proposed pipeline against the benchmarks, we employed the saturation image edge difference standard-deviation, co-occurrence metrics and the semivariogram. Additionally, the potential applications of pre-processed results were demonstrated using change detection, identification reference points and stereo images. The proposed method not only improved the quality of the KH-9 image across the different urban landscape types, but also preserved the original spatial characteristics of the image in comparison with the benchmark methods. At a time when understanding the nature of our changing planet is paramount, the proposed pipeline should be of great benefit to investigators wishing to use KH program images to extend their historical or time-series analyses further back in time.

Summary: Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during natural hepatitis C virus (HCV) infection contribute to virus clearance and what is the mechanism underlying remain unclear. Here, we demonstrated that treatment of HCV-infected hepatoma Huh7.5 cells with the IgGs purified from 2 of 28 (7.1%) chronic hepatitis C (CHC) patients efficiently controlled the infection, for which genotype 1b HVR1 (1bHVR1)-binding antibody was critical. Moreover, we found that 1bHVR1 peptide was superior to 2aHVR1 in rabbit immunization to elicit antibodies neutralizing genotypes 1a, 2a, 3a, and 4a. The neutralization effect of 1bHVR1 IgG could be augmented by HH-1, an antibody constructed from CHC memory B cells but without binding to HVR1 peptide. Mechanistic studies showed that 1bHVR1 antisera and IgGs disrupted the interaction of E2-SR-B1 receptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established infections of multiple HCV genotypes.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of novel coronavirus disease (COVID-19). The neutralizing monoclonal antibodies (mAbs) targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19. However, SARS-CoV-2 variants of concern (VOCs) profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use. Herein, we demonstrated mAb 35B5 efficiently neutralizes both wild-type (WT) SARS-CoV-2 and VOCs, including B.1.617.2 (delta) variant, in vitro and in vivo. Cryo-electron microscopy (cryo-EM) revealed that 35B5 neutralizes SARS-CoV-2 by targeting a unique epitope that avoids the prevailing mutation sites on RBD identified in circulating VOCs, providing the molecular basis for its pan-neutralizing efficacy. The 35B5-binding epitope could also be exploited for the rational design of a universal SARS-CoV-2 vaccine.

How silicate weathering responds to and regulates Earth’s climate remain controversial. This study suggests the primary control of temperature on weathering intensity globally and the temperature-weathering feedback may be stronger in cold Earth.

The assessment of seismic risk and the prevention of earthquake occurrences during reservoir operation present significant challenges in terms of accurate determination. This study aims to address this issue by developing a numerical model. The primary objective is to estimate the vulnerability of different fault types to reservoir impoundment. This model integrates essential parameters such as fault dip and the relative orientation between the reservoir and potential earthquakes, and it is structured within a risk framework using polar coordinates. Through comprehensive computations, we evaluate the alterations in elastic stress and fluid pore pressure resulting from water impoundment. This is achieved by employing a fully coupled two-dimensional poroelastic approach. Furthermore, our model incorporates relevant seismic data to enhance its accuracy. The findings of our study underscore that the critical factor lies in the fault’s precise positioning with respect to the reservoir. The risk associated with a fault is contingent upon both its location and its orientation, emphasizing the importance of these factors in determining hazardous zones.

Lipid metabolism and endoplasmic reticulum stress exhibit crosstalk in various cancer types, which are closely associated with the progression of colorectal cancer (CRC). This study constructs a prognostic signature based on lipid metabolism and endoplasmic reticulum stress-related genes (LERGs) for CRC patients, aiming to predict the prognosis and immune response. RNA sequencing and clinical data from the TCGA and GEO databases were analyzed to identify differentially expressed LERGs with prognostic relevance using univariate Cox regression. Subsequently, a risk model was developed using the LASSO regression. CRC patients were stratified into low-risk and high-risk groups based on risk scores, with the high-risk cohort demonstrating a poorer clinical prognosis in multiple databases. The risk model showed robust correlations with clinical features, gene mutations, and treatment sensitivity. Significant differences in immune cell infiltration and the expression of immune-related factors were also detected between risk groups, and elevated scores of cytokines and failure factors were detected in single-cell RNA sequencing analysis. This research indicates that lipid metabolism and endoplasmic reticulum stress in CRC are correlated with tumor progression, an immunosuppressive landscape, and alterations of drug sensitivity. The developed risk model can serve as a powerful prognostic tool, offering critical insights for refining clinical management and optimizing treatment in CRC patients.

Abstract There are still many difficulties in the recovery and long-term preservation of underwater archaeological artifacts, in situ preservation should be the first choice before further procedures are considered. However, the materials, preservation status, and preservation environment of underwater artifacts are diverse, resulting in many fragile artifacts facing difficult situations. In order to prevent serious damage, it is a safe protective strategy to preserve them in a controlled environment for a long time after excavation. Extraction and transfer of fragile cultural relics are vital parts of this strategy. Due to the complexity of the underwater environment and the vulnerability of fragile artifacts, safety in extraction and transfer still faces enormous challenges. Researchers have developed new materials and technologies to tackle this problem. This paper focuses on introducing and developing prospects to different preservation techniques for fragile artifacts from underwater sites.

Abstract Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Abstract Lignocellulosic biomass is composed of three major biopolymers: cellulose, hemicellulose and lignin. Analytical tools capable of quickly detecting both glycan and lignin deconstruction are needed to support the development and characterization of efficient enzymes/enzyme cocktails. Previously we have described nanostructure-initiator mass spectrometry-based assays for the analysis of glycosyl hydrolase and most recently an assay for lignin modifying enzymes. Here we integrate these two assays into a single multiplexed assay against both classes of enzymes and use it to characterize crude commercial enzyme mixtures. Application of our multiplexed platform based on nanostructure-initiator mass spectrometry enabled us to characterize crude mixtures of laccase enzymes from fungi Agaricus bisporus (Ab) and Myceliopthora thermophila (Mt) revealing activity on both carbohydrate and aromatic substrates. Using time-series analysis we determined that crude laccase from Ab has the higher GH activity and that laccase from Mt has the higher activity against our lignin model compound. Inhibitor studies showed a significant reduction in Mt GH activity under low oxygen conditions and increased activities in the presence of vanillin (common GH inhibitor). Ultimately, this assay can help to discover mixtures of enzymes that could be incorporated into biomass pretreatments to deconstruct diverse components of lignocellulosic biomass.

Islet transplantation to treat the late stage of type 1 diabetic patient (T1DM) has recently made inspiring success in clinical trials. However, most patients experience a decline in islet graft function in one to three years due to immune rejection. Although the mechanisms of immune cells, including macrophages, dendritic cells (DCs), neutrophils, natural killer cells (NKs), B cells, and T cells, that mediate immune rejection have been investigated, the overall characteristics of immune infiltrates in islet allografts and syngeneic grafts remain unclear. Single-cell RNA sequencing (scRNA-seq) has provided us with new opportunities to study the complexity of the immune microenvironment in islet transplants. In the present study, we used scRNA-seq to comprehensively analyze the immune heterogeneity in the mouse model of islet transplantation. Our data revealed T lymphocytes and myeloid cells as the main immune components of grafts 7 days post-islet transplantation, especially in allografts. Moreover, our results indicated that allogeneic islet cells were transformed into antigen-presenting cell-like cells with highly expressed MHC class I molecules and genes involved in MHC class I-mediated antigen presentation. This transformation may dramatically facilitate the interaction with cytotoxic CD8+ T cells and promote the destruction of islet allografts. Our study provides insight into the transcriptomics and diverse microenvironment of islet grafts and their impacts on immune rejection.

BackgroundAcinar cell carcinoma (ACC) is a rare pancreatic epithelial malignancy that poses a significant threat. However, there are few related clinical studies. The present study aimed to analyze the imaging and pathological features of ACC to provide a reference for better diagnosis and treatment planning.MethodsThirty-nine with ACC, referred to Qianfoshan Hospital, Qilu Hospital and Provincial Hospital in Shandong Province from December 2012 to December 2020, were enrolled. Their imaging and clinicopathological features were analyzed. They were followed up for 1 year, and Cox regression was used to analyze the factors affecting patient prognosis.ResultsACC was more common in the middle-aged and elderly and peaked at approximately 60 years. The clinical manifestations of the patients were mostly flatulence and upper abdomen pain. The tumor was located in the head of the pancreas in 19 cases, with an average size of 5.8 cm. We found nerve invasion and liver metastasis in one case each. 8 patients showed irregular amorphous tumor calcification on plain computed tomography and 5 showed high and low signals on T1- and T2-weighted images, respectively. Immunohistochemistry revealed 100.0% positive rates for CK, β-catenin, and Ki-67. Thirty-three patients underwent surgical resection, and the 2-year overall mortality rate was 25.6%. Cox analysis revealed that smoking was an independent risk factor affecting patient prognosis.ConclusionAn in-depth understanding of the imaging and clinicopathological features of ACC is conducive to better diagnosis and treatment planning for ACC and subsequent improvement in patient prognosis.

Abstract Background Lignin peroxidases catalyze a variety of reactions, resulting in cleavage of both β-O-4′ ether bonds and C–C bonds in lignin, both of which are essential for depolymerizing lignin into fragments amendable to biological or chemical upgrading to valuable products. Studies of the specificity of lignin peroxidases to catalyze these various reactions and the role reaction conditions such as pH play have been limited by the lack of assays that allow quantification of specific bond-breaking events. The subsequent theoretical understanding of the underlying mechanisms by which pH modulates the activity of lignin peroxidases remains nascent. Here, we report on combined experimental and theoretical studies of the effect of pH on the enzyme-catalyzed cleavage of β-O-4′ ether bonds and of C–C bonds by a lignin peroxidase isozyme H8 from Phanerochaete chrysosporium and an acid stabilized variant of the same enzyme. Results Using a nanostructure initiator mass spectrometry assay that provides quantification of bond breaking in a phenolic model lignin dimer we found that catalysis of degradation of the dimer to products by an acid-stabilized variant of lignin peroxidase isozyme H8 increased from 38.4% at pH 5 to 92.5% at pH 2.6. At pH 2.6, the observed product distribution resulted from 65.5% β-O-4′ ether bond cleavage, 27.0% Cα-C1 carbon bond cleavage, and 3.6% Cα-oxidation as by-product. Using ab initio molecular dynamic simulations and climbing-image Nudge Elastic Band based transition state searches, we suggest the effect of lower pH is via protonation of aliphatic hydroxyl groups under which extremely acidic conditions resulted in lower energetic barriers for bond-cleavages, particularly β-O-4′ bonds. Conclusion These coupled experimental results and theoretical explanations suggest pH is a key driving force for selective and efficient lignin peroxidase isozyme H8 catalyzed depolymerization of the phenolic lignin dimer and further suggest that engineering of lignin peroxidase isozyme H8 and other enzymes involved in lignin depolymerization should include targeting stability at low pH.

Abstract Reversing the highly immunosuppressive tumor microenvironment (TME) is essential to achieve long-term efficacy with cancer immunotherapy. Despite the impressive clinical response to checkpoint blockade in multiple types of cancer, only a minority of patients benefit from this approach. Here, we report that the oncolytic virus M1 induces immunogenic tumor cell death and subsequently restores the ability of dendritic cells to prime antitumor T cells. Intravenous injection of M1 disrupts immune tolerance in the privileged TME, reprogramming immune-silent (cold) tumors into immune-inflamed (hot) tumors. M1 elicits potent CD8+ T cell-dependent therapeutic effects and establishes long-term antitumor immune memory in poorly immunogenic tumor models. Pretreatment with M1 sensitizes refractory tumors to subsequent checkpoint blockade by boosting T-cell recruitment and upregulating the expression of PD-L1. These findings reveal the antitumor immunological mechanism of the M1 virus and indicated that oncolytic viruses are ideal cotreatments for checkpoint blockade immunotherapy.