PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I.

Gastric cancer (GC) is a common gastrointestinal system malignancy. PACSIN1 functions as an oncogene in various cancers. This study aims to investigate the potential of PACSIN1 as a target in GC treatment. Gene expression is determined by RT-qPCR, immunofluorescence staining, and immunohistochemistry assay. FISH is performed to determine the colocalization of PACSIN1 and the major histocompatibility complex (MHC-I). Cytokine release and cell functions are analyzed by flow cytometry. In vivo assays are also conducted. Histological analysis is performed using H&E staining. The results show that PACSIN1 is overexpressed in GC patients, especially in those with immunologically-cold tumors. A high level of PACSIN1 is associated with poor prognosis. PACSIN1 deficiency inhibits autophagy but increases antigen presentation in GC cells. Moreover, PACSIN1 deficiency inhibits the lysosomal fusion and selective autophagy of MHC-I, increases CD8 + T-cell infiltration, and suppresses tumor growth and liver metastasis in vivo. Additionally, PACSIN1 knockout enhances the chemosensitivity of cells to immune checkpoint blockade. In summary, PACSIN1 mediates lysosomal fusion and selective autophagy of MHC-I and suppresses antigen presentation and CD8 + T-cell infiltration, thus inhibiting antitumor immunity in GC.

Efficient Genetic Transformation and Suicide Plasmid-mediated Genome Editing System for Non-model Microorganism Erwinia persicina.

Erwinia persicina is a gram-negative bacterium that causes diseases in plants. Recently, E. persicina BST187 was shown to exhibit broad-spectrum antibacterial activity due to its inhibitory effects on bacterial acetyl-CoA carboxylase, demonstrating promising potential as a biological control agent. However, the lack of suitable genetic manipulation techniques limits its exploitation and industrial application. Here, we developed an efficient transformation system for E. persicina. Using pET28a as the starting vector, the expression cassette of the red fluorescent protein-encoding gene with the strong promoter J23119 was constructed and transformed into BST187 competent cells to verify the overexpression system. Moreover, suicide plasmid-mediated genome editing systems was developed, and lacZ was knocked out of BST187 genome by parental conjugation transfer using the recombinant suicide vector pKNOCK-sacB-km-lacZ. Therefore, both the transformation and suicide plasmid-mediated genome editing system will greatly facilitate genetic manipulations in E. persicina and promote its development and application. Key features • Our studies establish a genetic manipulation system for Erwinia persicina, providing a versatile tool for studying the gene function of non-model microorganisms. • Requires approximately 6-10 days to complete modification of a chromosome locus.

Rational modification of melatonin for broad-spectrum antifungal agents discovery.

Natural products, known for their environmental safety, are regarded as a significant basis for the modification and advancement of fungicides. Melatonin, as a low-cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential as an antifungal agent has not been fully explored. In this study, a series of melatonin derivatives targeting the mitogen-activated protein kinase (Mps1) protein of fungal pathogens were synthesized based on properties of melatonin, among which the trifluoromethyl-substituted derivative Mt-23 exhibited antifungal activity against seven plant pathogenic fungi, and effectively reduced the severity of crop diseases, including rice blast, Fusarium head blight of wheat and gray mold of tomato. In particular, its EC50 (5.4 µM) against the rice blast fungus Magnaporthe oryzae is only one-fourth that of isoprothiolane (22 µM), a commercial fungicide. Comparative analyzes revealed that Mt-23 simultaneously targets the conserved protein kinase Mps1 and lipid protein Cap20. Surface plasmon resonance assays showed that Mt-23 directly binds to Mps1 and Cap20. In this study, we provide a strategy for developing antifungal agents by modifying melatonin, and the resultant melatonin derivative Mt-23 is a commercially valuable, eco-friendly and broad-spectrum antifungal agent to combat crop disease.

Proline inhibits postharvest physiological deterioration of cassava by improving antioxidant capacity.

Cassava (Manihot esculenta Crantz), a crucial global tuber crop, encounters significant economic losses attributed to postharvest physiological deterioration (PPD). The PPD phenomenon in cassava is closely related to the accumulation of reactive oxygen species (ROS), and amino acids play a pivotal role in regulating signaling pathways and eliminating ROS. In this study, the storage performance of eight cassava varieties were conducted. Cassava cultivar SC5 showed the best storage performance among the eight cassava varieties, but the edible cassava cultivar SC9 performed much worse. Comparative analysis of free amino acids was conducted in eight cassava varieties, revealing changes in proline, aspartic acid, histidine, glutamic acid, threonine, and serine. Exogenous supplementation of these six amino acids was performed to inhibit PPD of SC9. Proline was confirmed as the key amino acid for inhibiting PPD. Treatment with optimal exogenous proline of 5 g/L resulted in a 17.9% decrease in the deterioration rate compared to untreated cassava. Accompanied by a decrease in H2O2 content and an increase in catalase, superoxide dismutase and ascorbate peroxidase activity. Proline treatment proved to be an effective approach to alleviate cell oxidative damage, inhibit PPD in cassava, and prolong shelf life.

PFKFB3 controls acinar IP3R-mediated Ca2+ overload to regulate acute pancreatitis severity.

Acute Pancreatitis (AP) is among the most common hospital gastrointestinal diagnosis; understanding the mechanisms underlying the severity of AP are critical for development of new treatment options for this disease. Here, we evaluate the biological function of phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in AP pathogenesis in two independent genetically engineered mouse models of AP. PFKFB3 is elevated in AP and severe AP (SAP) and knockout of Pfkfb3 abrogates the severity of alcoholic SAP (FAEE-SAP). Using a combination of genetic, pharmacological, and molecular studies we define the interaction of PFKFB3 with inositol 1,4,5-trisphosphate receptor (IP3R) as a key event mediating this phenomenon. Further analysis demonstrated that the interaction between PFKFB3 and IP3R promotes FAEE-SAP severity by altering intracellular calcium homeostasis in acinar cells. Together our results support a PFKFB3-driven mechanism controlling AP pathobiology and define this enzyme as a therapeutic target to ameliorate the severity of this dismal condition.

Inorganic Composition Modulation of Solid Electrolyte Interphase for Fast Charging Lithium Metal Batteries.

The solid electrolyte interphase (SEI) with lithium fluoride (LiF) is critical to the performance of lithium metal batteries (LMBs) due to its high stability and mechanical properties. However, the low Li ion conductivity of LiF impedes the rapid diffusion of Li ions in the SEI, which leads to localized Li ion oversaturation dendritic deposition and hinders the practical applications of LMBs at high-current regions (>3 C). To address this issue, a fluorophosphated SEI rich with fast ion-diffusing inorganic grain boundaries (LiF/Li3P) is introduced. By utilizing a sol electrolyte that contains highly dispersed porous LiF nanoparticles modified with phosphorus-containing functional groups, a fluorophosphated SEI is constructed and the presence of electrochemically active Li within these fast ion-diffusing grain boundaries (GBs-Li) that are non-nucleated is demonstrated, ensuring the stability of the Li || NCM811 cell for over 1000 cycles at fast-charging rates of 5 C (11 mA cm-2). Additionally, a practical, long cycling, and intrinsically safe LMB pouch cell with high energy density (400 Wh kg-1) is fabricated. The work reveals how SEI components and structure design can enable fast-charging LMBs.

Multi-Type Stochastic Resonances for Noise-Enhanced Mechanical, Optical, and Acoustic Sensing.

Stochastic resonance (SR) typically manifests in nonlinear systems, wherein the detection of a weak signal is bolstered by the addition of noise. Since its first discovery in a study of ice ages on Earth, various types of SRs have been observed in biological and physical systems and have been implemented in sensors to benefit from noise. However, a universally designed sensor architecture capable of accommodating different types of SRs has not been proposed, and the widespread applications of SRs in daily environments have not yet been demonstrated. Here, we propose a sensor architecture to simultaneously realize multi-type SRs and demonstrate their wide applications in mechanical, optical, and acoustic sensing domains. In particular, we find the coexistence of excitable SR and bistable SR in a sensor architecture composed of wirelessly coupled inductor-capacitor resonators connected to a nonlinearly saturable amplifier. In both types of SRs, adding noise to the system leads to a characteristic noise-enhanced signal-to-noise ratio (SNR). We further validate our findings through mechanical, optical, and acoustic sensing experiments and obtain noise-enhanced SNR by 9 dB, 3 dB, and 7 dB, respectively, compared to the standard methods devoid of SR integration. Our findings provide a general strategy to design various types of SRs and pave the way for the development of a distinctive class of sensors leveraging environmental noise, with potential applications ranging from biomedical devices to ambient sensing.

Drivers of natural gas use in U.S. residential buildings.

Natural gas is the primary fuel used in U.S. residences, yet little is known about its consumption patterns and drivers. We use daily county-level gas consumption data to assess the spatial patterns of the relationships and the sensitivities of gas consumption to outdoor air temperature across U.S. households. We fitted linear-plus-plateau functions to daily gas consumption data in 1000 counties, and derived two key coefficients: the heating temperature threshold (Tcrit) and the gas consumption rate change per 1°C temperature drop (Slope). We identified the main predictors of Tcrit and Slope (like income, employment rate, and building type) using interpretable machine learning models built on census data. Finally, we estimated a potential 2.47 million MtCO2 annual emission reduction in U.S. residences by gas savings due to household insulation improvements and hypothetical behavioral change toward reduced consumption by adopting a 1°C lower Tcrit than the current value.

Size effect of mesoporous silica nanoparticles on regulating the immune effect of oral influenza split vaccine.

Mucosal immunization is a powerful weapon against viral infection. In this paper, large pore mesoporous silica nanoparticles (LMSN) with different particle sizes were synthesized for loading influenza split vaccine (SV) to explore the effect of nanoparticle sizes on mucosal immunization and adjuvant efficacy. Interestingly, it was found that among the three particle sizes of nanoparticles, only LMSN-M with around 250 nm could significantly enhance the mucosal immune effect of SV, possessing adjuvant effect. The results indicated that particle size affected the adjuvant effect of LMSN. There was no apparent difference in vaccine loading capacity of LMSN with different particle sizes, but the release of SV depended on the pore length of LMSN. The adjuvant effect of LMSN-M was attributed to its higher cellular uptake performance, intestine absorption and transport efficiency, and the ability to stimulate the maturation of dendritic cells. Simultaneously, compared with LMSN-S and LMSN-L, the more retention of LMSN-M in mesenteric lymph nodes increased the chance of interaction between vaccine and immune system, resulting in the enhanced immunity. This is the first time to study the impact of particle size of LMSN adjuvant on improving mucosal immunity of oral influenza vaccine, and the present work provides a scientific reference for adjuvant design of oral vaccine.

Research on differential game of platform corporate social responsibility governance strategy considering user and public scrutiny.

The development of digital technology and the sharing economy has extended corporations' innovative activities beyond the corporation's boundaries, so it has become more urgent to govern the lack of social responsibility and alienation of platform corporations from the perspective of social agents. First, the platform's CSR classification and social responsibility governance's main content are analyzed in this research. Then, this study uses government agencies, platform corporations, users, and the public as governance subjects and compares governance decisions with and without public and user oversight. Finally, the optimal balance strategy for each governing subject, the optimal trajectory of governance volume, and the trajectory of total revenue are obtained. The study found that: 1) Public and user supervision can improve the governance volume while encourage the governance motivation of government agencies and platform corporations. 2) The level of user supervision effort has a greater impact on the total governance revenue than public supervision. 3) The revenue of the system and the governance volume are greater in a centralized decision-making process, indicating that those involved should co-operate in governance based on the principle of mutual benefit. 4) The platform corporation has an incompatible but unified relationship between its social duty and financial success.

Photoinduced Pd-Catalyzed Enantioselective Carboamination of Dienes via Aliphatic C-H Bond Elaboration.

Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C-H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)-H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)-H bearing partners.

A Task-guided, Implicitly-searched and Metainitialized Deep Model for Image Fusion.

Image fusion plays a key role in a variety of multi-sensor-based vision systems, especially for enhancing visual quality and/or extracting aggregated features for perception. However, most existing methods just consider image fusion as an individual task, thus ignoring its underlying relationship with these downstream vision problems. Furthermore, designing proper fusion architectures often requires huge engineering labor. It also lacks mechanisms to improve the flexibility and generalization ability of current fusion approaches. To mitigate these issues, we establish a Task-guided, Implicit-searched and Meta-initialized (TIM) deep model to address the image fusion problem in a challenging real-world scenario. Specifically, we first propose a constrained strategy to incorporate information from downstream tasks to guide the unsupervised learning process of image fusion. Within this framework, we then design an implicit search scheme to automatically discover compact architectures for our fusion model with high efficiency. In addition, a pretext meta initialization technique is introduced to leverage divergence fusion data to support fast adaptation for different kinds of image fusion tasks. Qualitative and quantitative experimental results on different categories of image fusion problems and related downstream tasks (e.g., visual enhancement and semantic understanding) substantiate the flexibility and effectiveness of our TIM.

Role of Type VI secretion system in pathogenic remodeling of host gut microbiota during Aeromonas veronii infection.

Intestinal microbial disturbance is a direct cause of host disease. The bacterial Type VI secretion system (T6SS) often plays a crucial role in the fitness of pathogenic bacteria by delivering toxic effectors into target cells. However, its impact on the gut microbiota and host pathogenesis is poorly understood. To address this question, we characterized a new T6SS in the pathogenic Aeromonas veronii C4. First, we validated the secretion function of the core machinery of A. veronii C4 T6SS. Second, we found that the pathogenesis and colonization of A. veronii C4 is largely dependent on its T6SS. The effector secretion activity of A. veronii C4 T6SS not only provides an advantage in competition among bacteria in vitro, but also contributes to occupation of an ecological niche in the nutritionally deficient and anaerobic environment of the host intestine. Metagenomic analysis showed that the T6SS directly inhibits or eliminates symbiotic strains from the intestine, resulting in dysregulated gut microbiome homeostasis. In addition, we identified three unknown effectors, Tse1, Tse2, and Tse3, in the T6SS, which contribute to T6SS-mediated bacterial competition and pathogenesis by impairing targeted cell integrity. Our findings highlight that T6SS can remodel the host gut microbiota by intricate interplay between T6SS-mediated bacterial competition and altered host immune responses, which synergistically promote pathogenesis of A. veronii C4. Therefore, this newly characterized T6SS could represent a general interaction mechanism between the host and pathogen, and may offer a potential therapeutic target for controlling bacterial pathogens.

Machine-learning model for the prediction of acute orthostatic hypotension after levodopa administration.

BACKGROUND: Levodopa could induce orthostatic hypotension (OH) in Parkinson's disease (PD) patients. Accurate prediction of acute OH post levodopa (AOHPL) is important for rational drug use in PD patients. Here, we develop and validate a prediction model of AOHPL to facilitate physicians in identifying patients at higher probability of developing AOHPL. METHODS: The study involved 497 PD inpatients who underwent a levodopa challenge test (LCT) and the supine-to-standing test (STS) four times during LCT. Patients were divided into two groups based on whether OH occurred during levodopa effectiveness (AOHPL) or not (non-AOHPL). The dataset was randomly split into training (80%) and independent test data (20%). Several models were trained and compared for discrimination between AOHPL and non-AOHPL. Final model was evaluated on independent test data. Shapley additive explanations (SHAP) values were employed to reveal how variables explain specific predictions for given observations in the independent test data. RESULTS: We included 180 PD patients without AOHPL and 194 PD patients with AOHPL to develop and validate predictive models. Random Forest was selected as our final model as its leave-one-out cross validation performance [AUC_ROC 0.776, accuracy 73.6%, sensitivity 71.6%, specificity 75.7%] outperformed other models. The most crucial features in this predictive model were the maximal SBP drop and DBP drop of STS before medication (ΔSBP/ΔDBP). We achieved a prediction accuracy of 72% on independent test data. ΔSBP, ΔDBP, and standing mean artery pressure were the top three variables that contributed most to the predictions across all individual observations in the independent test data. CONCLUSIONS: The validated classifier could serve as a valuable tool for clinicians, offering the probability of a patient developing AOHPL at an early stage. This supports clinical decision-making, potentially enhancing the quality of life for PD patients.

Advanced detection tools in food fraud: A systematic review for holistic and rational detection method based on research and patents.

Modern food chain supply management necessitates the dire need for mitigating food fraud and adulterations. This holistic review addresses different advanced detection technologies coupled with chemometrics to identify various types of adulterated foods. The data on research, patent and systematic review analyses (2018-2023) revealed both destructive and non-destructive methods to demarcate a rational approach for food fraud detection in various countries. These intricate hygiene standards and AI-based technology are also summarized for further prospective research. Chemometrics or AI-based techniques for extensive food fraud detection are demanded. A systematic assessment reveals that various methods to detect food fraud involving multiple substances need to be simple, expeditious, precise, cost-effective, eco-friendly and non-intrusive. The scrutiny resulted in 39 relevant experimental data sets answering key questions. However, additional research is necessitated for an affirmative conclusion in food fraud detection system with modern AI and machine learning approaches.

Comparison of vonoprazan-based dual therapy with vonoprazan-based bismuth quadruple therapy for treatment-naive patients with Helicobacter pylori infection: A propensity score matching analysis.

Vonoprazan, a novel acid suppressant and the first potassium-competitive acid blocker, has the potential to enhance the eradication rate of Helicobacter pylori due to its robust acid-suppressing capacity. This study aimed to compare the efficacy of vonoprazan-based dual therapy (vonoprazan-amoxicillin, VA) with vonoprazan-based bismuth quadruple therapy (VBQT) as a first-line treatment for H pylori infection. This retrospective single-center non-inferiority study was conducted in China. Treatment-naive H pylori-positive patients aged 18 to 80 received one of the 2 treatment regimens at our center. The VA group received vonoprazan 20 mg twice daily and amoxicillin 1000 mg 3 times daily for 14 days, whereas the VBQT group received vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. The eradication rate was evaluated 4 to 6 weeks after treatment using the carbon-13/14 urea breath test. Propensity score matching was used to analyze eradication rates, adverse events (AEs), and patient compliance between the 2 groups. Initially, 501 patients were included, and after propensity score analysis, 156 patients were selected for the study. Intention-to-treat analysis showed eradication rates of 87.2% (95% CI, 79.8-94.6%) for the VA group and 79.5% (95% CI, 70.5-88.4%) for the VBQT group (P = .195). Per-protocol analysis demonstrated rates of 94.4% (95% CI, 89.2-99.7%) for the VA group and 96.8% (95% CI, 92.4-100%) for the VBQT group (P = .507). Non-inferiority was confirmed between the 2 groups, with P values < .025. The VA group showed a lower rate of AEs (10.3% vs 17.9%, P = .250) compared to the VBQT group. There were no significant differences in patient compliance between the 2 groups. In treatment-naive patients with H pylori infection, both the 14-day VA and VBQT regimens demonstrated comparable efficacy, with excellent eradication rates. Moreover, due to reduced antibiotic usage, lower rate of AEs, and lower costs, VA dual therapy should be prioritized.

Vonoprazan-amoxicillin dual therapy with different amoxicillin dosages for treatment-naive patients of Helicobacter pylori infection in China: a prospective, randomized controlled study.

BACKGROUND: The vonoprazan (VPZ)-amoxicillin (AMO) dual therapy (VA) demonstrates a satisfactory eradication rate for Helicobacter pylori (H. pylori ). However, the optimal dosage of AMO in this regimen remains uncertain. The objective of this study is to investigate the efficacy of different doses of AMO in the VA regimen for first-line treatment of H. pylori infection. METHODS: A total of 192 treatment-naive H. pylori -infected patients were randomly assigned to one of three groups: low-dose VA (LD-VA: VPZ 20 mg b.i.d + AMO 750 mg t.i.d), moderate-dose VA (MD-VA:VPZ 20 mg b.i.d + AMO 1000 mg t.i.d), and high-dose VA (HD-VA: VPZ 20 mg b.i.d + AMO 1250 mg t.i.d). All groups received 14 days of treatment. The study evaluated and compared the eradication rates, adverse events (AEs), and patient compliance among the three groups. RESULTS: Eradication rates for LD-VA, MD-VA, and HD-VA were 76.6% (49/64), 79.7% (51/64), and 84.4% (54/64), respectively, as determined by intention-to-treat analysis; 90.6% (48/53), 94.3% (50/53), and 98.1% (53/54) according to per-protocol analysis; 89.1% (49/55), 94.4% (51/54), and 96.4% (54/56) with modified intention-to-treat analysis (all P  > 0.05). Although not statistically significant, numerically higher eradication rates were observed with the higher dose AMO VA regimen. There were no statistically significant differences in the incidence of AEs and compliance among the three VA regimens. CONCLUSION: Fourteen-day VA regimens with AMO doses exceeding 2 g/day demonstrated satisfactory eradication rates. HD-VA therapy is potentially the most effective regimen. Large-sample clinical trials are required to further validate these findings.

A comparison of endothelial cell growth on commercial coronary stents with and without laser surface texturing.

Complete endothelialisation of coronary stents is an important determinant of future thrombotic complications following coronary stenting. Stent surface texture is an important factor that influences endothelial cell growth. With the emergence of second and third generation coronary stents, is limited comparative data describing endothelial cell growth in contemporary stent platforms, and limited data available on approaches used to rapidly modify the surfaces of commercial coronary stents to improve endothelialisation. In this study we have determined the in vitro proliferation of the primary human coronary artery endothelial cells on the commonly used 4 types of commercial coronary stents and found that the inner surface of BioMatrix drug-eluting stents (DES), after eliminating of the polymer and drug coating, had significantly higher endothelial cell proliferation compared to that of other bare metal stents (BMS): Multi-Link8, Integrity and Omega. The surfaces of the 3 types of BMS which are smooth, displayed similar endothelial cell proliferation, suggesting the importance of surface features in manipulating endothelial cell growth. Laser surface texturing was used to create micro/nano patterns on the stents. The laser treatment has significantly increased endothelial proliferation on the inner surfaces of all 4 types of stents, and Multi-Link8 stents displayed the highest (>100%) improvement. The laser textured BioMatrix stents had the highest absolute number of endothelial cells growth. Our results provided useful information in the endothelialisation potential for the commonly used commercial coronary stents and suggested a potential future application of laser surface bioengineering to coronary stents for better biocompatibility of the device.

Effects of predictive nursing interventions on pressure ulcer in older bedridden patients: A meta-analysis.

To evaluate the effect of predictive nursing interventions on pressure ulcers in elderly bedridden patients by meta-analysis. Applied computer searches of PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases for randomised controlled trials (RCTs) on the effect of predictive nursing in preventing pressure ulcers in elderly bedridden patients from the database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on inclusion and exclusion criteria. Stata 17.0 software was utilised for data analysis. Eighteen RCTs involving 6504 patients were finally included. The analysis revealed the implementation of predictive nursing interventions had a significant advantage in reducing the incidence of pressure ulcers in elderly bedridden patients compared with conventional nursing (odds ratio [OR] = 0.20, 95% confidence interval [CI]: 0.15-0.28, p < 0.001), while the patients' satisfaction with nursing care was higher (OR = 3.70, 95% CI: 2.99-4.57, p < 0.001). This study shows that the implementation of a predictive nursing interventions for elderly bedridden patients can effectively reduce the occurrence of pressure ulcers and significantly improve patients' satisfaction with nursing care, which is worthy of clinical promotion and application.