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Abstract High signal-to-noise ratio (SNR) seismic waveform data are conductive to various studies in seismology. Seismic denoising aims to enhance SNR by eliminating additive noise through signal processing while preserving important features of the seismic signal. Conventional parametric seismic denoising methods often require selecting appropriate parameters to achieve optimal results, which may be limiting when dealing with various types and scales of seismic data. Here, we develop an adaptive parameter-free denoising method by combining general cross-validation (GCV) thresholding and pixel connectivity in synchrosqueezed (SS) domain. In this denoising framework, the synchrosqueezed continuous wavelet transform (SS-CWT) is first applied to obtain a high-resolution time–frequency representation. Then, the GCV approach, which allows for choosing the (nearly) optimal threshold without relying on any prior knowledge about the noise level, is employed to attenuate most of the low-energy noise. After that, the relatively isolated high-energy residual noise remaining in the SS-CWT spectrum is removed using pixel connectivity thresholding. Finally, the inverse SS-CWT is applied to the thresholded spectrum to obtain the denoised seismic record. As the thresholds for GCV and pixel connectivity are derived from the spectrum characteristics of the data being analyzed, the proposed denoising approach is highly adaptive and parameter-free. We demonstrate the effectiveness and versatility of the proposed denoising framework using synthetic data and real seismic data from diverse monitoring scenarios, including land, ocean, and emerging distributed acoustic sensing (DAS). The results indicate that the method is a stable and efficient tool for seismic data denoising. Graphical Abstract

Abstract The current study aimed to investigate the status of genes with prognostic DNA methylation sites in bladder cancer (BLCA). We obtained bulk transcriptome sequencing data, methylation data, and single-cell sequencing data of BLCA from public databases. Initially, Cox survival analysis was conducted for each methylation site, and genes with more than 10 methylation sites demonstrating prognostic significance were identified to form the BLCA prognostic methylation gene set. Subsequently, the intersection of marker genes associated with epithelial cells in single-cell sequencing analysis was obtained to acquire epithelial cell prognostic methylation genes. Utilizing ten machine learning algorithms for multiple combinations, we selected key genes (METRNL, SYT8, COL18A1, TAP1, MEST, AHNAK, RPP21, AKAP13, RNH1) based on the C-index from multiple validation sets. Single-factor and multi-factor Cox analyses were conducted incorporating clinical characteristics and model genes to identify independent prognostic factors (AHNAK, RNH1, TAP1, Age, and Stage) for constructing a Nomogram model, which was validated for its good diagnostic efficacy, prognostic prediction ability, and clinical decision-making benefits. Expression patterns of model genes varied among different clinical features. Seven immune cell infiltration prediction algorithms were used to assess the correlation between immune cell scores and Nomogram scores. Finally, drug sensitivity analysis of Nomogram model genes was conducted based on the CMap database, followed by molecular docking experiments. Our research offers a reference and theoretical basis for prognostic evaluation, drug selection, and understanding the impact of DNA methylation changes on the prognosis of BLCA.

In order to investigate the effects of fermented oyster enzymatic hydrolysates on the quality of oyster juice, this study firstly identified oyster species suitable for the processing of oyster juice and established an exclusive sensory descriptive library for oyster juice. And then, through single-factor experimental analysis based on sensory scores and amino acid nitrogen content, the optimal fermentation conditions were determined. The free amino acids, volatile flavor components, and sensory properties were compared between unfermented oyster hydrolysates, fermented oyster hydrolysates, and seasoning fermented oyster hydrolysates. The results showed that Rushan oysters (Crassostrea gigas) were selected for oyster juice processing and an exclusive sensory descriptive library was developed. Lactiplantibacillus pentosus was vaccinate as the fermenting agent. Optimum fermentation condition was at 37 ℃ with the inoculum of 7% for 3 h. Under the optimized conditions, both the amino nitrogen content and flavor were significantly improved. The optimal flavoring conditions for the fermented oyster hydrolysates involved high temperature and pressure treatment (100 kPa, 121 ℃, 20 min) with 8% glucose addition and 2% salt addition, followed by volume concentration to 50% of the original. These conditions resulted in further enhancement of amino nitrogen content with the content of 1.06±0.03 g/100 g and aroma. Additionally, fermentation led to a significant increase (P

Background: Endoscopy is important for the diagnosis and treatment of acute upper gastrointestinal bleeding (AUGIB), especially acute variceal bleeding (AVB), in liver cirrhosis. However, the optimal timing of endoscopy remains controversial, primarily because the currently available evidence is of poor quality, and the definition of early endoscopy is also very heterogeneous among studies. Herein, a multicenter randomized controlled trial (RCT) is performed to explore the impact of the timing of endoscopy on the outcomes of cirrhotic patients with AVB. Methods: A total of 368 cirrhotic patients presenting with AUGIB who are highly suspected to be from AVB will be enrolled. They will be stratified according to the severity of liver function and clinical presentation at admission and then randomly assigned at a 1:1 ratio into early (within 12 h after admission) and delayed (within 12–24 h after admission) endoscopy groups within each stratum. The primary outcomes include the rates of 5-day failure to control bleeding after admission and 6-week rebleeding. The secondary outcomes include 6-week mortality and incidence of adverse events. Conclusion: Considering existing evidence originates from non-randomized studies, this RCT will provide high-quality evidence to uncover whether cirrhotic patients with AVB should undergo early endoscopy to control bleeding and improve survival. Trial registration: ClinicalTrials.gov identifier: NCT06031402.

Abstract Using the flexibility and diversity of material and structure designs possible with 3D printing fiber technology, an all‐solid photonic crystal fiber (PCF) is fabricated using borate (B2O3) doping. The geometry, material, and optical properties of this 3D printed PCF are characterized and analyzed using optical microscopy, scanning electron microscopy (SEM), fiber index profilometry, and Fourier transform infrared (FTIR) microscopy. Analysis demonstrates that B2O3 doped in fabricated PCF has experienced evaporation leading to mass loss during drawing. In addition, there is no observable difference between the structure of substrate silica (SiO2) and the SiO2 nanoparticles. However, microdomain differences may explain enhanced reflectance. Furthermore, a Mach–Zehnder interferometer (MZI) sensor is constructed with this 3D printed solid PCF and applied to temperature, refractive index, tensile force, and bending sensing. The specially designed 3D printed PCF has maximum temperature sensitivity up to Δλ/ΔT ≈0.075 nm °C−1. When immersed in 76.34 wt.% glycerol‐water solution, the sensitivity can be further improved. These results demonstrate that 3D printing fiber technology enables the custom fabrication of highly sensitive optical fiber sensors, increasing opportunities for the development of diverse and flexible sensors and devices for future internet‐of‐things (IoT) applications.

The pore throat size, structure distribution, and lithology of porous media in gas reservoirs are varied, and the gas-water two-phase seepage law is complex, making it difficult to describe the seepage model. Newton's law of motion is a basic law of motion in classical mechanics, and its application in gas-water two-phase seepage modeling is an innovative practice of classical mechanics in seepage mechanics systems. Based on Newton's three laws of motion, a gas-water two-phase seepage model was established from the force analysis of fluid, and the relationship between velocity and pressure difference, pipe radius, water film thickness, viscosity, etc. was derived under the condition that the model reached a stable state, i.e., force balance. The relationship is referred to as the steady-state model. Subsequently. the equivalent permeability representation model was derived based on the steady-state model to calculate the permeability of rock samples with different channel distribution characteristics. The results were consistent with the measured values, and there is a good correspondence between channel distribution characteristics and permeability. The relative permeability calculation method was established based on the steady-state model and capillary pressure curve. The obtained relative permeability curve aligned with the two-phase seepage law and coincides with the relative permeability curve obtained by Poiseuille's law. Finally, a new productivity equation was derived based on the steady-state model, and the Inflow Performance Relationship (IPR) curve calculated by the gas well example was consistent with the traditional equation. The research results were based on the force analysis of fluid in porous media and fundamentally explored the law of fluid flow. The derived seepage model can be used to calculate reservoir permeability, the gas-water relative permeability curve, and gas well productivity analysis and to effectively guide gas reservoir development. The study was a successful application of the basic theory of mechanics in gas-water two-phase seepage in gas reservoirs.

Summary: Stapokibart (CM310) is a humanized IL-4Rα monoclonal antibody currently undergoing phase 3 trials for type 2 inflammatory diseases. In contrast to dupilumab, which bound exclusively to human IL-4Rα, stapokibart demonstrated cross-species reactivity to IL-4Rα from human, cynomolgus monkey, and rat. Stapokibart exhibited comparable blocking activity to dupilumab. Epitope mapping revealed that stapokibart bound to distinct sites on IL-4Rα compared to dupilumab. In vitro assays showed that stapokibart was comparable or numerically superior in blocking IL-4Rα-mediated signaling compared to dupilumab. In vivo studies further demonstrated that stapokibart effectively inhibited the progression of type 2 inflammation. Pharmacokinetic studies revealed a circulating half-life of approximately 298–351 h in cynomolgus monkeys and 55–142 h in rats for stapokibart. Toxicity studies indicated a favorable safety profile in cynomolgus monkeys and rats. The preclinical evaluation of stapokibart supports its clinical development.

Abstract Background The adoption of digitization has emerged as a new trend in the advancement of healthcare systems. To ensure high-quality care, nurses should possess sufficient skills to assist in the digital transformation of healthcare practices. Suitable tools have seldom been developed to assess nurses’ skills in digital applications. This study aimed to develop the Nursing Digital Application Skill Scale (NDASS) and test its psychometric properties. Methods The Nursing Digital Application Skill Scale was developed in three phases. In Phase 1, an item pool was developed based on previous literature and the actual situation of nursing work. Phase 2 included 14 experts’ assessment of content validity and a focus group interview with 30 nurses to pretest the scale. In phase 3, 429 registered nurses were selected from March to June 2023, and item analysis, exploratory factor analysis, and confirmatory factor analysis were used to refine the number of items and explore the factor structure of the scale. Additionally, reliability was determined by internal consistency and test-retest reliability. Results The final version of the NDASS consisted of 12 items. The content validity index of NDASS reached 0.975 at an acceptable level. The convergent validity test showed that the average variance extracted value was 0.694 (> 0.5) and the composite reliability value was 0.964 (> 0.7), both of which met the requirements. The principal component analysis resulted in a single-factor structure explaining 74.794% of the total variance. All the fitting indices satisfied the standard based upon confirmatory factor analyses, indicating that the single-factor structure contributed to an ideal model fit. The internal consistency appeared high for the NDASS, reaching a Cronbach’s alpha value of 0.968. The test-retest reliability was 0.740, and the split-half coefficient was 0.935. Conclusion The final version of the NDASS, which possesses adequate psychometric properties, is a reliable and effective instrument for nurses to self-assess digital skills in nursing work and for nursing managers in designing nursing digital skill training.

Abstract Introduction Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2 years with mild to moderate AD. Methods We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28 days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator’s Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. Results Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: −66.34 [95% (confidence interval) CI −71.55 to −61.12] vs. −50.18 [95% CI −58.02 to −42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4–51.1] vs. 33.4% [95% CI 22.5–44.2]) and ISGA success (31.7% [95% CI 24.3–39.0] vs. 21.5% [95% CI 12.1–30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: −1.98 [95% CI −2.34 to −1.62] vs. −1.08 [95% CI −1.63 to −0.53]). No new safety signals were observed. Conclusion Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2 years with mild to moderate AD. Trial Registration ClinicalTrials.gov, NCT04360187.

Abstract For expanding the amplitude-frequency response range of the differential cross-phase multiply (DCM) algorithm in the φ-OTDR system, a temporal spline interpolation (TSI) method is proposed to pre-process Rayleigh backscattering (RBS) signals. Through the TSI method, the discrete temporal signals characterizing RBS traces are subjected to interpolation, facilitating a reduction in differential approximation errors. This, in turn, establishes a heightened level of precision in phase demodulation, especially relevant across extensive sensing distances. By comparing the recovered time-domain waveforms and the corresponding power spectral densities without and with the TSI, the above improvement effect has been experimentally validated by utilizing the TSI. The results show that, with the TSI, the amplitude-frequency response range of the DCM algorithm is enlarged by 2.78 times, and the new relationship among f pulse, f, and D under the root mean square error (RMSE) tolerance less than 0.1 can be expressed as 1.9(D+1)f ≤ f pulse. This contribution underscores a substantial advancement in the capabilities of the DCM algorithm, holding promise for refined performance in optical fiber sensing applications.

In order to overcome the problems existed in the construction process of complex giant system of smart mine, the overall technical framework of smart mine construction was proposed, and a detailed description was made from the aspects of smart mine system model construction, underground space reconstruction and model dynamic update, machine vision measurement technology, radio frequency explosion-proof test method of gas environment, mine safety closed-loop control system, smart mine standard system, etc. The smart mine was divided into information sensing support layer, edge computing layer, cloud data center, multi-type network, intelligent mine production management and control platform, intelligent mine production system and intelligent mine operation and maintenance management system. The smart mine technology architecture based on the deep integration of multiple systems was built. Based on the knowledge map and information extraction of smart mine, a smart mine system model driven by data innovation, based on communication network and centered on data computing power was constructed. A 3D visual space model based on machine vision perception information and supplemented by other perception information was constructed, and a 3D vision and spatial reconstruction framework of mine underground scene was proposed to realize the reconstruction and dynamic update of the 3D space of underground mine. Based on machine vision technology, the identification algorithm of downhole equipment position and coal-rock interface was developed to realize the simultaneous aerial measurement of fully mechanized mining equipment group and coal-rock interface. The limitations and shortcomings of the current explosion-proof standards on the power of 5G base stations in the underground gas environment were discussed, and a special test device for radio-frequency electromagnetic energy explosion-proof was designed and developed, which provides a method for reference to improve the power threshold of underground 5G base stations. The technical framework of mine disaster closed-loop management and control system, which integrates comprehensive perception of disaster information, independent decision-making of prevention and control plan, and coordinated control of prevention and control equipment, was proposed to realize advanced prediction and early warning and coordinated prevention and control of underground disasters. The framework of intelligent coal mine standard system was constructed, the typical cases of intelligent construction of coal mine and metal mine in China were analyzed, and the development trend and suggestions of intelligent mine construction were put forward.

Abstract Objective The current study used a composite outcome to investigate whether applying the ERAS protocol would enhance the recovery of patients undergoing laparoscopic total gastrectomy (LTG). Exposures Laparoscopic total gastrectomy and perioperative interventions were the exposure. An ERAS clinical pathway consisting of 14 items was implemented and assessed. Patients were divided into either ERAS-compliant or non-ERAS-compliant group according the adherence above 9/14 or not. Main outcomes and measures The primary study outcome was a composite outcome called ‘optimal postoperative recovery’ with the definition as below: discharge within 6 days with no sever complications and no unplanned re-operation or readmission within 30 days postoperatively. Univariate logistic regression analysis and multivariate logistic regression analysis were used to model optimal postoperative recovery and compliance, adjusting for patient-related and disease-related characteristics. Results A total of 252 patients were included in this retrospective study, 129 in the ERAS compliant group and 123 in the non-ERAS-compliant group. Of these, 79.07% of the patients in ERAS compliant group achieved optimal postoperative recovery, whereas 61.79% of patients in non-ERAS-compliant group did (P = 0.0026). The incidence of sever complications was lower in the ERAS-compliant group (1.55% vs. 6.5%, P = 0.0441). No patients in ERAS compliant group had unplanned re-operation, whereas 5.69% (7/123) of patients in non-ERAS-compliant group had (p = 0.006). The median length of the postoperative hospital stay was shorter in the in the ERAS compliant group (5.51 vs. 5.68 days, P = 0.01). Both logistic (OR 2.01, 95% CI 1.21–3.34) and stepwise regression (OR 2.07, 95% CI 1.25–3.41) analysis showed that high overall compliance with the ERAS protocol facilitated optimal recovery in such patients. In bivariate analysis of compliance for patients who had an optimal postoperative recovery, carbohydrate drinks (p = 0.0196), early oral feeding (P = 0.0043), early mobilization (P = 0.0340), and restrictive intravenous fluid administration (P

Background Helicobacter pylori (H. pylori) has infected approximately 4.4 billion individuals worldwide. The known virulence genes and the existing H. pylori typing methods have not been shown to have a recognized correlation with its infectivity. The aim of this study was to elucidate the relationships among known important virulence genes, coccoid transformation, and cytotoxicity of H. pylori isolated from individuals with different clinical diseases to provide guidance for the development of new virulence typing methods for H. pylori.Methods The known important virulence genes of 35 H. pylori strains were identified by whole-gene next-generation sequencing (WGS) and polymerase chain reaction (PCR). The chronological changes in the proportion of coccoid forms of H. pylori and their ultramicroscopic structures were observed chronologically using transmission electron microscopy. Human gastric mucosal epithelial cells (GES-1) were infected with H. pylori strains in vitro to evaluate cytotoxicity of H. pylori.Results There were no significant correlations among the known important virulence genes, coccoid transformation and cytotoxicity of H. pylori isolated from patients with different clinical diseases. We developed a new virulence classification based on the defensive and offensive abilities of H. pylori.Conclusions Coccoid transformation and virulence are two independent characteristics of H. pylori that reflect its defensive and offensive abilities, respectively. These two abilities work synergistically, warranting the construction of a new virulence typing method for H. pylori. However, the correlation between the new virulence classification and pathogenic ability still needs to be further verified.

AbstractBackground Understanding the patient journey is important to optimize care for patients with atopic dermatitis (AD) and overcome challenges in diagnosis and management.Objective To explore patient and caregiver perspectives regarding their experience with AD.Methods Patients and caregivers of patients with AD completed a pre-meeting survey and were invited to join an advisory board meeting in their country (China, Hong Kong, Ireland, Japan and Lebanon) to discuss the survey results. Data were analyzed descriptively.Results The survey included 31 participants (patients and caregivers) from Hong Kong (n = 7), China (n = 7), Ireland (n = 6), Japan (n = 6) and Lebanon (n = 5). The most challenging factors in the AD journey were management of symptoms before a confirmed diagnosis (68%), sudden recurrence of flares or worsening of symptoms (68%) and lifestyle changes (52%). In terms of overall AD management, 35% of participants indicated that AD was managed well, 23% had a clear treatment plan and 19% were generally satisfied with disease management. A collaborative relationship with healthcare professionals was favored.Conclusion A holistic assessment of AD includes understanding patient and caregiver preferences, needs, experiences and disease perceptions. Addressing the identified gaps may improve the management of AD.

ABSTRACTCampylobacter upsaliensis was the most common Campylobacter species in pets’ gastrointestinal tracts and has been isolated from patients with bacteremia, hemolytic-uremic syndrome, spontaneous abortion, and Guillain-Barré syndrome. However, the genetic characteristics and the full extent of its significance as a human pathogen remain to be fully understood. This study involved an investigation for genomic analysis of 154 strains from different sources and additional antimicrobial resistance profiles of 26 strains for this species. The genomes contained 1,558–1,971 CDS and the genome sizes were estimated to vary from 1.53 Mb to 1.86 Mb, with an average GC content of 34.71%. The entire analyzed genomes could be divided into three clades (A, B, and C) based on ANI and phylogenomic analysis. Significantly, nearly all strains in Clade B were isolated from patient samples, and the virulence-related sequences FlgD, GmhA, and CdtC might serve as determining factors for the classification of Clade B. Half of the tested isolates had MIC values over 64 μg mL−1 for nalidixic acid, gentamicin, and streptomycin. Isolates from pets in China carried more resistant elements in the genomes. This study both provided a comprehensive profile of C. upsaliensis for its genomic features and suggested some pathogenic agents for human infection with this species.

Purpose: Systemic lupus erythematosus (SLE) is largely caused by B cell dysfunction. JunD is an activator protein 1 family protein that has been linked to the regulation of apoptotic and proliferative activities. However, the precise mechanism(s) by which JunD functions remains to be fully elucidated. Accordingly, this study aimed to clarify the functional importance of JUND gene expression in SLE, with further analyses of the functional role that JunD plays as a regulator of B cell proliferation and immune function. Methods: Reverse transcriptase quantitative polymerase chain reaction techniques were used to analyze JunD expression in B cells of patients with SLE and healthy subjects. Cell Counting Kit-8 (CCK-8) assays and flow cytometry methods were used to characterise proliferative activity, cell cycle progression, and apoptosis of B cells in which JunD was either knocked down or overexpressed. The immune status and autophagic activity of these cells were assessed using Western immunoblotting and enzyme-linked immunosorbent assay (ELISA). Additionally, a JunD knockdown mouse model was established, and the functional role of B cell JunD expression in the pathogenesis of SLE was assessed using Western immunoblotting, ELISA, and haematoxylin and eosin staining. Results: B cells from patients with SLE exhibited upregulation of JunD, with overexpression facilitating in vitro cellular proliferation and modulation of the immune and autophagic status of these B cells. JunD knockdown was also sufficient to modulate in vivo immune function and the autophagic status of B cells. Conclusion: JunD was upregulated in the B cells of patients with SLE, where it regulates proliferation, autophagy, and immunity.

Inhaling polyhexamethylene guanidine (PHMG) aerosol, a broad-spectrum disinfectant, can lead to severe pulmonary fibrosis. Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, is believed to play a role in the chemical-induced pulmonary injury. This study aimed to investigate the mechanism of ferroptosis in the progression of PHMG-induced pulmonary fibrosis. C57BL/6 J mice and the alveolar type II cell line MLE-12 were used to evaluate the toxicity of PHMG in vivo and in vitro, respectively. The findings indicated that iron deposition was observed in PHMG induced pulmonary fibrosis mouse model and ferroptosis related genes have changed after 8 weeks PHMG exposure. Additionally, there were disturbances in the antioxidant system and mitochondrial damage in MLE-12 cells following a 12-hour treatment with PHMG. Furthermore, the study observed an increase in lipid peroxidation and a decrease in GPX4 activity in MLE-12 cells after exposure to PHMG. Moreover, pretreatment with the ferroptosis inhibitors Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) not only restored the antioxidant system and GPX4 activity but also mitigated lipid peroxidation. Current data exhibit the role of ferroptosis pathway in PHMG-induced pulmonary fibrosis and provide a potential target for future treatment.

ObjectiveTo analyze the clinical efficacy of CO2 fractional laser combined with compound betamethasone in treating vitiligo and its impact on inflammatory factors.MethodsThe clinical treatment effects, levels of inflammatory factors [interleukin-17 (IL-17), interferon-gamma (IFN-γ), interleukin-10 (IL-10)], prognosis regarding repigmentation and relapse, psychological health (satisfaction).Results① Clinical treatment effects: the total effective rate in Group A was 92.73%, Group B was 74.55%, and Group C was 67.27%, with Group A showing significantly higher effectiveness than Groups B and C (p 0.05); after 3 and 6 months of treatment, the levels of IL-17 and IFN-γ decreased significantly while IL-10 levels increased significantly across all three groups, with Group A showing a more pronounced change compared to Groups B and C (p 0.05).ConclusionThe application of CO2 fractional laser combined with compound betamethasone in vitiligo patients demonstrates significant efficacy. Compared to sole treatment with CO2 fractional laser or compound betamethasone injections, this combined approach further improves the levels of inflammatory factors in vitiligo patients, reduces the risk of relapse, enhances skin repigmentation, improves quality of life, psychological well-being, without increasing the risk of related adverse reactions. This combined approach merits clinical promotion and application.

Abstract. Background:. Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. Methods:. This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. Results:. At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%-69%) and 45% (low vs. placebo, 95% CI 26%-64%), with both P values

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-β1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

In view of the diversity of gas reservoir classification and the differences of characteristics of geology and development in different gas reservoirs, it is necessary to study the adaptability of gas reservoir classification. This paper analyzes and summarizes the current classification methods of gas reservoirs, studies the microscopic pore characteristics and seepage mechanism of different gas reservoirs. The commonalities and individualities of seepage laws in different gas reservoirs are determined, the key factors that determine the development dynamics and effects of gas reservoirs are proposed, and the gas reservoirs types are divided from the perspective of development. The results show that the development characteristics of gas reservoirs are determined by the seepage law, and the seepage law is determined by the microscopic pore characteristics. Therefore, from the perspective of development, the microscopic pore characteristics are the fundamental of gas reservoir classification. Gas reservoirs can be divided into four types: tight, low permeability, medium and high permeability, and fractured. This classification method can unify the types of gas reservoirs according to the seepage laws of different gas reservoirs, establish corresponding seepage models, evaluate productivity, and predict performance. It is of great significance for rational, efficient and scientific development of gas fields.

Shale gas, as an important unconventional natural gas resource, is the main force to increase natural gas reserves and production in the future. For shale gas with huge resources, it is particularly important to accurately evaluate its development potential and realize scale benefit development. Given the importance of shale gas production evaluation in the context of digital transformation of the oil and gas industry, this paper presents a systematic review and examination of the application of data-driven technology in shale gas production evaluation to provide an overview of their current status. With the deepening of shale gas development theory and the maturity of data-driven technology, the existing data-driven technology has made great progress in shale gas production evaluation. It is worth noting that the application of these technologies in actual production needs to be further refined to assess shale gas production more accurately in various production demand scenarios, thereby effectively guiding production optimization and development plans. Therefore, in view of the limitations of the application of data-driven technology in shale gas production evaluation, this paper puts forward some possible priorities and trends in the future, aiming to optimize the application of data-driven technology in shale gas production evaluation in the future as much as possible.

Accurate diagnostic techniques and effective therapeutic methods are required to treat H. pylori. The application of chicken single-chain variable fragment (scFv) antibodies may diagnose and treat H. pylori. This study used the phage display technique to construct a chicken-derived immune scFv antibody library against H. pylori. Total RNA was extracted from the spleens of five immunized chickens and reverse transcribed into cDNA. A fragment of scFv was produced by overlap extension PCR and cloned into a pHEN2 phagemid vector. After the package with the M13KO7 helper phage, the recombinant HpaA protein was used as a target antigen to validate the screening ability of our antibody library by bio-panning. The dilution counting results showed that the size of the primary antibody library was estimated to be 1 × 109 cfu/mL. PCR analysis of 47 clones from the library revealed that about 100% of the clones were positive with scFv fragments, and there were no identical sequences, indicating the good diversity of the antibody library. After three rounds of bio-panning, high-affinity antibodies against recombinant HpaA protein were successfully obtained. The selected antibody specifically recognized HpaA protein in nine different H. pylori strains, confirming the screening ability of our library. The chicken immune scFv antibody library against H. pylori was successfully constructed, and the antibody library’s screening ability was validated by selecting specific scFv antibodies against recombinant HpaA and clinical strains. It provided a simple and rapid method to obtain antibodies against H. pylori for diagnosis or treatment.

Abstract Introduction To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). Methods Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. Results Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. Conclusions Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

Metal and metal oxide nanoparticles (NPs) embedded in glass matrixes exhibit special optical, electrical, or magnetic properties. Despite various approaches of encapsulating NPs in different kinds of glasses to prepare functional composite materials, there still exist challenges in fabricating efficiency and performance for silica glass made by traditional methods, such as sol–gel or melt quenching. Herein, the authors report a facile way to fabricate metal oxide NP‐doped silica glass by digital light processing (DLP) 3D printing technology for the first time. Different from common ion doping in silica glass, metal acetylacetonates that can be thermally decomposed to corresponding metal oxides innocuously, are chosen as a general precursor. Then, the representative nickel(II) acetylacetonate is introduced during the 3D printing process. The subsequent heat treatment generates a homogeneous distribution of NiO NPs in silica glass and it also exhibits optical nonlinear effect. The results provide a facile method for developing functional metal oxide‐doped glasses as well as the freeform fabrication of optoelectronic devices based on them.

BackgroundBisphenol A (BPA) is an oil-derived, large-market volume chemical with endocrine disrupting properties and reproductive toxicity. Moreover, BPA is frequently used in food contact materials, has been extensively researched recently, and widespread exposure in the general population has been reported worldwide. However, national information on BPA levels in general Chinese people is lacking.MethodsThis study collected and analyzed 145 (104 in urine and 41 in serum) research articles published between 2004 and 2021 to reflect the BPA internal exposure levels in Chinese populations. The Monte Carlo simulation method is employed to analyze and estimate the data in order to rectify the deviation caused by a skewed distribution.ResultsData on BPA concentrations in urine and serum were collected from 2006 to 2019 and 2004 to 2019, respectively. Urinary BPA concentrations did not vary significantly until 2017, with the highest concentration occurring from 2018 to 2019 (2.90 ng/mL). The serum BPA concentration decreased to the nadir of 1.07 ng/mL in 2011 and gradually increased to 2.54 ng/mL. Nationally, 18 provinces were studied, with Guangdong (3.50 ng/mL), Zhejiang (2.57 ng/mL), and Fujian (2.15 ng/mL) having the highest urine BPA levels. Serum BPA was investigated in 15 provinces; Jiangsu (9.14 ng/mL) and Shandong (5.80 ng/mL) were relatively high. The results also indicated that males’ urine and serum BPA levels were higher than females, while the BPA levels in children were also higher than in adults (p

Abstract Background Recurrent wheezing is a common clinical problem in early childhood, which is associated with significant morbidity. There is no international consensus on the management and prevention of recurrent wheezing; therefore, identifying the risk factors associated with recurrent wheezing is crucial to prevent episodes of wheezing in young children. Methods In this retrospective study, we collected the data of 24,737 patients who were admitted to our hospital between 27th April 2012 and 11th September 2019. After screening for patients with wheezing, we identified 8572 patients with a primary diagnosis of pneumonia with wheezing. Patients’ clinical data were collected from the hospital medical records. Patients were stratified for age in the groups of 12 months. Results Among the 8569 pediatric pneumonia patients with wheezing, there were 343 patients with recurrent wheezing. Most enrolled patients were under 6 months of age (45.17%) and had a normal birth weight (86.95%). Winter was the most common onset season for the first episode of wheezing, while spring was the most common season for the second episode of wheezing for those with recurrent wheezing. The univariate and multivariate logistic regression analysis for the risk factor associated with recurrent wheezing showed that male gender, past history of respiratory and cardiovascular diseases, low birth weight, development of severe pneumonia, and PICU admission were significantly associated with recurrent wheezing. Conclusion Male gender, past history of respiratory and cardiovascular diseases, low birth weight, severe pneumonia, and PICU admission are independent risk factors of recurrent wheezing in the pediatric population.

Conventional recovery enhancement techniques are aimed at reducing the abandonment pressure, but there is an upper limit for recovery enhancement due to the energy limitation of reservoirs. Gas injection for energy supplementation has become an effective way to enhance gas recovery by reducing hydrocarbon saturation in gas reservoirs. This review systematically investigates progress in gas injection for enhanced gas recovery in three aspects: experiments, numerical simulations and field examples. It summarizes and analyzes the current research results on gas injection for EGR and explores further prospects for future research. The research results show the following: (1) Based on the differences in the physical properties of CO2, N2 and natural gas, effective cushion gas can be formed in bottom reservoirs after gas injection to achieve the effects of pressurization, energy replenishment and gravity differentiation water resistance. However, further experimental evaluation is needed for the degree of increase in penetration ability. (2) It is more beneficial to inject N2 before CO2 or the mixture of N2 and CO2 in terms of EGR effect and cost. (3) According to numerical simulation studies, water drive and condensate gas reservoirs exhibit significant recovery effects, while CO2-EGR in depleted gas reservoirs is more advantageous for burial and storage; current numerical simulations only focus on mobility mass and saturation changes and lack a mixed-phase percolation model, which leads to insufficient analysis of injection strategies and a lack of distinction among different gas extraction effects. Therefore, a mixed-phase-driven percolation model that can characterize the fluid flow path is worth studying in depth. (4) The De Wijk and Budafa Szinfelleti projects have shown that gas injection into water drive and depleted reservoirs has a large advantage for EGR, as it can enhance recovery by more than 10%. More experiments, simulation studies and demonstration projects are needed to promote the development of gas injection technology for enhanced recovery in the future.

As an important indicator for measuring the effectiveness and level of oil and gas field development, recovery rate has always been a focus in the research of oil and gas fields. Reservoirs of tight sandstone gas formations have significant characteristics of low porosity, high permeability, and high water content, which leads to greater difficulty in their development and makes it challenging to evaluate the recovery rate. Newtonian mechanics, as an important component of the mechanical system, is an innovative application of classical mechanics in the field of seepage mechanics when applied to the two-phase flow of gas and water. Firstly, starting from the perspective of mechanics analysis, we derive a steady-state model for gas–water two-phase infiltration and obtain the productivity equation based on this model. Then, according to the steady-state model, we establish a method to calculate the effective control radius of gas reservoirs under different production conditions and reservoir physical properties. Finally, using Matlab 2018a programming based on the productivity equation, we calculate the gas recovery under different conditions during constant pressure drop production and constant production rate production. The results indicate that the effective control radius of the reservoir decreases with an increase in the economic ultimate daily gas production, increases with an increase in production pressure difference, slightly decreases with an increase in startup pressure gradient, and correspondingly increases with an increase in microtube radius and quantity. Regardless of whether it is production with a fixed pressure drop or production with a fixed production rate, the gas recovery decreases as the production pressure drop and bottomhole abandonment pressure increase, but it increases as the proportion of the single-well control radius increases. In production with a fixed pressure drop, the gas recovery remains consistent across different reservoir quality indices. However, in production with a fixed production rate, the gas recovery initially increases rapidly and then gradually slows down as the reservoir quality index increases, and there is an obvious critical permeability (0.1 mD). The research findings are based on the mechanical analysis of porous media, delving into the laws governing fluid flow during infiltration. The derived infiltration model can be used to calculate the effective control radius and evaluate recovery rates, providing practical guidance for reservoir development.

Abstract Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody‐melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio‐synthetically fabricated, with the recombinant protein (hGC33 scFv‐melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14‐responsive manner at tumor sites, which reduced off‐target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small‐molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co‐delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM‐based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.

An embedded core fiber sensor based on surface plasmon resonance (SPR) principle is developed. In the structure of optical fiber, the middle of the optical fiber cladding is hollowed out. The hollowed-out part is then filled with a temperature-sensitive layer. For the temperature sensitive layer, polydimethylsiloxane(PDMS) is chosen. A metal layer is placed outside the cladding of the optical fiber to detect changes in the external environment and stimulate the SPR effect.The gold metal(Au) layer is also placed between the cladding and the PDMS to stimulate the SPR effect.The refractive index of seawater varies with salinity and temperature through COMSOL Multiphysics finite element simulation. We can measure the two parameters of salinity and temperature at the same time based on the SPR principle. The sensitivity of salinity and temperature calculated by this sensor is 0.193 nm/%, 0.397 nm/°C. Fiber optic sensors use the SPR principle to detect dynamic, real-time, continuous processes. The measurement range is very wide, and the brightness is also very high.Compared with single-channel measurement of single parameter, this sensor can greatly improve the efficiency of two-parameter measurement. The sensor has the advantages of simple structure, low production cost and high sensitivity, which can realize the simultaneous measurement of two parameters and avoid the crosstalk between parameters. It has great research significance.

Arcobacter was recognized as an emerging enteropathogen and controversies regarding its classification persisted. This study aimed to reevaluate the taxonomy of Arcobacter utilizing the 16S rRNA gene, 23S rRNA gene, single-copy orthologous genes, as well as genomic indices such as Average Nucleotide Identity (ANI) and in silico DNA–DNA hybridization (isDDH). The taxonomy of this genus was reevaluated in this study using multiple indices with a dataset of 371 genomes comprising 34 known species and 14 potentially new species. Good discrimination could be achieved only in some species but not for the species with higher sequence similarity using the comparisons of the 16S rRNA gene and 23S rRNA gene sequences. A high-accuracy phylogenomic approach for Arcobacter was established using 84 single-copy orthologous genes obtained through various bioinformatics methods. One marker gene (gene711), which was found to possess the same distinguishing ability as ANI, isDDH, and single-copy orthologous methods, was identified as a reliable locus for inferring the phylogeny of the genus. The effective species classification was achieved by employing gene711 with a sequence similarity exceeding 96%, even for species like A. cloacae, A. lanthieri, and A. skirrowii, which exhibited ambiguous classification using ANI and isDDH. Additionally, excellent subspecies categorizing among A. cryaerophilus could be distinguished using gene711. In conclusion, this framework strategy had the potential advantage of developing rapid species identification, particularly for highly variable species, providing a novel insight into the behavior and characteristics of Arcobacter.

Abstract Background The tumor microenvironment (TME) in breast cancer plays a vital role in occurrence, development, and therapeutic responses. However, immune and stroma constituents in the TME are major obstacles to understanding and treating breast cancer. We evaluated the significance of TME-related genes in breast cancer. Methods Invasive breast cancer (BRCA) samples were retrieved from the TCGA and GEO databases. Stroma and immune scores of samples as well as the proportion of tumor infiltrating immune cells (TICs) were calculated using the ESTIMATE and CIBERSORT algorithms. TME-related differentially expressed genes (DEGs) were analyzed by a protein interaction (PPI) network and univariate Cox regression to determine CD1C as a hub gene. Subsequently, the prognostic value of CD1C, its response to immunotherapy, and its mechanism in the TME were further studied. Results In BRCA, DEGs were determined to identify CD1C as a hub gene. The expression level of CD1C in BRCA patients was verified based on the TCGA database, polymerase chain reaction (PCR) results, and western blot analysis. Immunohistochemical staining (IHC) results revealed a correlation between prognosis, clinical features, and CD1C expression in BRCA. Enrichment analysis of GSEA and GSVA showed that CD1C participates in immune-associated signaling pathways. CIBERSORT showed that CD1C levels were associated with tumor immune infiltrating cells (TILs), such as different kinds of T cells. Gene co-expression analysis showed that CD1C and the majority of immune-associated genes were co-expressed in BRCA. In renal cell carcinoma, patients with a high expression of CD1C had a better immunotherapy effect. Conclusion CD1C is an important part of the TME and participates in immune activity regulation in breast tumors. CD1C is expected to become a prognostic marker and a new treatment target for breast cancer.

Accurate Channel State Information (CSI) is critical for maximizing the throughput of massive Multi-Input Multi-Output (mMIMO) systems. Due to the environment dynamics and user mobility, CSI aging is a major challenge to achieving the large throughput of mMIMO promised by theory. CSI prediction can be used to overcome this without increasing the signaling overhead. Motivated by the anticipated native support for Artificial Intelligence (AI) in the fifth generation and beyond cellular standards, we propose deep learning CSI prediction solutions based on 3-Dimensional (3D) Complex Convolutional Neural Networks (CCNN). These solutions provide improved capabilities for capturing temporal and spatial correlations, enhancing CSI prediction performance. In particular, they utilize the angle delay decomposition of previously observed CSI to predict the future one. In one architecture, the network, dubbed CSI Prediction Network (CSI-PNet), uses small kernels with circular padding to efficiently capture the correlation between propagation paths in the angle domain. This architecture can be further improved by the use of an attention-like model to vary the weights and enhance prediction performance adaptively. We also propose methods to enhance robustness to noise and time and frequency offsets. We tested these solutions using 3GPP-compatible simulations and field measurements in a commercial network. Our solutions demonstrate stable performance and significantly outperform several benchmarks, especially at low and medium speeds. They strike a balance between performance and architecture complexity, indicating suitability for actual implementation.

In this paper, we introduce the concept of an S-asymptotically ω-periodic process in distribution for the first time, and by means of the successive approximation and the Banach contraction mapping principle, respectively, we obtain sufficient conditions for the existence and uniqueness of the S-asymptotically ω-periodic solutions in distribution for a class of stochastic fractional functional differential equations.

The United Nations Secretary-General Mechanism (UNSGM) for investigation of the alleged use of chemical and biological weapons is the only established international mechanism of this type under the UN. The UNGSM may launch an international investigation, relying on a roster of expert consultants, qualified experts, and analytical laboratories nominated by the member states. Under the framework of the UNSGM, we organized an external quality assurance exercise for nominated laboratories, named the Disease X Test, to improve the ability to discover and identify new pathogens that may cause possible epidemics and to determine their animal origin. The “what-if” scenario was to identify the etiological agent responsible for an outbreak that has tested negative for many known pathogens, including viruses and bacteria. Three microbes were added to the samples, Dabie bandavirus, Mammarenavirus, and Gemella spp., of which the last two have not been taxonomically named or published. The animal samples were from Rattus norvegicus, Marmota himalayana, New Zealand white rabbit, and the tick Haemaphysalis longicornis. Of the 11 international laboratories that participated in this activity, six accurately identified pathogen X as a new Mammarenavirus, and five correctly identified the animal origin as R. norvegicus. These results showed that many laboratories under the UNSGM have the capacity and ability to identify a new virus during a possible international investigation of a suspected biological event. The technical details are discussed in this report.

The existing tight oil reservoirs are mainly developed after hydraulic fracturing of horizontal Wells with low recovery. Traditional enhanced oil recovery (EOR) methods are difficult to apply in tight reservoirs, because huff-puff drives oil to the distal end, water breakthrough exists in inter-well flooding, and ASP flooding cannot enter the small pore throat of the tight reservoir. A new EOR method of inter-fracture flooding is proposed. This method solves the problem that the injection water cannot enter the matrix in tight reservoir by inter-fracture flooding. Inter-fracture flooding reduces the distance between the injection and production ends and reduces the risk of water channeling. Inter-fracture flooding increases the pressure gradient during water flooding in the reservoir and establishes an effective water displacement system in the heterogeneous tight reservoir. In this paper, physical simulation experiments and numerical simulation are designed to study the EOR effect of inter-fracture water flooding in heterogeneous tight reservoirs. The results showed the following: (1) Inter-fracture asynchronous water flooding (IFAWF) can improve oil displacement efficiency by 6%–16% compared with inter-fracture synchronous water flooding (IFSWF). (2) Compared with IFSWF, IFAWF can greatly improve the oil displacement efficiency of the core with low permeability in the heterogeneous model by more than 20%. (3) Effective water sweep cannot be achieved by IFSWF, but can be achieved by IFAWF. (4) IFAWF established effective displacement in 0.1mD tight heterogeneous reservoir. Studies have shown that inter-fracture flooding can lower the reservoir development permeability threshold and will be an important EOR method for tight oil and shale oil in the future.

Water production from gas wells is a key factor affecting the effectiveness of gas-reservoir development, and it poses serious challenges in terms of increasing the degree of recovery during the waterless production stage and reducing the impact of water production on gas-reservoir development in the middle and later periods. Thus, gas reservoirs must be efficiently exploited on the basis of identifying gas-water layers accurately, defining gas-water relationships, and understanding gas-water production performance. Accordingly, this study analyzes the production characteristics in gas reservoirs with different gas-water relationships, and it summarizes the rules that determine water-gas ratios. The results reveal that the water-gas ratio increases rapidly in the early stage of water production, but after a period of time, it enters a relatively stable state in which it is almost a fixed value. According to the material balance equation, the theoretically calculated water-gas ratio is fully consistent with the production rules for an entire confined gas reservoir. This shows that the reality of gas-well-water production must be faced, and that the development of water-bearing gas reservoirs must accommodate gas and water co-production. The gas-water relationship, water body scale, and reservoir heterogeneity determine the time of water breakthrough and the water-gas ratio. Therefore, we should change the traditional “water fear” concept in gas-field development, aim for an overall improvement in recovery, face up to the fact that gas wells produce water, and coordinate the development of multi-wells for entire gas reservoirs, all of which will achieve the ultimate goal of improved gas recovery.

Raman distributed optical fiber temperature sensors possess the unique capability of measuring spatial environmental temperatures, which can be of great interest in several fields of application. The key physics barrier to spatial resolution for most optical time-domain reflection (OTDR) systems is the positioning principle of pulse-time-flight. It obtains the spatial resolution of the existing Raman distributed optical fiber temperature sensor, with the kilometer-level sensing distance being limited to the meter-level. Here, we propose a chaotic laser Raman distributed optical fiber temperature sensing scheme that replaces the traditional OTDR positioning principle used for more than 40 years with the chaotic correlation positioning principle. The proposed scheme possesses the characteristics of the chaos Raman scattering light excited by the chaos signal along the sensing fiber. A novel measurement mechanism based on chaotic time-domain differential reconstruction and chaotic correlation demodulation is developed, and a relationship between the temperature variation information and the chaotic correlation peak is experimentally demonstrated. Importantly, the proposed optics mechanism scheme overcomes the physics limitation of the effect of a wide pulse width on sensing spatial resolution; its spatial resolution is optimized from 50 to 0.3 m under the modulation of a 500 ns pulse width. This scheme provides a new concept for chaos optics and fiber sensing research.

Abstract Highly pathogenic coronavirus (CoV) infection induces a defective innate antiviral immune response coupled with the dysregulated release of proinflammatory cytokines and finally results in acute respiratory distress syndrome (ARDS). A timely and appropriate triggering of innate antiviral response is crucial to inhibit viral replication and prevent ARDS. However, current medical countermeasures can rarely meet this urgent demand. Here, an antiviral nanobiologic named CoVR‐MV is developed, which is polymerized of CoVs receptors based on a biomimetic membrane vesicle system. The designed CoVR‐MV interferes with the viral infection by absorbing the viruses with maximized viral spike target interface, and mediates the clearance of the virus through its inherent interaction with macrophages. Furthermore, CoVR‐MV coupled with the virus promotes a swift production and signaling of endogenous type I interferon via deregulating 7‐dehydrocholesterol reductase (DHCR7) inhibition of interferon regulatory factor 3 (IRF3) activation in macrophages. These sequential processes re‐modulate the innate immune responses to the virus, trigger spontaneous innate antiviral defenses, and rescue infected Syrian hamsters from ARDS caused by SARS‐CoV‐2 and all tested variants.

The current increase in resistance to antifungal drugs indicates that there is an urgent need to explore novel antifungal drugs with different mechanisms of action. Phosundoxin is a biphenyl aliphatic amide using a TPP-targeting strategy which targets mitochondria. To provide insights into the antifungal activities of phosundoxin, the antifungal susceptibility testing of phosundoxin was conducted on 158 pathogenic fungi and compared to that of traditional azole drugs. Phosundoxin displayed a broad-spectrum antifungal activity on all the tested yeast-like and filamentous fungi ranging from 2 to 16 mg/L. In particular, azole-resistant clinical isolates of Candida albicans were susceptible to phosundoxin with the same MICs as azole-susceptible C. albicans. Transcriptome analysis on azole-resistant C. albicans identified 554 DEGs after treatment with phosundoxin. By integrating GO and KEGG pathway enrichment analysis, the antifungal activity of phosundoxin was related to impairment of mitochondrial respiratory chain function. Acute oral and percutaneous toxicity of phosundoxin to rats showed that the compound phosundoxin were mild toxicity and LD50 was above 5000 mg/kg body weight in rats. This study demonstrated the potential of phosundoxin as an antifungal agent for the treatment of common fungal infection and contributed to providing insights into the mechanisms of action of phosundoxin against C. albicans.

Objective To further clarify the role of TAMs autophagy in regulating the EMT and migration and invasion of A375 cells, the effects of TAMs autophagy changes on the biological behaviors of A375 cells co-cultured with TAMs were studied. Methods Human monocyte THP-1 cells were induced into M2 type by PMA and IL-4 for 72 h. The expressions of CD68, CD204 and CD206 on M2 surface were determined by flow cytometry and immunofluorescence, and the polarization efficiency of TAMs was determined. TAMs was treated with rapamycin, an autophagy modulator, for 24 h, and the expressions of LC3-Ⅱ and Beclin-1 were detected by Western blot and immunofluorescence after the removal of autophagy modulator intervention for 48 h. The autophagy level of TAMs after drug intervention was determined. Non-contact co-culture was conducted between TAMs after rapamycin intervention and human melanoma A375 cells. Routine culture in the above incubator was conducted by adding low concentration TanⅡA group (1 mg/L) and high concentration TanⅡA group (4 mg/L). After 48 hours of culture, Western blot was used to detect the expression of EMT-related factors in A375 cells, and transwell was used to detect the invasion and migration of A375 cells. Results Human monocyte (THP-1) was treated with PMA and IL-4 for 72 h. Flow cytometry and immunofluorescence detection showed that the expressions of CD68, CD204 and CD206 on M2 surface were significantly increased compared with M0 group, and the difference was statistically significant (all P

Objective To investigate the effect of Beclin1 overexpression on autophagy and EMT in melanoma A375 cells. Methods Human malignant melanoma A375 cells were divided into three groups by liposome transfection, i.e., blank group(no plasmid), NC group(transfection empty plasmid), and transfection group(transfection with Beclin1). These three groups were inoculated subcutaneously in three groups of nude mice for 21 days after tumor formation. The expression levels of mRNA and proteins, including Beclin1, LC3Ⅱ, Vimentin, N-cadherin and E-cadheirn, were detected by RT-PCR and Western blotting, respectively. Results Although tumor developed in all three groups, the tumor growth rate was significantly lower in the transfection group than in either blank or NC groups (P0.05). Compared with the blank and NC groups, the transfection group displayed significantly higher expression levels of both mRNA and proteins for Beclin1, LC3Ⅱ and E-cadherin (P