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Abstract Myosin VI is the only molecular motor that moves towards the minus end along actin filaments. Numerous cellular processes require myosin VI and tight regulations of the motor’s activity. Defects in myosin VI activity are known to cause genetic diseases such as deafness and cardiomyopathy. However, the molecular mechanisms underlying the activity regulation of myosin VI remain elusive. Here, we determined the high-resolution cryo-electron microscopic structure of myosin VI in its autoinhibited state. Our structure reveals that autoinhibited myosin VI adopts a compact, monomeric conformation via extensive interactions between the head and tail domains, orchestrated by an elongated single-α-helix region resembling a “spine”. This autoinhibited structure effectively blocks cargo binding sites and represses the motor’s ATPase activity. Certain cargo adaptors such as GIPC can release multiple inhibitory interactions and promote motor activity, pointing to a cargo-mediated activation of the processive motor. Moreover, our structural findings allow rationalization of disease-associated mutations in myosin VI. Beyond the activity regulation mechanisms of myosin VI, our study also sheds lights on how activities of other myosin motors such as myosin VII and X might be regulated.

BackgroundResearch findings indicate a putative indirect or latent association between phenylalanine (Phe) and Parkinson’s disease (PD). In this study, we aimed to analyze the causal relationship between Phe and PD by two sample Mendelian randomization (MR) analysis.MethodsIn this study, the PD-related dataset and Phe-related dataset were downloaded from Integrative Epidemiology U1nit (IEU) Open Genome-Wide Association Study (GWAS) database. Four algorithms (MR Egger, maximum likelihood, inverse variance weighting (IVW) and unweighted regression) were used to perform MR analysis. The sensitivity analysis (heterogeneity test, horizontal pleiotropy test and Leave-One-Out (LOO) analysis) was used to assess the reliability of MR analyses.ResultsIn the forward MR analysis, Phe was a safety factor for PD (p-value < 0.05 and odds ratios (OR) < 1). The results of reverse MR analysis showed that there was no causal relationship between PD and Phe (p-value > 0.05). In addition, sensitivity analysis showed that MR analysis was reliable.ConclusionThe results of this study revealed that Phe was a safety factor for PD, meaning that Phe reduced the risk of PD.

Summary: Although more and more evidence has supported that metabolic syndrome (MS) is linked to ischemic stroke (IS), the molecular mechanism and genetic association between them has not been investigated. Here, we combined the existing single-cell RNA sequencing (scRNA-seq) data and mendelian randomization (MR) for stroke to understand the role of dysregulated metabolism in stroke. The shared hub genes were identified with machine learning and WGCNA. A total of six upregulated DEGs and five downregulated genes were selected for subsequent analyses. Nine genes were finally identified with random forest, Lasso regression, and XGBoost method as a potential diagnostic model. scRNA-seq also show the abnormal glycolysis level in most cell clusters in stroke and associated with the expression level of hub genes. The genetic relationship between IS and MS was verified with MR analysis. Our study reveals the common molecular profile and genetic association between ischemic stroke and metabolic syndrome.

Introduction: Nearly vertical coal seams present a significant challenge for the coal mining industry due to their difficult accessibility. However, these seams account for a substantial proportion of the world’s coal reserves. Therefore, it is vital to conduct research on disaster control techniques for safe mining of these seams.Method: The research team used experimental research, theoretical analysis, and numerical calculation methods to investigate the creep characteristics and failure mechanisms of layered sandstone roadway in nearly vertical coal seam.Results and discussion: These findings revealed that the maximum moment and concentrated stress of the sandstone located on the side of the roadway roof was positioned in the middle of the nearly vertical structure, making it more susceptible to transverse shear failure. On the other hand, the nearly vertical structure on the floor side was prone to shear slip failure initiated from the bottom of the structure. This led to the asymmetric instability of the roadway. The practical implications of this research are significant for the safe mining of nearly vertical coal seams. The results could help inform the development of disaster control techniques.

BackgroundFor children who are unable to cooperate due to severe dental anxiety (DA), dental treatment of childhood caries under Dental General Anesthesia (DGA) is a safe and high-quality treatment method. This study aims to evaluate the impact on neurocognitive functions and the growth and development of children 2 years after dental procedure based on previous research, and further establish a causal relationship between general anesthesia (GA) and changes in children’s neurocognitive functions by incorporating Mendelian Randomization (MR) analysis.MethodsData were collected and analyzed from 340 cases of S-ECC procedures of preschool children conducted in 2019. This involved comparing the neurocognitive outcomes 2 years post-operation of preschool children receiving dental procedures under general anesthesia or local anesthesia. Physical development indicators such as height, weight, and body mass index (BMI) of children were also compared at baseline, half a year post-operation, and 2 years post-operation. We performed a Mendelian randomization analysis on the causal relationship between children’s cognitive development and general anesthesia, drawing on a large-scale meta-analysis of GWAS for anesthesia, including multiple general anesthesia datasets.ResultsOutcome data were obtained for 111 children in the general anesthesia group and 121 children in the local anesthesia group. The mean FSIQ score for the general anesthesia group was 106.77 (SD 6.96), while the mean score for the local anesthesia group was 106.36 (SD 5.88). FSIQ scores were equivalent between the two groups. The incidence of malnutrition in children in the general anesthesia group was 27.93% (p 0.05) after 2 years, which was not different from the general population. The IVW method suggested that the causal estimate (p = 0.99 > 0.05, OR = 1.04, 95% CI = 5.98 × 10−4–1.82 × 103) was not statistically significant for disease prevalence. This indicates no genetic cause-and-effect relationship between anesthesia and childhood intelligence.ConclusionThere were no adverse outcomes in neurocognitive development in 2 years after severe early childhood caries (S-ECC) procedure under total sevoflurane-inhalation in preschool children. The malnutrition condition in children can be improved after S-ECC procedure under general anesthesia. Limited MR evidence does not support a correlation between genetic susceptibility to anesthesia and an increased risk for intelligence in children.

Background: Chronic subdural hematoma (CSDH) is a prevalent form of intracranial haemorrhage encountered in neurosurgical practice, and its incidence has notably risen in recent years. Currently, there is a lack of studies that have comprehensively classified the cells present in hematomas removed during surgery, and their correlation with CSDH recurrence remains elusive. This study aims to analyse the subcellular populations and occupancy levels within peripheral blood. Methods: This study analyses the subcellular populations and occupancy levels within peripheral blood and postoperatively removed hematomas by single-cell sequencing and attempts to analyse the effect of different cell occupancies within peripheral blood and intraoperatively removed hematomas on CSDH. Results: The single-cell sequencing results showed that the cells were classified into 25 clusters by differential gene and UMAP dimensionality reduction clustering analyses and further classified into 17 significant cell populations by cell markers: pDCs, CD8 T cells, CD4 T cells, MigDCs, cDC2s, cDC1s, plasma cells, neutrophils, naive B cells, NK cells, memory B cells, M2 macrophages, CD8 Teffs, CD8 MAIT cells, CD4 Tregs, CD19 B cells, and monocytes. Further research showed that the presence of more cDC2 and M2 macrophages recruited at the focal site in patients with CSDH and the upregulation of the level of T-cell occupancy may be a red flag for further brain damage. ROS, a marker of oxidative stress, was significantly upregulated in cDC2 cells and may mediate the functioning of transcription proteins of inflammatory factors, such as NFκB, which induced T cells' activation. Moreover, cDC2 may regulate M2 macrophage immune infiltration and anti-inflammatory activity by secreting IL1β and binding to M2 macrophage IL1R protein. Conclusion: The detailed classification of cells in the peripheral blood and hematoma site of CSDH patients helps us to understand the mechanism of CSDH generation and the reduction in the probability of recurrence by regulating the ratio of cell subpopulations.

Introduction Accumulating studies have shown that copper has a detrimental effect in cells, and the cuproptosis-related gene signatures have been constructed as clinical tools to predict prognosis in tumors. However, the heterogeneity of cuproptosis has not been fully investigated in ischemic stroke. Material and methods Here, we combined the bulk RNA-seq and single cell-RNA-seq data for stroke to investigate the role of cuproptosis in stroke. Results We identified the cuproptosis-related differentially expressed genes (CuDEGs) in ischemic stroke. Then, we tried to find the hub genes with the machine learning method and WGCNA. We highlighted four genes identified by these methods and proposed a potential diagnostic model in ischemic stroke. Conclusions Our findings revealed cuproptosis-related hub genes, which could provide useful biomarkers in ischemic stroke.

ABSTRACTThe LMNA gene encoding lamin A/C is amplified in some clear cell renal cell carcinoma (ccRCC) samples. Our data showed that depletion of the tumor suppressor PBRM1 can upregulate lamin A/C levels, and lamin A/C could interact with PBRM1. However, the role of lamin A/C in ccRCC is not yet fully understood. Our functional assays showed that although the proliferation ability was slightly impaired after LMNA depletion, the migration and invasion of ccRCC cells were significantly inhibited. This suppression was accompanied by a reduction in MMP2, MMP9, AKT/p-AKT, and Wnt/β-catenin protein levels. Our data therefore suggest that lamin A/C, as an interaction partner of the tumor suppressor PBRM1, plays a crucial role in tumor invasion and metastasis in ccRCC.

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.

Statement of problem: Bibliometric analysis methods were used to evaluate pediatric dental sedation research and to identify topical hotspots using quantitative and qualitative methodologies. Purpose: To conduct bibliometric analysis on the retrieved data and to foresee the development of trends and hotspots in this research area. Material and methods: We retrieved appropriate research articles from the Web of Science Core Collection on January 1, 2023. VOSviewer, Citespace and the Bibliometrics website were used to conduct bibliometric analysis on the retrieved data. GraphPad Prism 10.0 (GraphPad, San Diego, CA, USA) was used to conduct the statistical analysis. Results: A total of 396 publications on pediatric sedation in dentistry, published between 1993 and 2022, were retrieved from online databases. The USA published most papers. Furthermore, the most frequent countries who cooperated were the USA and Canada. Six of the top ten publishing establishments were USA based. Papers on the research have appeared primarily in the journals of Dentistry and Anesthesiology. Keyword co-occurrence and co-citation cluster analysis revealed that the most common topics mainly were: dental anxiety; conscious sedation; dental caries; midazolam; propofol; hypoxemia. Conclusions: During the three decades, the focus of pediatric sedation research has been on drugs, dental anxiety and procedural sedation. Keyword burst detection indicated that procedural sedation; adverse event; respiratory depression is an emerging research hotspot.

Introduction To investigate shared gene signatures between COVID-19 and ischemic stroke. Material and methods Combining the existing bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) data for COVID-19 to obtain a more comprehensive understanding of the role of dysregulated metabolism. Results A total of 19 up-regulated differentially expressed genes (DEGs) and 24 down-regulated genes were selected for subsequent analyses. Nine genes were finally identified with the machine learning method as a potential diagnostic model in both ischemic stroke and COVID-19. In addition, the hub genes were related to both immune infiltration and metabolic pathways. Conclusions Our study revealed the common molecular profile of COVID-19 and ischemic stroke.

Abstract Background In recent years, N6-methyladenosine (m6A) methylation modification of mRNA has been studied extensively. It has been reported that m6A determines mRNA fate and participates in many cellular functions and reactions, including oxidative stress. The PLOD2 gene encodes a protein that plays a key role in tissue remodeling and fibrotic processes. Methods The m6A methylation and expression levels of PLOD2 were determined by m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) and MeRIP-quantitative polymerase chain reaction (qPCR) in the testes of varicocele rats compared with control. To determine whether IGF2BP2 had a targeted effect on the PLOD2 mRNA, RNA immunoprecipitation-qPCR (RIP-qPCR) and luciferase assays were performed. CRISPR/dCas13b-ALKBH5 could downregulate m6A methylation level of PLOD2, which plays an important role in PLOD2-mediated cell proliferation and apoptosis in GC-2 cells. Results PLOD2 was frequently exhibited with high m6A methylation and expression level in the testes of varicocele rats compared with control. In addition, we found that IGF2BP2 binds to the m6A-modified 3′ untranslated region (3′-UTR) of PLOD2 mRNA, thereby positively regulating its mRNA stability. Targeted specific demethylation of PLOD2 m6A by CRISPR/dCas13b-ALKBH5 system can significantly decrease the m6A and expression level of PLOD2. Furthermore, demethylation of PLOD2 mRNA dramatically promote GC-2 cell proliferation and inhibit cell apoptosis under oxidative stress. Conclusion As a result, we found that varicocele-induced oxidative stress promoted PLOD2 expression level via m6A methylation modification. In addition, targeting m6A demethylation of PLOD2 by CRISPR/dCas13b-ALKBH5 system can regulate GC-2 cell proliferation and apoptosis under oxidative stress. Taken together, our study has acquired a better understanding of the mechanisms underlying male infertility associated with oxidative stress, as well as a novel therapeutic target for male infertility. Graphical Abstract

For the variable speed variable displacement power unit (VSVDPU), achieving power matching between the permanent magnet synchronous motor (PMSM) and the variable displacement plunger pump (VDPP) is the key to reducing system energy consumption. The control method of adjusting the speed of the PMSM and the displacement of the VDPP is the mainstay of current research and application of the VSVDPU. However, the dynamic properties of the PMSM and VDPP have not been balanced, which affects the control effect of the VSVDPU. This paper proposes a control method of variable speed and variable displacement with low energy consumption and high dynamics. The main idea is based on the efficiency model and dynamic response model of the PMSM and VDPP, and the factors that affect the efficiency and dynamic characteristics of the VSVDPU are analyzed. Guided by the multi-objective optimization algorithm, the optimal combination of speed and displacement under specific working conditions is derived. Simulation and experiment results show that the proposed control method is feasible to improve the efficiency and dynamic characteristics of the VSVDPU.

Polymers of intrinsic microporosity (PIMs) stand out as promising membrane materials with exceptional separation performance. In this study, we crafted a highly efficient gas separation membrane using an emerging material, called cyclohexyl-fused spirobiindane-based PIM (CCS-PIM). The CCS-PIM features a robust and rigid microporous structure with a high specific surface area (SBET ​= ​704.6 ​m2/g), exhibiting excellent CO2-selective adsorption capacity. The CO2 adsorption uptake is 0.78 ​mmol/g at 273 ​K and 0.15 ​bar, leading to IAST selectivity of 25.2 for CO2/N2 (15/85 v/v) and 16.7 for CO2/CH4 (50/50 v/v) at 298 ​K. The precisely tuned pore size of the CCS-PIM membrane leads to an enhanced molecular sieving effect, showcasing superior selectivity across various gas pair separations. It demonstrates an O2/N2 selectivity of 6.03 and a CO2/CH4 selectivity of 26.1, surpassing the 2008 Robeson upper bounds. This study suggests a strategic method to improve gas separation efficiency by customizing a locked PIM structure with precise molecular sieving through the insertion of variously sized rings.

ObjectivesThis study aimed to identify, analyze, and summarize the clinical efficacy of virtual reality (VR) distraction therapy for oral treatment in different hospital settings in contrast to medical interventions that induce anxiety and pain. Furthermore, this review aimed to determine the implications for research and clinical practice of VR distraction therapy.DataThis review investigated the clinical efficacy of VR in the oral treatment of procedural pain or anxiety. Quality assessment of the included studies was conducted. A narrative synthesis of the collected data was performed.SourcesLiterature studies from six electronic databases were searched for a comprehensive review, namely, the Cochrane Oral Health’s Trials Register, Cochrane Central Register of Controlled Trials (Central), MEDLINE (PubMed), EMBASE, Scopus, and Web of Science.Study selectionOne thousand five hundred twenty-two patients aged between 0 and 60 years who used VR during dental treatment were included in this review. Among these studies, 8 and 14 studies comprised adult and pediatric patients.ConclusionOverall, the reviewed studies underscore the efficacy of VR to mitigate pain and anxiety in the context of dental treatment. VR is an innovative pain and anxiety management approach that facilitates dental treatment patients to immerse themselves in a virtual world while using distractions to reduce pain and anxiety.Clinical significanceVR is an effective and novel non-pharmacological method of behavioral management that contributes to improving medication safety for dental patients. VR as a distractive approach can reduce the fear associated with medical interventions and prevent severe pain sensitivity, anxiety, and medical avoidance among adults and children.

Summary: Focal adhesions (FAs) are dynamic protein assemblies that connect cytoskeletons to the extracellular matrix and are crucial for cell adhesion and migration. KANKs are scaffold proteins that encircle FAs and act as key regulators of FA dynamics, but the molecular mechanism underlying their specified localization and functions remains poorly understood. Here, we determine the KANK1 structures in complex with talin and liprin-β, respectively. These structures, combined with our biochemical and cellular analyses, demonstrate how KANK1 scaffolds the FA core and associated proteins to modulate the FA shape in response to mechanical force. Additionally, we find that KANK1 undergoes liquid-liquid phase separation (LLPS), which is important for its localization at the FA edge and cytoskeleton connections to FAs. Our findings not only indicate the molecular basis of KANKs in bridging the core and periphery of FAs but also provide insights into the LLPS-mediated dynamic regulation of FA morphology.

Abstract We aimed to analyse postoperative cognitive dysfunction (POCD) incidence and risk factors in elderly adults who underwent surgery for oral malignancies. A total of 112 elderly patients (aged ≥ 55 years) were selected for expanded resection of oral malignancy and cervical lymphatic dissection at our institution from December 2020 to December 2021. Participants were cognitively evaluated using the neuropsychological test scale 1 day before and 7 days after surgery to determine whether they had developed POCD. Based on whether POCD occurred 7 days after surgery, patients were classified into the POCD and non-POCD groups. Logistic regression was applied to perioperative factors to analyse the risk factors for POCD onset. Seven days after surgery for oral malignancy, there were 37 (33.1%) POCD morbidities. Multiple factor logistic regression analysis revealed that venerable age (odds ratio [OR] = 1.269, 95% confidence interval [CI] 1.056–1.525, P

Abstract Background There are few reported studies on stigma in young and middle-aged stroke patients during the rehabilitation period, however, the rehabilitation period plays a key role in the patients’ disease regression. Exploring the level of stigma and the influencing factors in young and middle-aged stroke patients during the rehabilitation period is crucial for determining how to reduce the level of stigma and improve the patients’ motivation for rehabilitation treatment. Therefore, this study investigated the level of stigma in young and middle-aged stroke patients and analyzed the factors influencing stigma in order to provide a reference or basis for healthcare professionals to develop effective and targeted stigma intervention programs. Methods Using a convenience sampling method, 285 young and middle-aged stroke patients admitted to the rehabilitation medicine department of a tertiary care hospital in Shenzhen, China, from November 2021 to September 2022 were selected and surveyed using a general information questionnaire, the Stroke Stigma Scale(SSS), the Barthel Index(BI), and the Positive and Negative Emotions Scale(PANAS), and multiple linear regression and smoothed curve fitting were used to analyze the factors influencing the stigma of young and middle-aged stroke patients during the rehabilitation period. Results SSS score of 45.08 ± 11.06, univariate analysis of age, occupation, education level, pre-stroke monthly income, insurance type, comorbid chronic disease status, primary caregiver, BI, positive and negative emotion as factors influencing stigma. Multiple linear regression showed that age, pre-stroke monthly income, BI, positive and negative emotions were independent influences on stigma in young and middle-aged stroke patients, explaining 58.0% of the total variance in stigma. A smoothed curve fit revealed a curvilinear relationship between the above influences and stigma. Conclusion Young and middle-aged stroke patients have a moderate level of stigma. Medical staff should focus on young patients aged 18–44 years, those with high monthly income before the stroke, those with poor self-care ability, and those with low positive and high negative emotion scores, and conduct early assessments and adopt targeted intervention programs according to the influencing factors to reduce the stigma of young and middle-aged stroke patients, improve their motivation for rehabilitation, and help them return to their families and society as soon as possible. Trial Registration Registration number of China Clinical Trials Registration Center: 20,220,328,004-FS01.

Carbon dioxide storage and utilization has become an inevitable trend and choice for sustainable development under the background of global climate change and carbon neutrality. Carbon industry which is dominated by CO2 capture, utilization and storage/ CO2 capture and storage (CCUS/CCS) is becoming a new strategic industry under the goal of carbon neutrality. The sustainable development of carbon industry needs to learn from the experiences of global oil and gas industry development. There are three types of “carbon” in the earth system. Black carbon is the CO2 that has not been sequestered or used and remains in the atmosphere for a long time; grey carbon is the CO2 that has been fixed or permanently sequestered in the geological body, and blue carbon is the CO2 that could be converted into products for human use through biological, physical, chemical and other ways. The carbon industry system covers carbon generation, carbon capture, carbon transportation, carbon utilization, carbon sequestration, carbon products, carbon finance, and other businesses. It is a revolutionary industrial field to completely eliminate “black carbon”. The development of carbon industry technical system takes carbon emission reduction, zero carbon, negative carbon and carbon economy as the connotation, and the construction of a low-cost and energy-efficient carbon industry system based on CCUS/CCS are strategic measures to achieve the goal of carbon neutrality and clean energy utilization globally. This will promote the “four 80%s” transformation of China's energy supply, namely, to 2060, the percentage of zero-carbon new energy in the energy consumption will be over 80% and the CO2 emission will be decreased by 80% to ensure the carbon emission reduction of total 80×108 t from the percentage of carbon-based fossil energy in the energy consumption of over 80%, and the percentage of CO2 emission from energy of over 80% in 2021. The carbon industry in China is facing three challenges, large CO2 emissions, high percentage of coal in energy consumption, and poor innovative system. Three strategic measures are proposed accordingly, including: (1) unswervingly develop carbon industrial system and ensure the achievement of carbon neutrality as scheduled by 2060; (2) vigorously develop new energy sources and promote a revolutionary transformation of China's energy production and consumption structure; (3) accelerate the establishment of scientific and technological innovation system of the whole CO2 industry. It is of great significance for continuously optimization of ecological environment and construction of green earth and ecological earth to develop the carbon industry system, utilize clean energy, and achieve the strategic goal of global carbon neutrality.

An assessment of animal roadkill can help develop road mitigation measures. This article is the first to report data on animal-vehicle collisions (AVCs) in Nanjing, a supercity in eastern China. The research was conducted on a 224.27 km stretch of nine roads in Nanjing. In the period, between November 2020 and October 2021, 26 fortnightly monitoring missions were conducted to gather roadkill carcasses so that we could analyze their temporal and spatial distribution patterns. A total of 259 carcasses were collected, comprising 22 different species, of which 46.42% were mammals and 48.81% were birds. Cats and dogs are the most roadkill mammals, and blackbirds and sparrows are the most roadkill birds. The temporal analysis demonstrated that the peak of vertebrate roadkill occurred from May to July. Spatial analysis showed that the distribution patterns of vertebrate roadkill on different roads varied with a generally non-random distribution and aggregation. By mapping accidents using kernel density analysis, we were able to pinpoint locations that were at high risk for roadkill. Due to the fortnightly survey, our results would underestimate the casualties, even if, our study suggests that the problem of car accidents due to animals should be a cause for concern, and the results of the analysis of temporal and spatial patterns contribute to the establishment of mitigation measures.

Abstract Apoptosis is one of the major forms of programmed cell death, and it serves vital biological functions in multicellular animal and plant cells. The core mechanism of apoptosis is highly conserved in metazoans, where the translocation of CED-4/Apaf-1 from mitochondria to the nuclear membrane is required to initiate and execute apoptosis. However, the underlying molecular mechanisms of this translocation are poorly understood. In this study, we showed that SAO-1 binds DLC-1 and prevents its degradation to promote apoptosis in C. elegans germ cells. We demonstrated that SAO-1 and DLC-1 regulate CED-4/Apaf-1 nuclear membrane accumulation during apoptosis. Isothermal titration calorimetry-based assay and high-resolution crystal structure analysis further revealed that SAO-1 interacted with DLC-1 to form a 2:4 complex: each of the two β-sheets in the SAO-1 peptide interacted with two DLC-1 dimers. Point mutations at the SAO-1-DLC-1 binding interface significantly inhibited apoptotic corpse formation and CED-4 nuclear membrane accumulation within C. elegans germ cells. In conclusion, our study provides a new perspective on the regulation of CED-4-mediated apoptosis.

A planet’s mass loss is important for the its formation and evolution. The radius valley (RV) is believed to be triggered by evaporation-induced mass loss. As an alternative mechanism for RV, the mass loss of post-impact planets is thoroughly investigated in this work. The impact energy is converted to the planet’s internal energy, enhancing its core energy and accelerating mass loss and orbital migration. As the host star changes from K type to F type, the planet’s mass loss and orbital migration increase. When the initial gas-to-core-mass ratio is small, the migration efficiency for planets around K-type stars will increase, which helps to suppress mass loss and retain the planet’s mass and radius within a specific range. On the contrary, planets around more massive F-type stars experience more substantial mass loss, potentially leading to complete mass loss, and migrate to orbits with longer periods. Our calculation shows that planets around different spectral types of host stars give rise to an RV ranging from 1.3 to 2.0 R _⊕ , consistent with the observed range of 1.3–2.6 R _⊕ . Despite the presence of uncertain parameters, the planetesimal impact can promote the RV establishment for planets around host stars of different spectral types.

Many hot Jupiters may experience orbital decays, which are manifested as long-term transit-timing variations. We have analyzed 7068 transits from the Transiting Exoplanet Survey Satellite (TESS) for a sample of 326 hot Jupiters. These new mid-transit-time data allow us to update ephemerides for these systems. By combining the new TESS transit-timing data with archival data, we searched for possible long-term variations in the orbital period in these hot Jupiters using a linear and a quadratic ephemeris model. We identified 26 candidates that exhibit possible long-term variations of the orbital period, including 18 candidates with decreasing orbital periods and eight candidates with increasing orbital periods. Among them, 12 candidates failed our leave-one-out cross validation test and thus should be considered to be marginal candidates. In addition to tidal interaction, alternative mechanisms such as apsidal precession, the Rømer effect, and the Applegate effect could also contribute to the variations during the observed period. The ephemerides derived in this work are useful for scheduling follow-up observations for these hot Jupiters in the future. The Python code ( PdotQuest , https://github.com/AeoN400/PdotQuest ) used to generate the ephemerides is made available online.

Heartbeat star systems have been reported to exhibit two distinct different orbital dynamic evolution processes: apsidal precession (e.g., KIC 4544587) and orbital decay (e.g., KIC 3766353). While experiencing similar dynamic tidal interactions, these binary systems display different dynamical behaviors, which is a puzzling phenomenon. In this work, we deduced a theoretical relation between the timescale of stellar pulsation Ppul and orbital periods Porb of heartbeat stars based on the resonance criteria representing the orbital local low-energy configuration. The theoretical relation shows that when the ratio of Porb to Ppul is an integer, the specific orbital period is captured in the resonance state, resulting in resonance locking. The resonance criteria are verified by periodograms of the pulsations and orbits of the two systems KIC 4544587 and KIC 3766353 from observations. KIC 4544587 is an apsidal precession heartbeat star with eight observed resonant frequencies available from observations and has an almost integer ratio of Ppul/Porb=67.968. On the contrary, KIC 3766353 is undergoing the process of orbital shrinkage with only three weak pulsation–orbital resonance frequencies available and shows a non-integer ratio of Ppul/Porb=83.163. Given the results, the theoretical relation is a potential proxy to distinguish between apsidal precession and orbital decay binary systems. Furthermore, we predict that the orbital period of KIC 3766353 will be reduced to 2.492 days, at which time it will be transformed into apsidal precession.

AbstractThe life cycles of potamodromous fishes are generally interrupted by the presence of a dam, and populations often display different life history traits between upstream and downstream. This study compared the age and growth rates of grass carp and silver carp above and below Changzhou Dam in the Pearl River. Standard length (SL) composition and back-calculated SL at ages one and two years were greater for grass carp upstream than for downstream individuals; and the length–weight relationship differed between upstream and downstream populations, while the sex ratio, age structure and growth were not significantly different. For silver carp, only SL compositions differed between upstream and downstream populations; sex ratio, age structure, SL-at-age and growth rates were similar. Mean SL-at-age and growth rates of both species were lower at high latitudes than at middle and low latitudes, and populations in the Yangtze River had greater mean SL-at-ages and faster growth relative to silver carp at low latitudes. There were no differences in mean SL or growth among populations at middle and low latitudes. For grass carp, age and growth varied with small-scale ecological processes and regions or latitude, while for silver carp, such variations were proportionate to latitude and the large-scale geographical range. This study provides not only guidelines for fisheries management and conservation of exploited potamodromous fishes, but also insights into the relationship between life history trait variation and adaptive capacity.

Background: Numerous studies have highlighted the crucial role of G protein-coupled receptors (GPCRs) in tumor microenvironment (TME) remodeling and their correlation with tumor progression. However, the association between GPCRs and the TME in glioblastoma (GBM) remains largely unexplored.Methods: In this study, we investigated the expression profile of GPCRs in GBM using integrated data from single-cell RNA sequencing and bulk sequencing. Surgical samples obtained from meningioma and GBM patients underwent single-cell RNA sequencing to examine GPCR levels and cell-cell interactions. Tumor microenvironment (TME) score is calculated by the infiltrated immune cells with CIBERSORT.Results: Our findings revealed a predominantly increased expression of GPCRs in GBM, and demonstrated that the classification of GPCRs and TME is an independent risk factor in GBM. Patients with high GPCR expression in the tumor tissue and low TME score exhibited the worst outcomes, suggesting a potentially aggressive tumor phenotype. On the other hand, patients with low GPCR expression in the tumor tissue and high TME score showed significantly better outcomes, indicating a potentially more favorable tumor microenvironment. Furthermore, the study found that T cells with high GPCR levels displayed extensive cell-cell connections with other tumor and immune cells in the single cell RNA analysis, indicating their potential involvement in immune escape.Conclusion: In conclusion, GPCRs in combination with TME classification can serve as prognostic markers for GBM. GPCRs play an essential role in tumor progression and the TME in GBM.

Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy. Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months. Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were “satisfied” or “very satisfied” with the 10-kHz SCS treatment. Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy. Trial registration: clincaltrials.gov Identifier: NCT03228420

Abstract Subsecond time perception has been frequently attributed to modality-specific timing mechanisms that would predict no cross-modal transfer of temporal perceptual learning. In fact, perceptual learning of temporal interval discrimination (TID) reportedly shows either no cross-modal transfer, or asymmetric transfer from audition to vision, but not vice versa. However, here we demonstrate complete cross-modal transfer of auditory and visual TID learning using a double training paradigm. Specifically, visual TID learning transfers to and optimizes auditory TID when the participants also receive exposure to the auditory temporal interval by practicing a functionally orthogonal near-threshold tone frequency discrimination task at the same trained interval. Auditory TID learning also transfers to and optimizes visual TID with additional practice of an orthogonal near-threshold visual contrast discrimination task at the same trained interval. Practicing these functionally orthogonal tasks per se has no impact on TID thresholds. We interpret the transfer results as indications of a supramodal representation of subsecond time. Moreover, because TID learning shows complete transfer between modalities with vastly different temporal precisions, the sub-second time presentation must be conceptual. Double training may refine this supramodal and conceptual subsecond time representation and connect it to a new sense to improve time perception.

Abstract Introduction Nalbuphine can relieve patients’ inflammation response after surgery compared to other opioid drugs. However, its molecular mechanism has not been clear. Activation of NF-κB signaling pathway under oxidative stress and inflammation can maintain pain escalation. Methods We firstly investigated the effect of nalbuphine on writhing test and mechanical allodynia using a rat model of inflammatory visceral pain (acetic acid (AA) administrated). Cytokines (including tumor necrosis factor (TNF)-α, Interleukin (IL)-1β, IL-2, and IL-6 in plasma were tested with ELISA technology. Expression levels of TNF-α, IκBα and p-NF-κB p65 at the spinal cord (L3–5) were measured by western blot or RT-qPCR. Results We found that the paw withdrawal threshold (PWT) values of rats were reduced in the model group, while the numbers of writhing, levels of IL-1β, IL-2, IL-6, and TNF-α in plasma, and p-NF-κB protein and its gene expressions in the lumbar spinal cord were up-regulated. Subcutaneously injection of nalbuphine (10 μg/kg) or PDTC (NF-κB inhibitor) attenuated acetic acid-induced inflammatory pain, and this was associated with reversal of up-regulated IL-1β, IL-2, IL-6, and TNF-α in both plasma and spinal cord. Furthermore, acetic acid increased p-NF-κB and TNF-α protein levels in the white matter of the spinal cord, which was attenuated by nalbuphine. These results suggested that nalbuphine can significantly ameliorate inflammatory pain via modulating the expression of NF-κB p65 as well as inflammation factors level in the spinal cord. Conclusion In conclusion, nalbuphine inhibits inflammation through down-regulating NF-κB pathway at the spinal cord in a rat model of inflammatory visceral pain.

ObjectiveTo evaluate the diagnostic performance of different ultrasound sections of thyroid nodule (TN) using computer-aided diagnosis system based on artificial intelligence (AI-CADS) in predicting thyroid malignancy.Materials and methodsThis is a retrospective study. From January 2019 to July 2019, patients with preoperative thyroid ultrasound data and postoperative pathological results were enrolled, which were divided into two groups: lower risk group (ACR TI-RADS 1, 2 and 3) and higher risk group (ACR TI-RADS 4 and 5). The malignant risk scores (MRS) of TNs were obtained from longitudinal and transverse sections using AI-CADS. The diagnostic performance of AI-CADS and the consistency of each US characteristic were evaluated between these sections. The receiver operating characteristic (ROC) curve and the Cohen κ-statistic were performed.ResultsA total of 203 patients (45.61 ± 11.59 years, 163 female) with 221 TNs were enrolled. The area under the ROC curve (AUC) of criterion 3 [0.86 (95%CI: 0.80~0.91)] was lower than criterion 1 [0.94 (95%CI: 0.90~ 0.99)], 2 [0.93 (95%CI: 0.89~0.97)] and 4 [0.94 (95%CI: 0.90, 0.99)] significantly (P0.60).ConclusionThe diagnostic performance of computer-aided diagnosis system based on artificial intelligence (AI-CADS) in longitudinal and transverse ultrasonic views for differentiating thyroid nodules (TN) was different, which was higher in the transverse section. It was more dependent on the section for the AI-CADS diagnosis of suspected malignant TNs.

IntroductionPost-traumatic coagulopathy (PTC) is a critical pathology in traumatic brain injury (TBI), however, its potential mechanism is not clear. To explore this in peripheral samples, we integrated single cell RNA-sequencing and T cell repertoire (TCR)-sequencing across a cohort of patients with TBI.MethodsClinical samples from patients with more brain severity demonstrated overexpression of T cell receptor–encoding genes and less TCR diversity.ResultsBy mapping TCR clonality, we found patients with PTC have less TCR clones, and the TCR clones are mainly distributed in cytotoxic effector CD8+T cell. In addition, the counts of CD8+ T cell and natural killer (NK) cells are associated with the coagulation parameter by WGCNA, and the granzyme and lectin-like receptor profiles are also decreased in the peripheral blood from TBI patients, suggesting that reduced peripheral CD8+ clonality and cytotoxic profiles may be involved in PTC after TBI.ConclusionOur work systematically revealed the critical immune status in PTC patients at the single-cell level.

To study the characteristics of sandstone crack propagation under hydraulic coupling, sandstone laboratory tests were conducted under different seepage pressures and confining pressures. Under the same effective confining pressure, it is shown that the rock brittleness index becomes higher as the seepage pressure increases, while the crack initiation stress, the crack damage stress, and the peak stress decrease gradually. The initial volumetric strain of the crack decreases, and the volumetric strain of crack propagation decreases firstly and then increases afterward. The growth rate of the crack axial strain and the crack circumferential strain are both increasing that corresponding to the damage stress and the peak stress, however, no obvious relation is observed between the growth rate of the crack volume strain and the seepage pressure. Under the same seepage pressure, the initiation stress, damage stress, and peak stress gradually increase as the effective confining pressure increases. In addition, the growth rates of the crack axial strain, circumferential strain and volumetric strain increase gradually during deformation that corresponds to the crack initiation stress, damage stress and peak stress, respectively. When comparing the different growth rates of crack strain for a tested sandstone specimen, it is found that the strain growth rates have the following order: the crack axial strain > the crack circumferential strain > the crack volume strain.

BackgroundChronic orofacial pain is a common and incompletely defined clinical condition. The role of G protein-coupled estrogen receptor 1 (GPER1) as a new estrogen receptor in trunk and visceral pain regulation is well known. Here, we researched the role of GPER1 in the rostral ventral medulla (RVM) during chronic orofacial pain.Methods and ResultsA pain model was established where rats were injected in the temporomandibular joint with complete Freund’s adjuvant (CFA) to simulate chronic orofacial pain. Following this a behavioral test was performed to establish pain threshold and results showed that the rats injected with CFA had abnormal pain in the orofacial regions. Additional Immunostaining and blot analysis indicated that microglia were activated in the RVM and GPER1 and c-Fos were significantly upregulated in the rats. Conversely, when the rats were injected with G15 (a GPER1 inhibitor) the abnormal pain the CFA rats were experiencing was alleviated and microglia activation was prevented. In addition, we found that G15 downregulated the expression of phospholipase C (PLC) and protein kinase C (PKC), inhibited the expression of GluA1, restores aberrant synaptic plasticity and reduces the overexpression of the synapse-associated proteins PSD-95 and syb-2 in the RVM of CFA rats.ConclusionThe findings indicate that GPER1 mediates chronic orofacial pain through modulation of the PLC-PKC signal pathway, sensitization of the RVM region and enhancement of neural plasticity. These results of this study therefore suggest that GPER1 may serve as a potential therapeutic target for chronic orofacial pain.

BackgroundHigh-flow nasal oxygenation (HFNO) has been suggested as an alternative oxygenation method during procedural sedation. This randomized, non-inferiority trial evaluated the safety and efficacy of HFNO compared with laryngeal mask airway (LMA) in pediatric ambulatory oral surgery under deep sedation.MethodsIn total, 120 children aged 2–7 years (weight: 10–30 kg) were equally assigned into two groups, namely, HFNO with propofol total intravenous anesthesia infusion (HFNO-IV) or LMA with propofol total intravenous anesthesia infusion (LMA-IV). The primary objective was to monitor carbon dioxide (CO2) accumulation during perioperative surgery. Secondary objectives included monitoring transcutaneous oxygen saturation, grade exposure to the surgical field, perioperative adverse events, or other events. The predefined non-inferiority margin was 7 mmHg. During the COVID-19 pandemic, a novel WeChat applet was implemented to gather follow-up data after discharge.ResultsNon-inferiority could be declared for HFNO relative to LMA (mean difference in transcutaneous CO2 (TcCO2) = −1.4 mmHg, 95% CI: −2.9, 0.1 mmHg; P > 0.05). The pre-surgical TcCO2 of the HFNO-IV group (45.4 ± 4.5 mmHg) was similar to that of the LMA-IV group (44.0 ± 3.5 mmHg), within the clinically acceptable normal range. All the children maintained SpO2 levels of >97%. The surgical field exposure score of the HFNO group was significantly better than that of the LMA group. There was no significant difference between the two groups regarding risk or adverse events.ConclusionHFNO was not inferior to LMA for maintaining oxygenation and ventilation in patients undergoing pediatric ambulatory oral surgery under deep sedation under strict isolation from the oral cavity to the upper airway.

Phosphorus (P) is critical for vegetation growth and ecosystem productivity. P distribution and allocation patterns of plants in natural communities are associated with their resource allocation strategies. However, owing to the lack of systematic research, the spatial variations of vegetation P on the Tibetan Plateau (TP) remain unclear. Based on the 0.5° standardized spatial grid sampling method and survey data obtained from plant organs (leaf, branch, trunk, and root) in 2,040 plant communities, we analyzed the distribution of vegetation P contents (g kg−1) and densities (g P m−2) on the TP. The results indicate that the vegetation P contents and densities differed significantly among the plant organs on the TP. Active organs contained higher P contents but lower P densities. Radiation dominated vegetation P storage and allocation on the TP. Strong radiation had a negative effect on vegetation P accumulation and caused more P to be allocated to the underground parts. The TP vegetation stored approximately 3.64 Tg of P, of which approximately 1.68, 1.28, 0.68, and 0.01 Tg of P were stored in forests, shrublands, grasslands, and deserts, respectively. Based on a large survey dataset, we determined the spatial distributions of vegetation P and constructed a P density distribution map for TP vegetation, which can be used for ecosystem modeling.

In order to identify the distribution pattern of radionuclides in the surface soil in the area of a sandstone-type uranium deposit, and to explore its spatial relationship with the location of the orebody, soil radon measurements and ground gamma-ray spectroscopy were carried out in the Barun study area, and soil properties were analyzed. The results show that the soil radon concentrations exhibited a bimodal feature, while the uranium content showed a decreasing trend along the tendency direction of the orebody. In the ground projection area of the orebody, radon concentration showed a positive correlation with uranium content, with both showing relatively low values. Combined with the results of field geological observation and soil property analysis, it is believed that the relatively low radon concentration and uranium content above the orebody is related to the soil being mainly sandy soil. Relatively high uranium values are distributed within approximately 1.5 km north of the northern boundary of the orebody and near the southern boundary of the orebody. High-value radon anomalies occur within about 2 km north of the northern boundary of the orebody and within about 1.3 km south of the southern boundary of the orebody.

This study aimed to investigate the differences in the relationship between radon and its progeny concentrations and particulate matter concentrations under varying pollution weather conditions. Outdoor radon and its progeny concentrations were measured by a radon/thoron- and radon/thoron progeny monitor (ERS-RDM-2S) during haze and dust storm weather in Beijing. Particulate matter concentrations and meteorological data were simultaneously recorded. Results showed that radon and its progeny concentrations exhibited a diurnal variation pattern, with a minimum in the late afternoon and a maximum in the early morning. The average radon concentrations were similar under both pollution weather conditions, but significantly higher than the reported average for Beijing. The equilibrium equivalent radon concentration during haze was about two times that during a dust storm. PM10 concentrations were similar in both pollution weather conditions, but PM2.5 concentrations during haze were approximately 2.6 times higher than that during dust storms. A positive correlation was observed between radon and its progeny concentrations and particulate matter concentrations, but the correlation was significantly higher during haze than during dust storms. The higher PM2.5 concentration during haze significantly increased the correlation between radon and its progeny concentrations and particulate matter concentrations. We recommended protecting against radon exposure during pollutant weather, especially haze.

The true triaxial loading and unloading tests on granite were conducted to obtain the mechanical characteristics of the granite in the construction area of an underground cavern. The stability of the surrounding rock, the characteristic stress, the failure mode and the brittleness characteristics were mainly analyzed in this work. In addition, the evolution laws of total energy and dissipated energy with axial strain were explored. Results show that under the true triaxial loading and unloading stress paths, the failure modes of granite are both tensile and shear composite failure, and characteristics of high damage stress and brittleness are obviously observed. A new brittleness index is proposed to evaluate rock brittleness by using volumetric strain curve. It is found that the brittleness of granite is higher under unloading conditions. In the true triaxial loading test, the change trend of total energy with axial strain goes through three stages: slow increase, rapid increase, and steady increase. In the true triaxial unloading test, the dissipated energy increases rapidly at the moment of unloading, and its proportion in the energy distribution exceeds the elastic strain energy, which becomes the main energy consumption. The energy dissipation value of the granite sample in the loading test is obviously greater than that in the unloading test. It indicates that more energy is required for samples under the loading path to produce damage, which is safer than the unloading path. The particle flow PFC3D is used to simulate the true triaxial loading and unloading test of granite in this study. The failure mode and the crack distribution of the numerical simulation results are basically consistent with results of the laboratory test. Then the numerical model is used to simulate the rapid unloading failure process of granite. It is found that the rock sample particle ejection damage will occur at the end of the model, similar to a rock burst.

Abstract Background Due to the inherent characteristics of immersion, imagination, and interactivity in virtual reality (VR), it might be suitable for non-drug behavior management of children in dental clinics. The purpose of this trial was to measure the role of VR distraction on behavior management in short-term dental procedures in children. Methods A randomized clinical trial design was carried out on 120 children aged between 4 and 8 years to identify the comparative efficacy of VR and tell-show-do (TSD) to improve behavioral management during dental procedures. The primary outcomes were evaluated anxiety, pain, and compliance scores in perioperative children. The levels of operative anxiety and pain were assessed using the Children’s Fear Survey Schedule-Dental Subscale (CFSS-DS) and Wong Baker FACES Pain Rating Scale (WBFS), respectively. The Frankl Behavior Rating Scale (FBRS) was tested before and during dental procedures. The length of the dental procedure was compared between both groups after treatment. Results The average anxiety and behavioral scores of the VR group significantly reduced compared with the control. The decreased anxiety score for the VR group and control group were 8 (7, 11) and 5 (5, 7), p < 0.05. The compliance scores of the control group during treatment were 3 (2, 3), and the same in the VR intervention were 3 (3, 4), p = 0.02. A significant reduction in pain was observed when using VR distraction (p < 0.05). Comparing the length of the dental procedure, the VR group (19.0 2 ± 5.32 min) had a shorter treatment time than the control group (27.80 ± 10.40 min). Conclusion The use of VR significantly reduced the anxiety and pain of children and the length of the dental procedure and improved the compliance of children that underwent short-term dental procedures without an adverse reaction. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029802 . Registered on February 14, 2020

Among the world's 10 major gas producing countries, only the United States (USA), Russia and Iran have annual gas production of 250 × 109 m3 or more. China is expected to have gas output of 250 × 109 m3 in 2025. There are three advantages for the great development of natural gas industry in China. Firstly, the natural gas resources are rich and the proved rate is low and only 8.6%, so it has the resource advantage for faster development; Secondly, over the past 35 years, natural gas production continues to grow, with the growth advantage for faster development; Finally, since 2006, the remaining recoverable reserves of natural gas have been increasing year by year, showing the reserve advantage for faster development. In recent 10 years, China's annual natural gas production growth rate, remaining recoverable reserves and reserve-production ratio of natural gas support that China's annual gas production in 2025 will reach 250 × 109 m3. Suggestions for accelerating natural gas exploration and development during the 14th Five-Year Plan Period: (1) Opening new exploration and development fields of Carboniferous-Permian shale gas in the Ordos Basin; (2) Exploring three potential large gas districts with hidden coal measures in the northern Tianshan Piedown Depression, Qaidam Depression, and Xihu Sag; (3) Accelerating the development of seven large gas fields with proved reserves over 100 × 109 m3, such as Lingshui 17–2 Gas Field; (4) Increasing the drilling of gas wells and ultra-deep exploration wells.

Abstract Although synergistic therapy has shown great promise for effective treatment of cancer, the unsatisfactory therapeutic efficacy of photothermal therapy/photodynamic therapy is resulted from the absorption wavelength mismatch, tumor hypoxia, photosensitizer leakage, and inability in intelligent on‐demand activation. Herein, based on the characteristics of tumor microenvironment (TME), such as the slight acidity, hypoxia, and overexpression of H2O2, a TME stimuli‐responsive and dual‐targeted composite nanoplatform (UCTTD‐PC4) is strategically explored by coating a tannic acid (TA)/Fe3+ nanofilm with good biocompatibility onto the upconversion nanoparticles in an ultrafast, green and simple way. The pH‐responsive feature of UCTTD‐PC4 remains stable during the blood circulation, while rapidly releases Fe3+ in the slightly acidic tumor cells, which results in catalyzing H2O2 to produce O2 and overcoming the tumor hypoxia. Notably, the emission spectrum of the UCTTD perfectly matches the absorption spectrum of the photosensitizer (perylene probe (PC4)) to achieve the enhanced therapeutic effect triggered by a single laser. This study provides a new strategy for the rational design and development of the safe and efficient single near‐infrared laser‐triggered synergistic treatment platform for hypoxic cancer under the guidance of multimodal imaging.

ObjectivesNew ventilation modes have been proposed to support the perioperative treatment of patients with obesity, but there is a lack of consensus regarding the optimal strategy. Therefore, a network meta-analysis update of 13 ventilation strategies was conducted to determine the optimal mode of mechanical ventilation as a protective ventilation strategy decreases pulmonary atelectasis caused by inflammation.MethodsThe following databases were searched: MEDLINE; Cochrane Library; Embase; CINAHL; Google Scholar; and Web of Science for randomized controlled trials of mechanical ventilation in patients with obesity published up to May 1, 2022.ResultsVolume-controlled ventilation with individualized positive end-expiratory pressure and a recruitment maneuver (VCV+PEEPind+RM) was found to be the most effective strategy for improving ratio of the arterial O2 partial pressure to the inspiratory O2 concentration (PaO2/FiO2), and superior to pressure-controlled ventilation (PCV), volume-controlled ventilation (VCV), volume-controlled ventilation with recruitment maneuver (VCV+RM), volume-controlled ventilation with low positive end-expiratory pressure (VCV+lowPEEP), volume-controlled ventilation with lower positive expiratory end pressure (PEEP) and recruitment maneuver (VCV+lowPEEP+RM), and the mean difference [MD], the 95% confidence intervals [CIs] and [quality of evidence] were: 162.19 [32.94, 291.45] [very low]; 180.74 [59.22, 302.27] [low]; 171.07 [40.60, 301.54] [very low]; 135.14 [36.10, 234.18] [low]; and 139.21 [27.08, 251.34] [very low]. Surface under the cumulative ranking curve (SUCRA) value showed VCV+PEEPind+RM was the best strategy for improving PaO2/FiO2 (SUCRA: 0.963). VCV with high positive PEEP and recruitment maneuver (VCV+highPEEP+RM) was more effective in decreasing postoperative pulmonary atelectasis than the VCV+lowPEEP+RM strategy. It was found that volume-controlled ventilation with high positive expiratory end pressure (VCV+highPEEP), risk ratio [RR] [95% CIs] and [quality of evidence], 0.56 [0.38, 0.81] [moderate], 0.56 [0.34, 0.92] [moderate]. SUCRA value ranked VCV+highPEEP+RM the best strategy for improving postoperative pulmonary atelectasis intervention (SUCRA: 0.933). It should be noted that the quality of evidence was in all cases very low or only moderate.ConclusionsThis research suggests that VCV+PEEPind+RM is the optimal ventilation strategy for patients with obesity and is more effective in increasing PaO2/FiO2, improving lung compliance, and among the five ventilation strategies for postoperative atelectasis, VCV+highPEEP+RM had the greatest potential to reduce atelectasis caused by inflammation.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288941.

BackgroundOral dental treatment cause anxiety, fear, and physical stress. This study aimed to investigate the efficacy and safety of moderate sedation by remimazolam with alfentanil vs. propofol with alfentanil in third molar extraction.MethodsThis single-center, randomized, single-blind clinical trial included 100 adults who underwent third molar ambulatory extraction. All patients had continuous infusion of Alfentanil 0.2 μg/kg/min. Group remimazolam with alfentanil (group RA) had an induction dose of 80 μg/kg and maintenance dosage of 5 μg/kg/min. In group propofol with alfentanil (PA group), propofol was infused at an initial concentration of 1.8 μg/mL under target controlled infusion (TCI) mode and a maintenance concentration of 1.5 μg/mL. The incidence rates of adverse effects were recorded and compared. Depth of sedation was assessed using the modified observer alertness/sedation assessment (MOAA/S) and entropy index. Recovery characteristics were recorded and complications observed for next 24 h.ResultsThe incident of adverse events 6 (12%) in the group RA was lower than the group PA 25 (50%) [Mean difference 0.136 (95%CI, 0.049–0.377); P < 0.05], with no serious adverse events during the sedation procedure. The incidence of injection pain in group RA was significantly lower than that in group PA [4 vs. 26%, mean difference 0.119 (95%CI, 0.025–0.558); P = 0.004]. Before starting local anesthesia, the mean arterial pressure, heart rate, and respiratory rate of the PA group were lower than those of the RA group. None of the patients required further treatments for a decreased heart rate, blood pressure, or low SpO2. The rate of moderate sedation success was 100% in both groups. The MOAA/S score was similar between the groups indicating that the depth of sedation was effective. Group RA had significantly shorter recovery and discharge times than those of group PA.ConclusionsRemimazolam with alfentanil is a safer and more effective alternative for ambulatory sedation and can reduce recovery and discharge time and the incidence of perioperative adverse events compare with propofol.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier: ChiCTR2200058106.