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Abstract An electroreductive strategy for radical hydroxyl fluorosulfonylation of alkenes with sulfuryl chlorofluoride and molecular oxygen from air is described. This mild protocol displays excellent functional group compatibility, broad scope, and good scalability, providing convenient access to diverse β-hydroxy sulfonyl fluorides. These β-hydroxy sulfonyl fluoride products can be further converted to valuable aliphatic sulfonyl fluorides, β-keto sulfonyl fluorides, and β-alkenyl sulfonyl fluorides. Further, some of these products showed excellent inhibitory activity against Botrytis cinerea or Bursaphelenchus xylophilus, which could be useful for potent agrochemical discovery. Preliminary mechanistic studies indicate that this transformation is achieved through rapid O2 interception by the alkyl radical and subsequent reduction of the peroxy radical, which outcompete other side reactions such as chlorine atom transfer, hydrogen atom transfer, and Russell fragmentation.

Abstract Whether CD8+ T lymphocytes control human immunodeficiency virus infection by cytopathic or non-cytopathic mechanisms is not fully understood. Multiple studies highlighted non-cytopathic effects, but one hypothesis is that cytopathic effects of CD8+ T cells occur before viral production. Here, to examine the role of CD8+ T cells prior to virus production, we treated SIVmac251-infected macaques with an integrase inhibitor combined with a CD8-depleting antibody, or with either reagent alone. We analyzed the ensuing viral dynamics using a mathematical model that included infected cells pre- and post- viral DNA integration to compare different immune effector mechanisms. Macaques receiving the integrase inhibitor alone experienced greater viral load decays, reaching lower nadirs on treatment, than those treated also with the CD8-depleting antibody. Models including CD8+ cell-mediated reduction of viral production (non-cytolytic) were found to best explain the viral profiles across all macaques, in addition an effect in killing infected cells pre-integration (cytolytic) was supported in some of the best models. Our results suggest that CD8+ T cells have both a cytolytic effect on infected cells before viral integration, and a direct, non-cytolytic effect by suppressing viral production.

ObjectiveSelf-management is crucial in managing recurrent pregnancy loss (RPL). This study explored the knowledge, attitudes, and practices (KAP) of patients with RPL toward RPL.MethodsThis cross-sectional study was conducted among patients with RPL between January 2023 and June 2023 at the Second Hospital of Lanzhou University. Participants’ demographic characteristics and KAP were determined using a self-designed questionnaire (Cronbach’s α = 0.818). Structural equation modeling (SEM) was used to observe the correlations among KAP and different factors.ResultsThis study analyzed 497 valid questionnaires. The mean knowledge, attitude, and practice scores were 11.59 ± 4.30 (possible range: 0–20, 57.95%), 44.17 ± 3.18 (possible range: 13–65, 67.95%), and 32.39 ± 5.22 (possible range: 8–40, 80.98%), indicating poor knowledge, moderate attitude, and proactive practice. Age was non-linearly associated with the KAP dimensions, with a positive impact of age on KAP among those aged

Minimally invasive techniques have been widely applied in general thoracic surgery. Compared with video-assisted thoracoscopic surgery (VATS), due to its theoretic superiority, robotic surgery is challenging the traditional position of VATS. With its unique advantages, including 3D vision and a high-freedom endowrist, it leads to easier lymph node dissection, more convenient blood vessel dissection, a shorter learning curve and competence for the completion of complex surgery. However, as a new surgical technology, the safety and efficacy of robotic-assisted thoracoscopic surgery (RATS) still need to be further verified. Thus, in this article, we review and summarize the application of RATS versus VATS in general thoracic surgery.

HIV infection results in the depletion of CD4+ T cells overtime and the loss of coordinated cellular immunity, but how this corresponds to the SIV infected African Green Monkey (AGM) model of non-progressive disease is not known. Here the authors assess the impact of experimental CD4+ T cell depletion in AGM and show that lack of disease progression and resistance to AIDS in this model are independent of CD4+ T cell loss.

Resolution of T cell activation and inflammation is a key determinant of the lack of SIV disease progression in African green monkeys (AGMs). Although frequently considered together, T cell activation occurs in response to viral stimulation of acquired immunity, while inflammation reflects innate immune responses to mucosal injury. We dissociated T cell activation from inflammation through regulatory T cell (Treg) depletion with Ontak (interleukin-2 coupled with diphtheria toxin) during early SIV infection of AGMs. This intervention abolished control of T cell immune activation beyond the transition from acute to chronic infection. Ontak had no effect on gut barrier integrity, microbial translocation, inflammation, and hypercoagulation, despite increasing T cell activation. Ontak administration increased macrophage counts yet decreased their activation. Persistent T cell activation influenced SIV pathogenesis, shifting the ramp-up in viral replication to earlier time points, prolonging the high levels of replication, and delaying CD4+ T cell restoration yet without any clinical or biological sign of disease progression in Treg-depleted AGMs. Thus, by inducing T cell activation without damaging mucosal barrier integrity, we showed that systemic T cell activation per se is not sufficient to drive disease progression, which suggests that control of systemic inflammation (likely through maintenance of gut integrity) is the key determinant of lack of disease progression in natural hosts of SIVs.

Summary: Systemic metabolites serving as danger-associated molecular patterns play crucial roles in modulating the development, differentiation, and activity of innate immune cells. Yet, it is unclear how innate immune cells detect systemic metabolites for signal transmission. Here, we show that bile acids function as endogenous mitofusin 2 (MFN2) ligands and differentially modulate innate immune response to bacterial infection under cholestatic and physiological conditions. Bile acids at high concentrations promote mitochondrial tethering to the endoplasmic reticulum (ER), leading to calcium overload in the mitochondrion, which activates NLRP3 inflammasome and pyroptosis. By contrast, at physiologically relevant low concentrations, bile acids promote mitochondrial fusion, leading to enhanced oxidative phosphorylation and thereby strengthening infiltrated macrophages mediated phagocytotic clearance of bacteria. These findings support that bile acids, as endogenous activators of MFN2, are vital for tuning innate immune responses against infections, representing a causal link that connects systemic metabolism with mitochondrial dynamics in shaping innate immunity.

BackgroundNon-small cell lung cancer (NSCLC) is still of concern in differentiating it from benign disease. This study aims to validate the diagnostic efficacy of a novel seven-autoantibody (7-AAB) panel for the diagnosis of NSCLC.MethodsWe retrospectively enrolled 2650 patients who underwent both the 7-AAB panel test and CT scanning. We compared the sensitivity, specificity, and PPV of 7-AAB, CT, and PET-CT in the diagnosis of NSCLC in different subgroups. Then, we established a nomogram based on CT image features and the 7-AAB panel to further improve diagnostic efficiency. Moreover, we compared the pathological and molecular results of NSCLC patients in the 7-AABs positive group and the negative group to verify the prognostic value of the 7-AAB panel.ResultsThe strategy of a “both-positive rule” combination of 7-AABs and CT had a specificity of 95.4% and a positive predictive value (PPV) of 95.8%, significantly higher than those of CT or PET-CT used alone (P0.05) with an AUC of 0.791. Interestingly, it was found that the 7-AABs positive group was associated with higher proportion of EGFR mutations (P

Compared to more developed countries, the use of land resources is less efficient in China. China’s vast forest land area gives it a rich and underutilized carbon sink. This is an important way for China to achieve the goals of “carbon peaking” and “carbon neutrality”, which is of great significance to China’s sustainable development. In the past 20 years, China has designed a series of policies to serve the development of forestry carbon sinks, namely the forestry carbon sink mechanism (FCSM). However, the questions of which policy is the most important, and what is the socio-economic value it generates, have not been fully investigated. Accordingly, this paper studied 30 provincial-level regions in China from 2005 to 2020 using the difference-in-differences (DID) model. The conclusions show that: (1) the FCSM does increase the socio-economic value of land resources, thus improving the sustainability of land resources; (2) the FCSM helps to increase forest coverage, forest stock volume and the forest coverage rate, which increases the social value of land resources from the greening path; (3) the FCSM helps to increase the gross forestry product, which increases the economic value of land resources through the path of increasing production value.

In this paper, we study the problem of privacy-preserving data synthesis (PPDS) for tabular data in a distributed multi-party environment. In a decentralized setting, for PPDS, federated generative models with differential privacy are used by the existing methods. Unfortunately, the existing models apply only to images or text data and not to tabular data. Unlike images, tabular data usually consist of mixed data types (discrete and continuous attributes) and real-world datasets with highly imbalanced data distributions. Existing methods hardly model such scenarios due to the multimodal distributions in the decentralized continuous columns and highly imbalanced categorical attributes of the clients. To solve these problems, we propose a federated generative model for decentralized tabular data synthesis (HT-Fed-GAN). There are three important parts of HT-Fed-GAN: the federated variational Bayesian Gaussian mixture model (Fed-VB-GMM), which is designed to solve the problem of multimodal distributions; federated conditional one-hot encoding with conditional sampling for global categorical attribute representation and rebalancing; and a privacy consumption-based federated conditional GAN for privacy-preserving decentralized data modeling. The experimental results on five real-world datasets show that HT-Fed-GAN obtains the best trade-off between the data utility and privacy level. For the data utility, the tables generated by HT-Fed-GAN are the most statistically similar to the original tables and the evaluation scores show that HT-Fed-GAN outperforms the state-of-the-art model in terms of machine learning tasks.

Lung cancer is the most common cancer and the leading cause of cancer death in the world, among which non-small cell lung cancer (NSCLC) accounts for about 85% of the total lung cancer. With the widespread of computed tomography (CT) and other imaging screening methods, the pathological types of lung cancer have changed from central squamous cell carcinoma to the early-stage lung adenocarcinoma, which is manifested as isolated pulmonary nodules and ground glass nodules on CT. Early diagnosis and treatment of lung cancer is of crucial clinical significance, and the continuous development and improvement of minimally invasive interventional techniques provide more options for lung cancer treatment, such as stereotactic radiation, percutaneous ablation, and bronchial intervention. This paper will make a review on the principle, advantages, disadvantages and prospects of minimally invasive interventional therapy commonly used in clinical practice.

The Phosphatase and tensin homolog (PTEN) gene is one of the most important tumor suppressor genes, which acts through its unique protein phosphatase and lipid phosphatase activity. PTEN protein is widely distributed and exhibits complex biological functions and regulatory modes. It is involved in the regulation of cell morphology, proliferation, differentiation, adhesion, and migration through a variety of signaling pathways. The role of PTEN in malignant tumors of the digestive system is well documented. Recent studies have indicated that PTEN may be closely related to many other benign processes in digestive organs. Emerging evidence suggests that PTEN is a potential therapeutic target in the context of several non-neoplastic diseases of the digestive tract. The recent discovery of PTEN isoforms is expected to help unravel more biological effects of PTEN in non-neoplastic digestive diseases.

In recent years, the investigation of leader tortuosity in long air discharge is brought into focus, for it is the main factor that influents the 50% breakdown voltage and can be used to validate and test the discharge modes in the design of long air gap dimension. In order to find out whether the test data of the whole leader channels are accuracy to represent the leader propagation paths, a discharge test of a 4 m rod-plane air gap subjected to switching impulse voltage is carried out. And an observation platform is set up to synchronously record the voltage waveforms, the discharge currents, the leader propagation processes and the whole leader channels. A new method is proposed to subtract the final-jump part from the whole leader channel by identifying the leader tip height at the initiation of the final jump (LTH for short) from the CCD image. Then the test data of LTH and the leader propagation path are statistically obtained. And probability density functions (PDFs for short) of three different angles between consecutive segments of the leader propagation path are used to quantitatively describe the leader tortuosity. According to the analysis of the results, the mean value of LTH is nearly half the gap length in the gap axial direction. And an obvious difference can be discovered when comparing PDFs of the leader propagation paths with those of the whole leader channels. A conclusion to account for the difference is deduced that the leader paths during the final jump are much straighter than those during leader propagation. In the end, the present work recommends that the final-jump part should be subtracted from the whole leader channel when the test data of leader tortuosity are used in the numerical model for positive long air discharge.

Coal-fired power plants are widely used to achieve a power balance in grids with renewable energy, which leads to new requirements for speediness in load dispatch. This paper presents a nondominated-sorting grey wolf optimizer algorithm (NSGWO) for the multiobjective load dispatch of coal-fired power plants that employed efficient nondominated sorting, a reference-point selection strategy, and a simulated binary crossover operator. The optimization results of the benchmark functions indicated that the NSGWO algorithm had a better accuracy and a better distribution than the traditional multiobjective grey wolf optimizer algorithm. Regarding the load dispatch of economy, environmental protection, and speediness strategies, the NSGWO had the best performance of all the simulated algorithms. The optimal-compromise solutions of the economy and speediness strategies of the NSGWO algorithm had a good distribution, which elucidated that this novel algorithm was favorable to allowing coal-fired power plants to accommodate renewable energy.

Viruses that persist despite seemingly effective antiretroviral treatment (ART) and can reinitiate infection if treatment is stopped preclude definitive treatment of HIV-1 infected individuals, requiring lifelong ART. Among strategies proposed for targeting these viral reservoirs, the premise of the "shock and kill" strategy is to induce expression of latent proviruses [for example with histone deacetylase inhibitors (HDACis)] resulting in elimination of the affected cells through viral cytolysis or immune clearance mechanisms. Yet, ex vivo studies reported that HDACis have variable efficacy for reactivating latent proviruses, and hinder immune functions. We developed a nonhuman primate model of post-treatment control of SIV through early and prolonged administration of ART and performed in vivo reactivation experiments in controller RMs, evaluating the ability of the HDACi romidepsin (RMD) to reactivate SIV and the impact of RMD treatment on SIV-specific T cell responses. Ten RMs were IV-infected with a SIVsmmFTq transmitted-founder infectious molecular clone. Four RMs received conventional ART for >9 months, starting from 65 days post-infection. SIVsmmFTq plasma viremia was robustly controlled to

Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

In rhesus macaques (RMs), experimental depletion of CD4+ T-cells prior to SIV infection results in higher viremia and emergence of CD4-independent SIV-envelopes. In this study we used the rhesus recombinant anti-CD4 antibody CD4R1 to deplete RM CD4+ T-cells prior to SIVmac251 infection and investigate the sources of the increased viral burden and the lifespan of productively infected cells. CD4-depleted animals showed (i) set-point viral load two-logs higher than controls; (ii) macrophages constituting 80% of all SIV vRNA+ cells in lymph node and mucosal tissues; (iii) substantial expansion of pro-inflammatory monocytes; (iv) aberrant activation and infection of microglial cells; and (v) lifespan of productively infected cells significantly longer in comparison to controls, but markedly shorter than previously estimated for macrophages. The net effect of CD4+ T-cell depletion is an inability to control SIV replication and a shift in the tropism of infected cells to macrophages, microglia, and, potentially, other CD4-low cells which all appear to have a shortened in vivo lifespan. We believe these findings have important implications for HIV eradication studies.