Blood-Brain Barrier Penetrating Nanovehicles for Interfering with Mitochondrial Electron Flow in Glioblastoma.

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of human brain tumors. Dismantling the suppressed immune microenvironment is an effective therapeutic strategy against GBM; however, GBM does not respond to exogenous immunotherapeutic agents due to low immunogenicity. Manipulating the mitochondrial electron transport chain (ETC) elevates the immunogenicity of GBM, rendering previously immune-evasive tumors highly susceptible to immune surveillance, thereby enhancing tumor immune responsiveness and subsequently activating both innate and adaptive immunity. Here, we report a nanomedicine-based immunotherapeutic approach that targets the mitochondria in GBM cells by utilizing a Trojan-inspired nanovector (ABBPN) that can cross the blood-brain barrier. We propose that the synthetic photosensitizer IrPS can alter mitochondrial electron flow and concurrently interfere with mitochondrial antioxidative mechanisms by delivering si-OGG1 to GBM cells. Our synthesized ABBPN coloaded with IrPS and si-OGG1 (ISA) disrupts mitochondrial electron flow, which inhibits ATP production and induces mitochondrial DNA oxidation, thereby recruiting immune cells and endogenously activating intracranial antitumor immune responses. The results of our study indicate that strategies targeting the mitochondrial ETC have the potential to treat tumors with limited immunogenicity.

Targeting cAMP in D1-MSNs in the nucleus accumbens, a new rapid antidepressant strategy.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Multi-interface Combination of Bimetallic Selenide and V4C3Tx MXene for High-Rate and Ultrastable Sodium Storage Devices.

Sodium-ion batteries (SIBs) have great potential as electrochemical energy storage systems; however, their commercial viability is limited by the lack of anode materials with fast charge/discharge rates and long lifetimes. These challenges were addressed by developing a multi-interface design strategy using FCSe (FeSe2/CoSe2) nanoparticles on V4C3Tx MXene nanosheets as conductive substrates. The heterogeneous interface created between the two materials provided high-speed transport of sodium ions, suppressed the chalking-off of nanoparticles, and improved the cycling stability. Additionally, the Fe-Co bonds generated at the interface effectively relieved mechanical stress, further enhancing the electrode durability. The C@FCSe@V4C3 electrode exhibited high-speed charging and discharging characteristics, and maintained a high specific capacity of 260.5 mAh g-1 even after 15,000 cycles at 10 A g-1, with a capacity retention rate of 50.2% at an ultrahigh current density of 20 A g-1. Furthermore, the composite displayed a good cycling capability in the fast discharge and slow charge mode. This demonstrates its promising commercial potential. This multi-interface design strategy provides insights and guidance for solving the reversibility and cycling problems of transformed selenide anode materials.

Identification and verification of PTPN3 as a novel biomarker in predicting cancer prognosis, immunity, and immunotherapeutic efficacy.

BACKGROUND: The importance of protein tyrosine phosphatase non-receptor type 3 (PTPN3) in controlling multifaceted tumor cell behaviors throughout cancer development has received widespread attention. Nevertheless, little is known about the biological roles of PTPN3 in drug sensitivity, immunotherapeutic effectiveness, tumor immune microenvironment, and cancer prognosis. METHODS: The Cancer Genome Atlas (TCGA) database's RNAseq data were used to examine the expression of PTPN3 in 33 different cancer types. In addition, immunohistochemistry (IHC) was performed to validate the expression of PTPN3 across various cancer types within our clinical cohorts. The features of PTPN3 alterations were demonstrated throughout the cBioPortal database. This study focused on examining the prognostic and clinicopathological importance of PTPN3 through the acquisition of clinical data from the TCGA database. The investigation of PTPN3's probable role in the tumor immune microenvironment was demonstrated by the application of CIBERSORT, ESTIMATE algorithms, and the TISIDB database. Using Spearman's rank correlation coefficient, the relationships between PTPN3 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) were evaluated. To further investigate the putative biological activities and downstream pathways of PTPN3 in various cancers in humans, Gene Set Enrichment Analysis (GSEA) was carried out. In addition, an examination was conducted to explore the associations between PTPN3 and the effectiveness of PD-1/PD-L1 inhibitors, utilizing data extracted from the GEO database. RESULTS: PTPN3 was abnormally expressed in multiple cancer types and was also strictly associated with the prognosis of cancer patients. IHC was used to investigate and confirm the various expression levels of PTPN3 in various malignancies, including breast cancer, lung cancer, sarcoma, and kidney renal clear cell carcinoma in our clinical cohorts. There is a high correlation between the levels of PTPN3 expression in different cancers and infiltrating immune cells, including mast cells, B cells, regulatory T cells, CD8 + T cells, macrophages, and dendritic cells. Infiltrating immune cells, such as regulatory T cells, CD8 + T cells, macrophages, B cells, dendritic cells, and mast cells, are strongly correlated with PTPN3 expression levels in various tumors. The expression of PTPN3 exhibited a substantial correlation with many immune-related biomolecules and the expression of TMB and MSI in multiple types of cancer. In addition, PTPN3 has demonstrated promise in predicting the therapeutic benefits of PD-1/PD-L1 inhibitors and the susceptibility to anti-cancer medications in the treatment of clinical cancer. CONCLUSIONS: Our findings highlight the importance of PTPN3 as a prognostic biomarker and predictor of immunotherapy success in various forms of cancer. Furthermore, PTPN3 appears to have an important role in modifying the tumor immune microenvironment, highlighting its potential as a promising biomarker for prognosis prediction, immunotherapeutic efficacy evaluation, and identification of immune-related characteristics in diverse cancer types.

Prognostic variations between 'primary' and 'progressive' muscle-invasive bladder cancer following radical cystectomy: a novel propensity score-based multicenter cohort study.

OBJECTIVE: To assess prognostic differences between primary and progressive muscle-invasive bladder cancer (MIBC) following radical cystectomy. MATERIAL AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to abstract MIBC data following radical cystectomy from 2000 to 2019. Patients were classified as either 'Primary' MIBC (defined as the presentation of muscle-invasive disease at initial diagnosis) or 'Progressive' MIBC (defined as a non-muscle invasive disease that later progressed to MIBC). Baseline characteristics for the two groups were balanced using a propensity score overlap weight (PSOW) technique. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Cox's proportional hazard regression was used to assess risk factors associated with overall survival (OS) and cancer-specific survival (CSS). RESULTS: Six thousand six hundred thirty-two MIBC patients were identified in the SEER database. Among them, 83.3% ( n =5658) were considered primary MIBC patients, and 16.7% ( n =974) were categorized as progressive MIBC patients. Distribution of baseline covariates, including age, sex, race, T stage, N stage, tumour grade, marital status, and chemotherapy, were well-balanced after PSOWs were applied. After stable PSOW adjustments, Kaplan-Meier survival analysis showed that the CSS for progressive MIBC [hazard ratio (HR)=1.25, 95% confidence interval (CI): 1.12-1.38, P <0.001) was poorer than the primary MIBC group. However, the difference in OS (HR=1.08, 95% CI: 0.99-1.18) was not significant ( P =0.073). Multivariate analysis also suggested that patients with progressive MIBC have significantly poorer CSS (HR=1.24, 95% CI: 1.19-1.38, P <0.001) but not OS (HR=1.08, 95% CI: 0.99-1.18, P =0.089). CONCLUSION: CSS for progressive MIBC patients appears worse than for those with primary MIBC. This highlights the need to direct more resources for this patient population and particularly for high-risk cases of non-MIBC, where timely radical surgery will improve patients prognoses.

Flexible Ti3 C2 Tx MXene Bonded Bio-Derived Carbon Fibers Support Tin Disulfide for Fast and Stable Sodium Storage.

High energy density and flexible electrodes, which have high mechanical properties and electrochemical stability, are critical to the development of wearable electronics. In this work, a free-standing MXene bonded SnS2 composited nitrogen-doped carbon fibers (MXene/SnS2 @NCFs) film is reported as a flexible anode for sodium-ion batteries. SnS2 nanoparticles with high-capacity properties are covalently decorated in bio-derived nitrogen-doped 1D carbon fibers (SnS2 @NCFs) and further assembled with highly conductive MXene sheets. The addition of bacterial cellulose (BC) can further improve the flexibility of the film. The unique 3D structure of points, lines, and planes can not only offset the disadvantage of low conductivity of SnS2 nanoparticles but also expand the distance between MXene sheets, which is conducive to the penetration of electrolytes. More importantly, the MXene sheets and N-doped 1D carbon fibers (NCFs) can accommodate the large volume expansion of SnS2 nanoparticles and trap polysulfide during the cycle. The MXene/SnS2 @NCFs film exhibits better sodium storage and excellent rate performance compared to the SnS2 @NCFs. The in situ XRD and ex situ (XRD, XPS, and HRTEM) techniques are used to analyze the sodiation process and to deeply study the reaction mechanism of the films. Finally, the quasi-solid-state full cells with MXene/SnS2 @NCFs and Na3 V2 (PO4 )3 @carbon cloth (NVP@CC) fully demonstrate the application potential of the flexible electrodes.

Effect of subsequent bladder cancer on survival in upper tract urothelial carcinoma patients post-radical nephroureterectomy: a systematic review and meta-analysis.

BACKGROUND: Radical nephroureterectomy (RNU) is the primary treatment strategy for upper tract urothelial carcinoma (UTUC). However, the intravesical recurrence occurs in 20-50% of all patients. The specific effect of subsequent bladder cancer (SBCa) on survival remains unclear. Therefore, we investigated the effect of SBCa following RNU in patients with UTUC. METHODS: PubMed, EMBASE, and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between SBCa and without SBCa. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3). RESULTS: Five studies involving 2057 patients were selected according to the predefined eligibility criteria. Meta-analysis of cancer-specific survival (CSS) and overall survival (OS) revealed no significant differences between the SBCa and non-SBCa groups. However, subgroup analysis of pT0-3N0M0 patients suggested that people with SBCa had worse CSS (HR = 5.13, 95%CI 2.39-10.98, p < 0.0001) and OS (HR = 4.00, 95%CI 2.19-7.31, p < 0.00001). CONCLUSIONS: SBCa appears to be associated with worse OS in patients with early stage UTUC. However, caution must be taken before recommendations are made because this interpretation is based on very few clinical studies and a small sample size. Research sharing more detailed surgical site descriptions, as well as enhanced outcome data collection and improved reporting, is required to further investigate these nuances.

Human behavior recognition based on sparse transformer with channel attention mechanism.

Human activity recognition (HAR) has recently become a popular research field in the wearable sensor technology scene. By analyzing the human behavior data, some disease risks or potential health issues can be detected, and patients' rehabilitation progress can be evaluated. With the excellent performance of Transformer in natural language processing and visual tasks, researchers have begun to focus on its application in time series. The Transformer model models long-term dependencies between sequences through self-attention mechanisms, capturing contextual information over extended periods. In this paper, we propose a hybrid model based on the channel attention mechanism and Transformer model to improve the feature representation ability of sensor-based HAR tasks. Extensive experiments were conducted on three public HAR datasets, and the results show that our network achieved accuracies of 98.10%, 97.21%, and 98.82% on the HARTH, PAMAP2, and UCI-HAR datasets, respectively, The overall performance is at the level of the most advanced methods.

Genomic surveillance of SARS-CoV-2 in Weihai, China, march 2022 to march 2023.

COVID-19 is an acute respiratory infectious disease caused by SARS-CoV-2. It was first reported in Wuhan, China in December 2019 and rapidly spread globally in early 2020, triggering a global pandemic. In December 2022, China adjusted the dynamic COVID-zero strategy that lasted for three years. The number of positive cases in China increased rapidly in the short term. Weihai was also affected during this period. We conducted genomic surveillance of SARS-CoV-2 variants in Weihai during this period, hoping to understand the changes in the genomic characteristics of SARS-CoV-2 before and after the adjustment of the epidemic policy. In this study,we collected SARS-CoV-2 positive samples from March 2022 to March 2023 in Weihai and performed SARS-CoV-2 whole genome sequencing on these samples using next-generation sequencing technology. we obtained a total of 704 SARS-CoV-2 whole genome sequences, and selected 581 high-quality sequences for further analysis. The analysis results showed that from March 2022 to November 2022, before the adjustment of epidemic policy, the COVID-19 cases in Weihai were mainly from four local clusters,which were caused by four variants, including BA.2,BA.1.1,P.1.15 and BA.5.2.1. Phylogenetic analysis showed that: In the same cluster,the sequences between each other were highly homologous, and the whole genome sequence were almost identical. After December 2022, the epidemic policy was adjusted, BF.7 and BA.5.2 became the dominant variants in Weihai, consistent with the main domestic strains in China during the same period. Phylodynamic analysis showed that BF.7 and BA.5.2 had a large amount of genetic diversities in December, and the effective population size of BF.7 and BA.5.2 also showed explosive growth in December. In conclusion, we reported the composition and dynamic trend of SARS-CoV-2 variants in Weihai from March 2022 to March 2023. We found that there have been significant changes in the variants and expansion patterns of SARS-CoV-2 before and after the adjustment of epidemic policies. But the dominant variants in Weihai were the same as the SARS-CoV-2 variants circulating globally at the same time and we found no persistently dominant variants or new lineages during this period.

Allium ureteral stent for the treatment of malignant ureteral obstruction: A median term study.

This study aimed to assess the safety and efficacy of Allium ureteral stents for the maintenance therapy of malignant ureteral obstruction (MUO). Clinical data of 25 patients (27 sides) with ureteral obstruction caused by a malignant tumor from December 2018 to December 2021 were retrospectively analyzed. Preoperative ultrasonography and computed tomography urography indicated hydronephrosis and MUO. Allium ureteral stents were placed using a retrograde or antegrade approach. Therapeutic effects and complications were recorded. The Wilcoxon signed-rank test was used to compare continuous variables between the preoperative and the last follow-up. A total of 25 patients (27 sides) were included in this study. After a follow-up time of 18 (11-29) months, the width of hydronephrosis [1.6 (1.0-2.2) cm vs 2.6 (1.2-3.3) cm, P = .000], glomerular filtration rate [83.8 (58.1-86.4) mL/minutes/1.73 m2 vs 74.5 (56.8-79.1) mL/minutes/1.73 m2, P = .001] and score of ureteral stent symptoms questionnaire [77 (76-79) vs 100 (98-103), P = .000] was significantly improved. Stent migration occurred in 3 of the 25 patients within 3 months after surgery. All patients with complications were followed up for at least 6 months after stent adjustment or exchange, and no other complications were found. Two patients died because of malignant complications. The stent patency rate was 88.9% (24/27) after the first operation, and 100% (27/27) after complications were treated. The Allium ureteral stent is safe and effective for the maintenance therapy of MUO, which can dramatically relieve the symptoms of patients. Stent migration is a major complication that can be resolved by endoscopic adjustment.

Stabilizing Co2C with H2O and K promoter for CO2 hydrogenation to C2+ hydrocarbons.

The decomposition of cobalt carbide (Co2C) to metallic cobalt in CO2 hydrogenation results in a notable drop in the selectivity of valued C2+ products, and the stabilization of Co2C remains a grand challenge. Here, we report an in situ synthesized K-Co2C catalyst, and the selectivity of C2+ hydrocarbons in CO2 hydrogenation achieves 67.3% at 300°C, 3.0 MPa. Experimental and theoretical results elucidate that CoO transforms to Co2C in the reaction, while the stabilization of Co2C is dependent on the reaction atmosphere and the K promoter. During the carburization, the K promoter and H2O jointly assist in the formation of surface C* species via the carboxylate intermediate, while the adsorption of C* on CoO is enhanced by the K promoter. The lifetime of the K-Co2C is further prolonged from 35 hours to over 200 hours by co-feeding H2O. This work provides a fundamental understanding toward the role of H2O in Co2C chemistry, as well as the potential of extending its application in other reactions.

Long-term maintenance treatment of recurrent ureteropelvic junction obstruction with covered metallic ureteral stent.

Whether or not the covered metallic ureteral stent can be used as maintenance treatment for recurrent ureteropelvic junction obstruction (UPJO) after pyeloplasty is unknown. Therefore, this study aims to analyze its feasibility. We retrospectively analyzed the records of 20 patients with recurrent UPJO who were treated with the covered metallic ureteral stents from March 2019 to June 2021 at our institution. Then, we assessed their renal function, stent patency and stent-related quality of life by the blood creatinine, renal ultrasound (or computed tomography), and the Chinese version of the ureteral symptom score questionnaire (USSQ). The last follow-up mean blood creatinine dropped from 0.98 ± 0.22 to 0.91 ± 0.21 mg/dL (P = .04), and the median renal pelvic width was reduced from 3.25 (3.10) to 2.00 (1.67) cm (P = .03) compared with the preoperative conditions. Meanwhile, the last follow-up mean USSQ total score of the covered metallic ureteral stent among the 16 patients with preoperative indwelling double-J ureteral stent was 78.56 ± 14.75, significantly lower than the preoperative USSQ total score, which was 102.25 ± 5.57 (P < .001). During the median duration of follow-up of 27.00 (18.00) months, 85% (17/20) of patients maintained unobstructed drainage from the renal pelvis to the ureter. Stent-related complications occurred in 7 patients, 3 of which failed because of complications, including stent migration (1 patient), stent encrustation (1 patient), and stent-related infection (1 patient). The covered metallic ureteral stent is feasible for the long-term maintenance treatment of recurrent UPJO after pyeloplasty.

The collective effects of genetic variants and complex traits.

Traditional approaches in studying the genetics of complex traits have focused on identifying specific genetic variants. However, the collective effects of variants have remained largely unexplored. Here, we evaluated whether traits could be influenced by the collective effects of variants across the entire protein coding-region of the genome or the entire genome. We studied the UK Biobank exome sequencing data of 167,246 individuals as well as the genome-wide SNP array data of 408,868 individuals. We calculated for each individual four different measures of genetic variation such as heterozygosity and number of variants and two different measures of the overall deleteriousness of all variants, and performed correlations with 17 representative traits that have been studied previously. Linear regression analysis was performed with adjustment for age, sex, and genetic principal components. The results showed a high correlation among the six different measures and an inverse association of two well-correlated traits (educational attainment and height) with the total number of all variants as well as the overall deleteriousness of all variants. We have also categorized the genes based on whether they are expressed in the brain and found that the association with educational attainment only held for the brain-expressed genes. No other traits examined showed a significant correlation with the brain-expressed genes. The study demonstrates that common traits could be studied by analyzing the overall genetic variation and suggests that educational attainment is inversely related to genetic variation.

Interleukin-37 suppresses the cytotoxicity of hepatitis B virus peptides-induced CD8+ T cells in patients with acute hepatitis B.

Interleukin-37 (IL-37) is a newly identified anti-inflammatory cytokine, owning immunosuppressive activity in infectious diseases. The aim of this study was to investigate the regulatory function of IL-37 on CD8+ T cells during hepatitis B virus (HBV) infection. Eighteen acute hepatitis B (AHB) patients, thirty-nine chronic hepatitis B (CHB) patients, and twenty controls were enrolled. IL-37 concentration was measured by ELISA. IL-37 receptor subunits expressions on CD8+ T cells were assessed by flow cytometry. Purified CD8+ T cells were stimulated with HBV peptides and recombinant IL-37. Perforin and granzyme B secretion was investigated by ELISPOT. Programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) mRNA expressions were semi-quantified by real-time PCR. CD8+ T cell cytotoxicity was assessed in direct contact and indirect contact coculture with HepG2.2.15 cells. Plasma IL-37 level was down-regulated and negatively correlated with aminotransferase levels in AHB patients. There were no significant differences of IL-37 receptor subunits among AHB patients, CHB patients, and controls. Exogenous IL-37 stimulation suppressed HBV peptides-induced perforin and granzyme B secretion by CD8+ T cells in AHB patients, but not in CHB patients. Exogenous IL-37 stimulation did not affect proinflammatory cytokines secretion as well as PD-1/CTLA-4 mRNA expressions in CD8+ T cells in AHB and CHB patients. Exogenous IL-37 stimulation dampened HBV peptide-induced CD8+ T cell cytotoxicity in a cell-to-cell contact manner. The current data indicated that acute HBV infection might induce down-regulation of IL-37, which might be associated with enhanced CD8+ T cell cytotoxicity and liver damage.

Study on the Manipulation Strategy of Metallic Microstructures Based on Electrochemical-Assisted Method.

Microcomponent manipulation (MCM) technology plays a decisive role in assembling complex systems at the micro- and nanoscale. However, the existing micromanipulation methods are difficult to widely apply in the manufacturing of microelectromechanical systems (MEMSs) due to the limited manipulation space and complex application objects, and the manipulation efficiency is relatively low, which makes it difficult to industrialize these micromanipulating systems. To solve the above problems, this paper proposes an efficient metal MCM strategy based on the electrochemical method. To verify the feasibility and repeatability of the strategy, the finite element model (FEM) incorporating the hydrodynamic and electrochemical theories is used to calculate the local stress distribution of the contact position during the dynamic pick-up process. Based on the simulation results, we defined the relationship between the parameters, such as the optimal manipulating position and angle for picking, transferring and releasing. The failure behaviors of pick-up are built to realize the efficient three-dimensional manipulation of microcopper wire of 300 µm. By establishing a theoretical model and experimental verification, it was concluded that the middle point was the best manipulating position when picking up the microcopper wire, the most efficient picking angle was between 45 and 60 degrees for the pipette, and the average time was 480 s in three sets of picking-release manipulation experiments. This paper provides an achievable idea for different types of micro-object manipulations and promotes the rapid application of micromanipulation techniques in MEMSs.

Breathable and Waterproof Electronic Skin with Three-Dimensional Architecture for Pressure and Strain Sensing in Nonoverlapping Mode.

Wearable sensors have recently attracted extensive interest not only in the field of healthcare monitoring but also for convenient and intelligent human-machine interactions. However, challenges such as wearable comfort, multiple applicable conditions, and differentiation of mechanical stimuli are yet to be fully addressed. Herein, we developed a breathable and waterproof electronic skin (E-skin) that can perceive pressure/strain with nonoverlapping signals. The synergistic effect from magnetic attraction and nanoscaled aggregation renders the E-skin with microscaled pores for breathability and three-dimensional microcilia for superhydrophobicity. Upon applied pressure, the bending of conductive microcilia enables sufficient contacts for resistance decrease, while the stretching causes increased resistance due to the separation of conductive materials. The optimized E-skin exhibits a high gauge factor of 7.747 for small strain (0-80%) and a detection limit down to 0.04%. The three-dimensional microcilia also exhibit a sensitivity of -0.0198 kPa-1 (0-3 kPa) and a broad detection range up to 200 kPa with robustness. The E-skin can reliably and precisely distinguish kinds of the human joint motions, covering a broad spectrum including bending, stretching, and pressure. With the nonoverlapping readouts, ternary inputs "1", "0", and "-1" could be produced with different stimuli, which expands the command capacity for logic outputs such as effective Morse code and intuitive robotic control. Owing to the rapid response, long-term stability (10 000 cycles), breathability, and superhydrophobicity, we believe that the E-skin can be widely applied as wearable devices from body motion monitoring to human-machine interactions toward a more convenient and intelligent future.

Defect-Guided Synthesis of Hierarchical Sn-B-Beta Zeolite with Highly Exposed Sn Sites.

Selectively anchoring active centers on the external surface for forming highly exposed acid sites is a highly desirable but challenging task in zeolite catalyst synthesis. Herein, a defect-guided etching-regrowth strategy is rationally designed for facilely positioning Sn Lewis acid sites on the outer surface of the Sn-B-Beta while fabricating a bifunctional hierarchical structure. The synthesis was conducted by hydrothermal treatment of the as-made B-Beta (uncalcined), which has intrinsic defects of the BEA structure, with Sn source and basic organic structure directing agent (SDA). Under a moderate SDA concentration, with blocked micropore channels, such SDA-triggered etching-regrowth will proceed along the defect defined pathway, which ensures Sn selectively anchored on the external surface. Moreover, this methodology has exclusively introduced tetrahedrally coordinated framework Sn with open Sn sites as the predominated species. Mono- and disaccharide isomerizations in ethanol over different Sn-Beta catalysts proved the prominent advantages of the hierarchical structure with highly exposed and synergetic acid sites.

A Self-Sustained System Spanning the Primary and Secondary Metabolism Stages to Boost the Productivity of Streptomyces.

Streptomyces species possess strong secondary metabolism, the switches of which from the primary metabolism are complex and thus a challenge to holistically optimize their productivities. To avoid the complex switches and to reduce the limitations of different metabolic stages on the synthesis of metabolites, we designed a Streptomyces self-sustained system (StSS) that contains two functional modules, the primary metabolism module (PM) and the secondary metabolism module (SM). The PM includes endogenous housekeeping sigma factor σhrdB and σhrdB-dependent promoters, which are used to express target genes in the primary metabolism phase. SM consists of the expression cassette of σhrdB under the control of a secondary metabolism promoter, which maintains continuous activity of the σhrdB-dependent promoters in the secondary metabolism phase. As a proof-of-principle, the StSS was used to boost the production of some non-toxic metabolites, including indigoidine, undecylprodigiosin (UDP), ergothioneine, and avermectin, in Streptomyces. All these metabolites can undergo a continuous production process spanning the primary and secondary metabolism stages instead of being limited to a specific stage. Scale-up of UDP fermentation in a 4 L fermentor indicated that the StSS is a stable and robust system, the titer of which was enhanced to 1.1 g/L, the highest at present. This study demonstrated that the StSS is a simple but powerful strategy to rationally engineer Streptomyces cell factories for the efficient production of non-toxic metabolites via reconstructing the relationships between primary and secondary metabolism.

Extracellular vesicles in acute respiratory distress syndrome: Recent developments from bench to bedside.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), characterized by a large number of inflammatory cell aggregation and alveolar cell damage in pathophysiology, have extremely high morbidity and mortality in critically ill patients. In recent years, more and more studies have found that there are abundant extracellular vesicles (EVs) in animal models and patients with ALI/ARDS, and they play a critical role in the pathogenesis of lung injury. Clarifying the mechanisms of EVs in lung injury is of great significance in the diagnosis and treatment of ALI/ARDS. In this review, we will summarize the recent findings on the roles of EVs derived from different cells in ALI/ARDS, along with the formation, function, and related effects of EVs, and explore their potential clinical application for the diagnosis and treatment of ALI/ARDS.