M6[Cd2(CO3)2(B12O18)(OH)6] (M = K, Rb): Borate-Carbonates with Two CdCO3 Embedded in a Cyclic Oxoboron Anion.

Two metal borate-carbonates, M6[Cd2(CO3)2(B12O18)(OH)6] [M = K (1), Rb (2)], were obtained under surfactant-thermal conditions. In 1 and 2, each cyclic [(B12O18)(OH)6]6- anion captures two CdCO3 in two sides of the rings and finally forms the unusual (CdCO3)2@[(B12O18)(OH)6] cluster. Both 1 and 2 show moderate birefringence. Density functional theory calculations indicate that carbonate groups have a major contribution to electron-related optical transition.

Contralateral C7 nerve transfer in the treatment of central hemiplegia after stroke under general anesthesia: A case report.

Similar reports in the past pay less attention to the anesthetic management of these patients. We reported a 46-year-old man who suffered from hypertensive cerebral apoplexy 5 months ago and accepted C7 nerve transfer to improve the central spastic paralysis in the right upper limb. After careful evaluation and anesthesia management before anesthesia, the operation was successfully completed under general anesthesia. The patient was cured and discharged without complications. The anesthesia management of C7 nerve transfer should choose appropriate operation opportunities for patients according to the type of stroke, improve the preoperative preparation, and form a multidisciplinary diagnosis and treatment.

A tale of two fusion proteins: understanding the metastability of human respiratory syncytial virus and metapneumovirus and implications for rational design of uncleaved prefusion-closed trimers.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we designed uncleaved prefusion-closed (UFC) trimers for the fusion (F) proteins of both viruses by examining mutations critical to F metastability. For RSV, we assessed four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identified key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we developed a stable UFC trimer with a truncated F2-F1 linkage and an interprotomer disulfide bond. Tens of UFC constructs were characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F and one hMPV-F structures), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identified three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induced robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development.

Restoration of the Mucosal IgA Response by Improving CD4+ T Pyroptosis Fails to Attenuate Gut Bacterial Translocation and Organ Damage After LPS Attack.

BACKGROUND: Currently, the mechanisms of impaired gut mucosal immunity in sepsis remain unclear. Gut immunoglobulin A (IgA) is an important defense mechanism against invasive pathogens, and CD4+ T cells regulate the IgA response. AIM: We aimed to verify the hypothesis indicating that CD4+ T pyroptosis induced by lipopolysaccharide (LPS) leads to an impaired gut IgA response and subsequent bacterial translocation and organ damage. METHODS: Cultured CD4+ T cells and mice were manipulated with LPS, and pyroptosis was improved by A438079 or adoptive CD4+ T cell transfer. The changes demonstrated in pyroptosis-related molecules, cytotoxicity and CD4+ T cells were examined to determine CD4+ T pyroptosis. The changes demonstrated in IgA+ B cells, AID (key enzyme for immunoglobulins) and IgA production and function were examined to evaluate the IgA response. Serum biomarkers, bacterial colonies and survival analysis were detected for bacterial translocation and organ damage. RESULTS: LPS attack induced CD4+ T pyroptosis, as evidenced by increased expression of P2X7, Caspase-11 and cleaved GSDMD, which elevated cytotoxicity and decreased CD4+ T cells. Decreased CD4+ T subsets (Foxp3+ T and Tfh cells) influenced the IgA response, as evidenced by lower AID expression, which decreased IgA+ B cells and IgA production and function. A438079 or cell transfer improved the IgA response but failed to reduce the translocation of gut pathogens, damage to the liver and kidney, and mortality of mice. CONCLUSION: LPS attack results in CD4+ T pyroptosis. Improvement of pyroptosis restores the mucosal IgA response but fails to ameliorate bacterial translocation and organ damage.

Single-Component Multilayered Self-Assembling Protein Nanoparticles Displaying Extracellular Domains of Matrix Protein 2 as a Pan-influenza A Vaccine.

The development of a cross-protective pan-influenza A vaccine remains a significant challenge. In this study, we designed and evaluated single-component self-assembling protein nanoparticles (SApNPs) presenting the conserved extracellular domain of matrix protein 2 (M2e) as vaccine candidates against influenza A viruses. The SApNP-based vaccine strategy was first validated for human M2e (hM2e) and then applied to tandem repeats of M2e from human, avian, and swine hosts (M2ex3). Vaccination with M2ex3 displayed on SApNPs demonstrated higher survival rates and less weight loss compared to the soluble M2ex3 antigen against the lethal challenges of H1N1 and H3N2 in mice. M2ex3 I3-01v9a SApNPs formulated with a squalene-based adjuvant were retained in the lymph node follicles over 8 weeks and induced long-lived germinal center reactions. Notably, a single low dose of M2ex3 I3-01v9a SApNP formulated with a potent adjuvant, either a Toll-like receptor 9 (TLR9) agonist or a stimulator of interferon genes (STING) agonist, conferred 90% protection against a lethal H1N1 challenge in mice. With the ability to induce robust and durable M2e-specific functional antibody and T cell responses, the M2ex3-presenting I3-01v9a SApNP provides a promising pan-influenza A vaccine candidate.

Prognosis of Older Adult Patients Suffering from Atrial Fibrillation and Hypokalemia.

Objective: To examine the effects of hypokalemia on the prognosis of older adult patients with atrial fibrillation (AF). Methods: We enrolled 794 older adult patients ≥ 75 years suffering from AF, and divided them into two groups according to the inclusion and exclusion criteria: Group 1, (hypokalemia group), 246 cases, serum K+<3.5 mmol/L; Group 2, (normal blood potassium group), 548 cases, 3.5mmol/L≤serum K+<5.5 mmol/L. The two groups of patients were followed for 70 months to observe the occurrence of clinical events. The primary endpoint was cardiovascular death and the secondary endpoint was all-cause death. Results: The median follow-up time was 15.00 months. In terms of baseline profile characteristics, serum creatinine levels were significantly lower in Group 1 than in Group 2 patients (P=0.002). In terms of the relationship between hypokalemia and clinical outcomes, Kaplan-Meier survival analysis revealed that the incidence of clinical primary endpoint in Group 1 was significantly higher than that in Group 2 (P < 0.001), and the incidence of the secondary endpoint did not differ significantly between the two groups (P> 005). Based on multivariate Cox regression risk model analysis, coronary heart disease, hemoglobin content, serum uric acid and usage of anticoagulant drugs were the independent variables related to the primary endpoint of cardiovascular death (all P< 0.01). Conclusion: The incidence of hypokalemia in older adult patients with AF was 30.98%. Hypokalemia was closely related to the cardiovascular death, and coronary heart disease, hemoglobin content, serum uric acid level, and usage of anticoagulant drugs were the independent risk factors for the primary endpoint event.

MLink: Linking Black-Box Models From Multiple Domains for Collaborative Inference.

The cost efficiency of model inference is critical to real-world machine learning (ML) applications, especially for delay-sensitive tasks and resource-limited devices. A typical dilemma is: in order to provide complex intelligent services (e.g., smart city), we need inference results of multiple ML models, but the cost budget (e.g., GPU memory) is not enough to run all of them. In this work, we study underlying relationships among black-box ML models and propose a novel learning task: model linking, which aims to bridge the knowledge of different black-box models by learning mappings (dubbed model links) between their output spaces. We propose the design of model links which supports linking heterogeneous black-box ML models. Also, in order to address the distribution discrepancy challenge, we present adaptation and aggregation methods of model links. Based on our proposed model links, we developed a scheduling algorithm, named MLink. Through collaborative multi-model inference enabled by model links, MLink can improve the accuracy of obtained inference results under the cost budget. We evaluated MLink on a multi-modal dataset with seven different ML models and two real-world video analytics systems with six ML models and 3,264 hours of video. Experimental results show that our proposed model links can be effectively built among various black-box models. Under the budget of GPU memory, MLink can save 66.7% inference computations while preserving 94% inference accuracy, which outperforms multi-task learning, deep reinforcement learning-based scheduler and frame filtering baselines.

Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.

Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 native-like Env trimers as vaccine candidates. We characterize the biophysical, structural, and antigenic properties of 1c-SApNPs that present the BG505 UFO trimer with wildtype and modified glycans. For 1c-SApNPs, glycan trimming improves recognition of the CD4 binding site without affecting broadly neutralizing antibodies (bNAbs) to major glycan epitopes. In mice, rabbits, and nonhuman primates, glycan trimming increases the frequency of vaccine responders (FVR) and steers antibody responses away from immunodominant glycan holes and glycan patches. The mechanism of vaccine-induced immunity is examined in mice. Compared with the UFO trimer, the multilayered E2p and I3-01v9 1c-SApNPs show 420 times longer retention in lymph node follicles, 20-32 times greater presentation on follicular dendritic cell dendrites, and up-to-4 times stronger germinal center reactions. These findings can inform future HIV-1 vaccine development.

The Effect of Self-Stigma on the Hope of Chinese with Mental Illness: The Mediating Role of Family Function.

Objective: This cross-sectional study examined the levels of self-stigma, hope, and family functioning among Chinese people with mental illness (MI). We also investigated the mediating role of family functioning in the relationship between self-stigma and hope. Method: Three-hundred thirty participants with MI (Mage = 42.73, SD = 14.11, 52.09% female, 61.74% schizophrenia) were surveyed. Hayes' PROCESS macro analysis (Model 4) was performed to verify the mediating effect. Results: The analysis revealed that 43.1% of the respondents had a high level of self-stigma, 68.5% indicated a low/moderate level of hope, and 54% had moderate/severe impairment in family functioning. This supports the partial mediating effect of family functioning on the relationship between self-stigma and hope. Conclusions: The self-stigmatizing experiences of Chinese people with MI adversely impair normal family functioning and reduce hope, limiting recovery prospects. Relevant results highlight the influence of the family environment on the psychological mechanisms of PMI. Limitations and future research directions are addressed.

[Effects of resveratrol on inhibiting pyroptosis of intestinal cancer cells].

Objective: To study the effects of resveratrol (Res) on pyroptosis of colorectal cancer cells . Methods: ①The experiment of dextran sodium sulfate (DSS) induced colon cancer (CRC) in mice: 30 C57BL/6 mice were randomly divided into control group, Azoxymethane (AOM) group, AOM/DSS group, AOM/DSS+Res group and Res group, with 6 mice in each group, the modeling cycle was 70 days in total. Mice in AOM group, AOM/DSS group and AOM/DSS+Res group, at the first day of the first week, were intraperitoneally injected with AOM (10 mg/kg) once, and the ordinary chaw was replaced with high iron feed, and sterile water was given, 1% DSS water was given to AOM/DSS group and AOM/DSS+Res group. The mice in AOM/DSS+Res and Res groups were given resveratrol (50 mg/kg) by oral gavage, When the mold was finished, colon tissue of mice was fixed, embedded and sectionalized. The expressions of NLRP3, Caspase-1 and IL-18 in colon tissues of mice were detected by IHC and Western blot. ②In vitro experiment: HCT 116 cells were given Res (2.4 µg/L) and transfected with miR-31. The Res was divided into 4 groups and labeled with 0 h, 12 h, 24 h and 48 h respectively. The transfected cells were divided into 5 groups: Control group, miR-31 mimic group, miR-31 mimic + Res group, miR-31 inhibitor group, miR-31 inhibitor + Res group. The protein expressions of NLRP3, Caspase-1, GSDMD-N, IL-18 and IL-1ß were detected by Western blot. Results: Animal experiments: Compared with control group, the protein expressions of NLRP3, Caspase-1 and IL-18 in AOM/DSS group were increased significantly (P<0.01). The protein expression levels of NLRP3, Caspase-1 and IL-18 in AOM/DSS+Res group were significantly lower than those in AOM/DSS group (P<0.01). Cell experiments: Compared with the control group, the protein expressions of NLRP3 (P<0.01), GSDMD-N (P<0.05) and IL-18 (P< 0.01) in miR-31 mimic group were increased significantly. The protein expressions of NLRP3, GSDMD-N and IL-18 in miR-31 inhibitor group were decreased significantly (P<0.05). Conclusion: Res inhibited the pyroptosis of colorectal cancer cells through pyroptosis.

Quantitative PCR Assays for the Strain-Specific Identification and Enumeration of Probiotic Strain Lacticaseibacillus rhamnosus X253.

Probiotics are universally recognized for their health benefits, despite the fact that their effects depend on the strain. Identification and enumeration of probiotic strains are required prior to evaluating their effectiveness. Lacticaseibacillus rhamnosus X253 is a potential probiotic strain with antioxidant capacity. Comparative genomics and single nucleotide polymorphisms (SNPs) were used to identify a strain-specific locus within the holA gene for strain X253 that was distinct in 30 different L. rhamnosus strains. Using quantitative PCR, the primers and probe designed for the locus were able to distinguish L. rhamnosus X253 from the other 20 probiotic strains. The chosen locus remained stable over 19 generations. The sensitivity of the assay was 0.2 pg genomic DNA of L. rhamnosus X253, or 103 cfu/mL bacteria of this strain. In terms of repeatability and reproducibility, relative standard deviations (RSD) were less than 1% and 3%, respectively. Additionally, this assay achieved accurate enumerations of L. rhamnosus X253 in spiked milk and complex powder samples. The strain-specific assay could be used for quality control and compliance assessment of dairy products.

The association between dose of hemodialysis and patients mortality in a prospective cohort study.

Dialysis adequacy is a known risk factor for mortality in maintenance hemodialysis (MHD) patients. However, the optimal dialysis dose remains controversial. Therefore, we aimed to explore the relationship between dialysis dose and all-cause and cardiovascular disease (CVD) mortality among MHD. We examined the associations of dialysis dose with mortality in a cohort (n = 558) of MHD patients from 31 December 2015 to 31 December 2020. Dialysis adequacy was assessed using baseline Single-pool Kt/Vurea (spKt/V), which was categorized into three groups, and the lowest dose group was used as the reference category. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 214 patients died (64.5% for CVD). Compared with the low-dose group, high-dose group could reduce the risk of all-cause mortality by 33% (HR = 0.67, 95% CI: 0.47-0.98). Of note, when stratification by age, high-dose group was associated with both lower all-cause (HR = 0.46, 95% CI: 0.26-0.81) and CVD mortality (HR = 0.42, 95% CI: 0.20-0.88) among patients with age below 65 years. When stratification by dialysis age, high-dose group was associated with decreased risk of CVD mortality (HR = 0.43, 95% CI: 0.20-0.91) among patients with dialysis age over 60 months. spKt/V is a simple index of hemodialysis dose used in clinical practice and a useful modifiable factor in predicting the risk of death, especially in MHD patients under 65 years old or dialysis age more than 60 months.

Complex Flavanones from Cryptocarya metcalfiana and Structural Revision of Oboflavanone A.

Nine new complex flavanones, cryptometcones A-I (1-9), along with four known analogues, were isolated from Cryptocarya metcalfiana. The structures of 1-9 including their absolute configurations were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. In addition, the structure of oboflavanone A was revised, while the absolute configurations of oboflavanone B, cryptoflavanone C, and cryptoflavanone D were determined, according to their spectroscopic data. Compounds 3-5, 8, and 9 exhibited cytotoxicity against the HCT-116 cancer cell line.

Impact of Tumor Barriers on Nanoparticle Delivery to Macrophages.

The delivery of therapeutic nanoparticles to target cells is critical to their effectiveness. Here we quantified the impact of biological barriers on the delivery of nanoparticles to macrophages in two different tissues. We compared the delivery of gold nanoparticles to macrophages in the liver versus those in the tumor. We found that nanoparticle delivery to macrophages in the tumor was 75% less than to macrophages in the liver due to structural barriers. The tumor-associated macrophages took up more nanoparticles than Kupffer cells in the absence of barriers. Our results highlight the impact of biological barriers on nanoparticle delivery to cellular targets.

FX5, a non-steroidal glucocorticoid receptor antagonist, ameliorates diabetic cognitive impairment in mice.

Diabetic cognitive impairment (DCI) is a common diabetic complication characterized by learning and memory deficits. In diabetic patients, hyperactivated hypothalamic-pituitary-adrenal (HPA) axis leads to abnormal increase of glucocorticoids (GCs), which causes the damage of hippocampal neurons and cognitive impairment. In this study we investigated the cognition-improving effects of a non-steroidal glucocorticoid receptor (GR) antagonist 5-chloro-N-[4-chloro-3-(trifluoromethyl) phenyl]thiophene-2-sulfonamide (FX5) in diabetic mice. Four weeks after T1DM or T2DM was induced, the mice were administered FX5 (20, 40 mg·kg-1·d-1, i.g.) for 8 weeks. Cognitive impairment was assessed in open field test, novel object recognition test, Y-maze test, and Morris water maze test. We showed that FX5 administration significantly ameliorated the cognitive impairments in both type 1 and 2 diabetic mice. Similar cognitive improvement was observed in diabetic mice following brain GR-specific knockdown by injecting AAV-si-GR. Moreover, AAV-si-GR injection occluded the cognition-improving effects of FX5, suggesting that FX5 functioning as a non-steroidal GR antagonist. In PA-treated primary neurons (as DCI model in vitro), we demonstrated that FX5 (2, 5, 10 µM) dose-dependently ameliorated synaptic impairment via upregulating GR/BDNF/TrkB/CREB pathway, protected against neuronal apoptosis through repressing GR/PI3K/AKT/GSK3ß-mediated tauopathy and subsequent endoplasmic reticulum stress. In LPS-treated primary microglia, FX5 dose-dependently inhibited inflammation through GR/NF-κB/NLRP3/ASC/Caspase-1 pathway. These beneficial effects were also observed in the hippocampus of diabetic mice following FX5 administration. Collectively, we have elucidated the mechanisms underlying the beneficial effects of non-steroidal GR antagonist FX5 on DCI and highlighted the potential of FX5 in the treatment of the disease.

Ba2B10O16(OH)2·(H3BO3)(H2O): A Possible Deep-Ultraviolet Nonlinear-Optical Barium Borate.

A new acentric barium borate, Ba2B10O16(OH)2·(H3BO3)(H2O) (1), was synthesized via a hydrothermal process. Compound 1 contains two different boron oxide units of [B5O10(OH)]6- anions and H3BO3 molecules and features 9-ring channels along the c axis in a layered structure. This barium borate is a possible deep-ultraviolet nonlinear-optical crystal for its moderate second-harmonic-generation signal and wide transparency window below 190 nm.

Sacrificial Co-solvent Electrolyte to Construct a Stable Solid Electrolyte Interphase in Lithium-Oxygen Batteries.

Lithium-oxygen batteries are vital devices for electrochemical energy storage. The electrolyte is a crucial factor for improving battery performance. The high reactivity of lithium metal induces side reactions with organic electrolytes, thus leading to an unstable interface between the anode and electrolyte and poor performance of batteries. In this work, to compensate for the above shortcomings, 1-methylimidazole (MeIm) is introduced to the tetraethylene glycol dimethyl ether (TEGDME) electrolyte to form the TEGDME/MeIm co-solvent electrolyte. Because of the high donor number value of MeIm, the solution-based pathway of discharge products can be triggered. Compared with the single TEGDME electrolyte, the discharge capacity with the TEGDME/MeIm co-solvent electrolyte is increased by more than 2 times. Moreover, the TEGDME/MeIm co-solvent electrolyte can promote the dissociation of Li salt due to the high dielectric constant of MeIm and thus make up for the shortcomings of TEGDME. In addition, due to the lower energy than the lowest unoccupied molecular orbital (LUMO) level of TEGDME, MeIm is decomposed preferentially, and a dense solid electrolyte interphase (SEI) layer is constructed. Then, the decomposition of TEGDME is suppressed. Therefore, the cycle performance of the battery with the TEGDME/MeIm co-solvent electrolyte is 18 times compared to that with the single TEGDME electrolyte.

Research advances in the clinical application of esketamine.

Esketamine is dextrorotatory ketamine, which is an enantiomer of ketamine. Compared with ketamine, it has the advantages of a fast metabolism, fewer side effects, and strong pharmacological effects, so it is more suitable for clinical use. Esketamine has a powerful analgesic effect and has little effect on breathing. It has a wide range of applications in the fields of pediatric anesthesia, conscious sedation anesthesia, and emergency analgesia. In addition, it is also used for pain that is difficult to relieve with conventional drugs and to prevent postoperative pain. Various routes of administration are also suitable for patients who need short-term analgesia and sedation. As a drug, esketamine inevitably brings some side effects when it is used clinically. In this article, by introducing the mechanism of action and pharmacological characteristics of esketamine, its clinical application is reviewed, and it provides a reference for the more reasonable and safe clinical application of esketamine.

Dexmedetomidine Alleviates Gut-Vascular Barrier Damage and Distant Hepatic Injury Following Intestinal Ischemia/Reperfusion Injury in Mice.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) challenge often results in gut barrier dysfunction and induces distant organ injury. Dexmedetomidine has been shown to protect intestinal epithelial barrier against I/R attack. The present study aims to investigate the degree to which intestinal I/R attack will contribute to gut-vascular barrier (GVB) damage, and to examine the ability of dexmedetomidine to minimize GVB and liver injuries in mice. METHODS: In vivo, intestinal ischemic challenge was induced in mice by clamping the superior mesenteric artery for 45 minutes. After clamping, the mice were subjected to reperfusion for either 2, 4, 6, or 12 hours. Intraperitoneal injection of dexmedetomidine 15, 20, or 25 µg·kg-1 was performed intermittently at the phase of reperfusion. For the in vitro experiments, the challenge of oxygen-glucose deprivation/reoxygenation (OGD/R) was established in cultured vascular endothelial cells, and dexmedetomidine (1 nM) was used to treat the cells for 24 hours. Moreover, in vivo and in vitro, SKL2001 (a specific agonist of ß-catenin) or XAV939 (a specific inhibitor of ß-catenin) was applied to determine the role of ß-catenin in the impacts provided by dexmedetomidine. RESULTS: The attack of intestinal I/R induced GVB damage. The greatest level of damage was observed at 4 hours after intestinal reperfusion. There was a significant increase in plasmalemma vesicle-associated protein-1 (PV1, a specific biomarker for endothelial permeability) expression (5.477 ± 0.718 vs 1.000 ± 0.149; P < .001), and increased translocation of intestinal macromolecules and bacteria to blood and liver tissues was detected (all P < .001). Liver damages were observed. There were significant increases in histopathological scores, serum parameters, and inflammatory factors (all P < .001). Dexmedetomidine 20 µg·kg-1 reduced PV1 expression (0.466 ± 0.072 vs 1.000 ± 0.098; P < .001) and subsequent liver damages (all P < .01). In vitro, dexmedetomidine significantly improved vascular endothelial cell survival (79.387 ± 6.447% vs 50.535 ± 1.766%; P < .001) and increased the productions of tight junction protein and adherent junction protein (all P < .01) following OGD/R. Importantly, in cultured cells and in mice, ß-catenin expression significantly decreased (both P < .001) following challenge. Dexmedetomidine or SKL2001 upregulated ß-catenin expression and produced protective effects (all P < .01). However, XAV939 completely eliminated the protective effects of dexmedetomidine on GVB (all P < .001). CONCLUSIONS: The disruption of GVB occurred following intestinal I/R. Dexmedetomidine alleviated I/R-induced GVB impairment and subsequent liver damage.