Risk factors for postoperative pulmonary complications in elderly patients undergoing video-assisted thoracoscopic surgery lobectomy under general anesthesia: a retrospective study.

BACKGROUND: The objective of this study is to identify and evaluate the risk factors associated with the development of postoperative pulmonary complications (PPCs) in elderly patients undergoing video-assisted thoracoscopic surgery lobectomy under general anesthesia. METHODS: The retrospective study consecutively included elderly patients (≥ 70 years old) who underwent thoracoscopic lobectomy at Xuanwu Hospital of Capital Medical University from January 1, 2018 to August 31, 2023. The demographic characteristics, the preoperative, intraoperative and postoperative parameters were collected and analyzed using multivariate logistic regression to identify the prediction of risk factors for PPCs. RESULTS: 322 patients were included for analysis, and 115 patients (35.7%) developed PPCs. Multifactorial regression analysis showed that ASA ≥ III (P = 0.006, 95% CI: 1.230 ∼ 3.532), duration of one-lung ventilation (P = 0.033, 95% CI: 1.069 ∼ 4.867), smoking (P = 0.027, 95% CI: 1.072 ∼ 3.194) and COPD (P = 0.015, 95% CI: 1.332 ∼ 13.716) are independent risk factors for PPCs after thoracoscopic lobectomy in elderly patients. CONCLUSION: Risk factors for PPCs are ASA ≥ III, duration of one-lung ventilation, smoking and COPD in elderly patients over 70 years old undergoing thoracoscopic lobectomy. It is necessary to pay special attention to these patients to help optimize the allocation of resources and enhance preventive efforts.

Organic Solvent Boosts Charge Storage and Charging Dynamics of Conductive MOF Supercapacitors.

Conductive metal-organic frameworks (c-MOFs) and ionic liquids (ILs) have emerged as auspicious combinations for high-performance supercapacitors. However, the nanoconfinement from c-MOFs and high viscosity of ILs slow down the charging process. This hindrance can, however, be resolved by adding solvent. Here, constant-potential molecular simulations are performed to scrutinize the solvent impact on charge storage and charging dynamics of MOF-IL-based supercapacitors. Conditions for >100% enhancement in capacity and ≈6 times increase in charging speed are found. These improvements are confirmed by synthesizing near-ideal c-MOFs and developing multiscale models linking molecular simulations to electrochemical measurements. Fundamentally, the findings elucidate that the solvent acts as an "ionophobic agent" to induce a substantial enhancement in charge storage, and as an "ion traffic police" to eliminate convoluted counterion and co-ion motion paths and create two distinct ion transport highways to accelerate charging dynamics. This work paves the way for the optimal design of MOF supercapacitors.

A randomized, double-blind, placebo-controlled phase I clinical trial of rotavirus inactivated vaccine (Vero cell) in a healthy adult population aged 18-49 years to assess safety and preliminary observation of immunogenicity.

We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).

The Effectiveness of Target Temperature Management on Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the clinical efficacy of TTM in patients with poor-grade aSAH, we conducted a systematic review and meta-analysis. This research was registered in PROSPERO (CRD42023445582) and included all relevant publications up until October 2023. We compared the TTM groups with the control groups in terms of unfavorable outcomes (modified Rankin scale [mRS] score > 3), mortality, delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), and specific complications. Subgroup analyses were performed based on country, study type, follow-up time, TTM method, cooling maintenance period, and rewarming rate. Effect sizes were calculated as relative risk (RR) using random-effect or fixed-effect models. The quality of the articles was assessed using the methodological index for non-randomized studies scale. Our analysis included a total of 5 clinical studies (including 1 randomized controlled trial) and 219 patients (85 in the TTM group and 134 in the control group). Most of the studies were of moderate quality. TTM was found to be associated with a statistically significant improvement in mortality (mRS score 6) rates compared with the control group (RR = 0.61, 95% confidence interval [CI]: 0.40-0.94, p = 0.026). However, there was no statistically significant difference in unfavorable outcomes (mRS 4-6) between the TTM and control groups (RR = 0.94, 95% CI: 0.71-1.26, p = 0.702). The incidence of adverse events, including DCI, CVS, pneumonia, cardiac complications, and electrolyte imbalance, did not significantly differ between the two groups. In conclusion, our overall results suggest that TTM does not significantly reduce unfavorable outcomes in poor-grade aSAH patients. However, TTM may decrease mortality rates. Preoperative TTM may cause patients to miss the opportunity for surgery, although it temporarily protects the brain. Furthermore, the incidence of adverse events was similar between the TTM and control groups.

Effects of an early intensive blood pressure-lowering strategy using remifentanil and dexmedetomidine in patients with spontaneous intracerebral hemorrhage: a multicenter, prospective, superiority, randomized controlled trial.

BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and anti-sympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) ≥150 mmHg were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (<140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101/161, 62.7% vs. 66/166, 39.8%, difference 23.2%, 95% CI, 12.4 to 34.1%, P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP ≥ 150 mmHg, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management. (ClinicalTrials.gov number: NCT03207100, Registration date: June 30, 2017).

K33 only mutant ubiquitin augments bone marrow-derived dendritic cell-mediated CTL priming via PI3K-Akt pathway.

To explore the effect of K33 only mutant ubiquitin (K33O) on bone marrow-derived dendritic cells' (BMDCs') maturity, antigen uptake capability, surface molecule expressions and BMDC-mediated CTL priming, and further investigate the role of PI3K-Akt engaged in K33O-increased BMDC maturation, antigen uptake and presentation, surface molecule expressions and BMDC-based CTL priming. BMDCs were conferred K33O and other ubiquitin mutants (K33R, K48R, K63R-mutant ubiquitin) incubation or LY294002 and wortmannin pretreatment. PI3K-Akt phosphorylation, antigen uptake, antigenic presentation and CD86/MHC class I expression in BMDC were determined by western blot or flow cytometry. BMDC-based CTL proliferation and priming were determined by in vitro mixed lymphocyte reaction (MLR), ex vivo enzyme-linked immunospot assay (Elispot) and flow cytometry with intracellular staining, respectively. The treatment with K33O effectively augmented PI3K-Akt phosphorylation, BMDCs' antigen uptake, antigenic presentation, CD86/MHC class I and CD11c expressions. MLR, Elispot and flow cytometry revealed that K33O treatment obviously enhanced CTL proliferation, CTL priming and perforin/granzyme B expression. The pretreatment with PI3K-Akt inhibitors efficiently abrogated K33O's effects on BMDC. The replenishment of K33 only mutant ubiquitin augments BMDC-mediated CTL priming in bone marrow-derived dendritic cells via PI3K-Akt signalling.

Efficacy and Safety of High-Voltage Pulsed Radiofrequency versus Standard-Voltage Pulsed Radiofrequency for Patients with Neuropathic Pain: A Literature Review and Meta-Analysis.

Background: Neuropathic pain (NP) is recognized as one of the most difficult pain syndromes which lacks a safe, well-tolerated and effective treatment. Pulsed radiofrequency (PRF), a novel and minimally invasive interventions, has been introduced to alleviate various types of NP. Previous studies reported PRF with higher voltage could further improve the treatment efficacy. Therefore, we conducted this systematic review and meta-analysis to determine whether high-voltage PRF is superior to standard-voltage PRF for the treatment of NP patients. Methods: Databases published from the date of inception until 15 March 2022 on PubMed/MEDLINE, EMBASE, Web of Science and the Cochrane Library were searched for RCTs comparing high-voltage PRF and standard-voltage PRF in NP patients. The primary outcome measures were the efficiency rates of NP patients with high-voltage PRF or standard-voltage PRF treatment. Data analysis was conducted using the Review Manager software (RevMan V.5.3). Results: Six RCTs involving 423 patients were included in our meta-analysis. Compared with standard-voltage PRF group, the high-voltage PRF group attained a higher efficiency rate at 1 month (P = 0.04; I2 = 0%), 3 months (P = 0.04; I2 = 0%), 6 months (P = 0.002; I2 = 0%) post-procedure respectively. There was no significant difference in the complications between the two groups. Conclusion: Our study supported that high-voltage PRF attained more satisfactory efficacy than standard-voltage PRF without increased side effects. High-voltage PRF could be a promising, effective, minimally invasive technology for NP patients.

[Research on mode adjustment control strategy of upper limb rehabilitation robot based on fuzzy recognition of interaction force].

In the process of robot-assisted training for upper limb rehabilitation, a passive training strategy is usually used for stroke patients with flaccid paralysis. In order to stimulate the patient's active rehabilitation willingness, the rehabilitation therapist will use the robot-assisted training strategy for patients who gradually have the ability to generate active force. This study proposed a motor function assessment technology for human upper-limb based on fuzzy recognition on interaction force and human-robot interaction control strategy based on assistance-as-needed. A passive training mode based on the calculated torque controller and an assisted training mode combined with the potential energy field were designed, and then the interactive force information collected by the three-dimensional force sensor during the training process was imported into the fuzzy inference system, the degree of active participation σ was proposed, and the corresponding assisted strategy algorithms were designed to realize the adaptive adjustment of the two modes. The significant correlation between the degree of active participation σ and the surface electromyography signals (sEMG) was found through the experiments, and the method had a shorter response time compared to a control strategy that only adjusted the mode through the magnitude of interaction force, making the robot safer during the training process.

Targeted Temperature Management for Poor Grade Aneurysmal Subarachnoid Hemorrhage: A Pilot Study.

OBJECTIVE: We assessed the effectiveness and safety of target temperature management (TTM) in treating patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH). The primary objective was to evaluate the neurological outcome at 3 months. Secondary objectives were to assess mortality, delayed cerebral ischemia, cerebral edema, hydrocephalus, midline shift, and laboratory indicators related to TTM. METHODS: A single-blind, nonrandomized controlled trial was conducted. After admission, patients with poor-grade aSAH (Hunt-Hess scores IV âˆ¼ V) were assigned to a TTM group or a control group in a 1:1 ratio. TTM with core temperatures ranging from 36°C to 37°C was performed immediately and maintained until microclipping or endovascular embolization. Subsequently, rapid induction to 33°C ∼ 35°C was carried out and maintained for 3 to 5 days. Then, the patients underwent slow rewarming to 36°C ∼ 37°C and maintained at that temperature for a minimum of 48 hours. RESULTS: Sixty patients (30 treated with TTM and 30 with standard treatment) were included in the study. At 3 months, a favorable prognosis (modified Rankin scale score 0 to 3) was significantly higher in the TTM group than in the control group (n = 14, 46.7% vs. n = 6, 20.0%, P = 0.028). Adjusted multivariate logistics regression analysis indicated that TTM (odds ratio = 0.20, 95% confidence interval: 0.05-0.77, P = 0.019) reduced the number of unfavorable prognoses 3 months after admission. CONCLUSIONS: This study demonstrated the effectiveness and safety of TTM in patients with poor-grade aSAH, and its implementation improved neurological outcomes. Multicenter randomized controlled studies with a large number of patients are needed to confirm these observations.

Type of anesthesia for endovascular therapy in acute ischemic stroke: A literature review and meta-analysis.

BACKGROUND: Endovascular thrombectomy (EVT) has been proven as the standard treatment for acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO). However, the ideal anesthetic strategy during EVT still remains unclear. Therefore, this systematic review and meta-analysis aimed to determine the optimal anesthetic modality for patients with AIS undergoing EVT based on current randomized controlled trials (RCTs). METHODS: The databases Medline (via PubMed), EMBASE, Web of Science, and the Cochrane Library were searched for RCTs comparing general anesthesia (GA) and conscious sedation (CS) in AIS patients undergoing EVT. The primary outcome was a favorable functional outcome at 90 days postintervention. Data analysis was conducted using the Review Manager software (RevMan V.5.3). RESULTS: Eight RCTs involving 1199 patients were included. There was no significant difference between GA and CS group in the rate of functional independence (risk ratio (RR) = 1.10, 95% confidence interval (CI) = 0.96 to 1.25; p = 0.17; I2 = 30%). Compared with the CS group, the GA group attained a higher successful recanalization rate (RR = 1.14, 95% CI = 1.08 to 1.20; p < 0.00001; I2 = 17%). In addition, patients in the GA were associated with a higher rate of hypotension (RR = 1.87, 95% CI = 1.44 to 2.41; p < 0.00001; I2 = 66%) and a higher incidence of pneumonia (RR = 1.38, 95% CI = 1.05 to 1.8; p = 0.02; I2 = 37%). CONCLUSION: For AIS patients receiving EVT, the choice of anesthetic modality did not influence the 3-month neurological outcome while GA is superior to CS in terms of successful reperfusion rate. Moreover, the patients in the GA group were at a higher risk of developing hypotension and pneumonia. Further studies are required to provide more sufficient evidence.

Cascade hydroarylation/Diels-Alder cycloaddition of alkynylindoles with electron-deficient alkynes and alkenes.

Herein, a novel cascade gold(I)-catalyzed hydroarylation of alkynylindoles and subsequent Diels-Alder cycloaddition with electron-deficient alkynes and alkenes is described. A variety of azepino-fused hydrocarbazoles and carbazoles were obtained in moderate to excellent yields. Key features of this methodology are low catalyst loadings, high regioselectivity, broad functional group tolerances, access to important heterocycles, and 100% atom economy.

Constructing Fully-Active and Ultra-Active Sites in High-Entropy Alloy Nanoclusters for Hydrazine Oxidation-Assisted Electrolytic Hydrogen Production.

The development of sufficiently high-efficiency systems and effective catalysts for electrocatalytic hydrogen production is of great significance but challenging. Here, high-entropy alloy nanoclusters (HEANCs) with full-active sites and super-active sites are innovatively constructed for hydrazine oxidation-assisted electrolytic hydrogen production. The HEANCs show an average size of only seven atomic layers (1.48 nm). As the catalysts for both hydrogen evolution reaction (HER) and hydrazine oxidation reaction, the HEANC/C exhibits the best-level performance among reported electrocatalysts. Especially, the HEANC/C achieves an ultrahigh mass activity of 12.85 A mg-1 noble metals at -0.07 V and overpotential of only 9.5 mV for 10 mA cm-2 for alkaline HER. Further, with HEANC/C as both anode and cathode catalysts, an overall hydrazine oxidation-assisted splitting (OHzS) electrolyzer shows a record mass activity of 250.2 mA mg-1 catalysts at 0.1 V and only requires working voltages of 0.025 and 0.181 V to reach 10 and 100 mA cm-2, respectively, outperforming those of overall water-splitting system and other reported chemicals-assisted hydrogen production systems. Active site libraries including 72 sites on HEANC surface are originally constructed by theoretical calculations, revealing that all sites on HEANC surface are effective active sites for OHzS; especially some are super-active sites, endowing the best-level performance of HEANC/C.

Molecular Understanding of Charging Dynamics in Supercapacitors with Porous Electrodes and Ionic Liquids.

Porous electrodes and ionic liquids could significantly enhance the energy storage of supercapacitors. However, they may reduce the charging dynamics and power density due to the nanoconfinement of porous electrodes and the high viscosity of ionic liquids. A comprehensive understanding of the charging mechanism in porous supercapacitors with ionic liquids provides a crucial theoretical foundation for their design optimization. Here, we review the progress of molecular simulations of the charging dynamics in supercapacitors consisting of porous electrodes and ionic liquids. We highlight and delve into the breakthroughs in the ion transport and charging mechanism for electrodes with subnanometer pores and realistic porous structures. We also discuss future directions for the charging dynamics of supercapacitors.

Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism.

Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis.

A cross-sectional study of appropriateness evaluation of anticoagulation therapy for inpatients with nonvalvular atrial fibrillation.

Background: Oral anticoagulants (OACs) are essential for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the appropriateness of anticoagulation treatment in locally practice remains unclear. This study evaluated compliance with anticoagulation therapy concerning the guidelines and drug labels in patients with NVAF. Methods: Hospitalized patients diagnosed with NVAF between 1 November 2020, and 31 December 2021, were retrospectively enrolled. The appropriateness of anticoagulation regimens at discharge was evaluated based on a flowchart designed according to atrial fibrillation (AF) guidelines and medication labels. Furthermore, we explored factors potentially influencing the "no-use of OACs" using binary logistic regression and verified anticoagulation-related issues through a physician questionnaire. Results: A total of 536 patients were enrolled in this study, including 254 patients (47.4%) with inappropriate anticoagulation regimens. 112 patients (20.9%) were categorized as "underdosing-use of OACs," 134 (25%) who needed anticoagulation therapy were "no-use of OACs" and eight (1.5%) were "over-use of OACs." The results of a binary logistic regression analysis showed that paroxysmal AF (odds ratio [OR], 7.74; 95% confidence interval [CI], 4.57-13.10), increased blood creatinine levels (OR, 1.88; 95% CI, 1.11-3.16), hospitalized pacemaker implantation (OR, 6.76; 95% CI, 2.67-17.11), percutaneous coronary intervention (OR, 3.35; 95% CI, 1.44-7.80), and an increased HAS-BLED score (OR, 1.62; 95% CI, 1.11-2.35) were associated with "no-use of OACs" in patients with NVAF who had indications for anticoagulation therapy. Conclusion: For patients with NVAF with severe renal dysfunction and paroxysmal AF, anticoagulation therapy was inadequate. The underdosing-use of OACs in patients with NVAF was frequently observed. We recommend an anticoagulation management team to tailor anticoagulation regimens to suit each patient's needs.

Regulating the electrical double layer to prevent water electrolysis for wet ionic liquids with cheap salts.

Hydrophobic ionic liquids (ILs), broadly utilized as electrolytes, face limitations in practical applications due to their hygroscopicity, which narrows their electrochemical windows via water electrolysis. Herein, we scrutinized the impact of incorporating cheap salts on the electrochemical stability of wet hydrophobic ILs. We observed that alkali ions effectively manipulate the solvation structure of water and regulate the electrical double layer (EDL) structure by subtly adjusting the free energy distribution of water in wet ILs. Specifically, alkali ions significantly disrupted the hydrogen bond network, reducing free water, strengthening the O-H bond, and lowering water activity in bulk electrolytes. This effect was particularly pronounced in EDL regions, where most water molecules were repelled from both the cathode and anode with the disappearance of the H-bond network connectivity along the EDL. The residual interfacial water underwent reorientation, inhibiting water electrolysis and thus enhancing the electrochemical window of wet hydrophobic ILs. This theoretical proposition was confirmed by cyclic voltammetry measurements, demonstrating a 45% enhancement in the electrochemical windows for salt-in-wet ILs, approximating the dry one. This work offers feasible strategies for tuning the EDL and managing interfacial water activity, expanding the comprehension of interface engineering for advanced electrochemical systems.

SHCBP1 Promotes the Proliferation of Breast Cancer Cells by Inhibiting CXCL2.

Breast cancer has the characteristics of high metastasis and recurrence and ranks first in incidence and mortality among female malignant tumors. Shc SH2-domain binding protein 1 (SHCBP1) is an important protein in intracellular signal transduction and cell division, but the role of SHCBP1 in breast cancers remains elusive. Here, we found that SHCBP1 deficiency inhibited the proliferation of breast cancer cells. Mechanistically, SHCPB1 significantly downregulates the mRNA level of CXCL2, which in turn activates the AKT and ERK signaling, while inactivates the p21 and p27 signaling. In addition, overexpression of SHCPB1 downregulates the protein levels of p21 and p27, which could be completely reversed by restoration of CXCL2 expression. Moreover, we analyzed the expression of both SHCPB1 and CXCL2, and found that SHCPB1 is highly expressed in breast cancer cells or tissues from breast cancer patients compared to normal breast cells or adjacent normal tissues, while CXCL2 is lowly expressed in breast cancer cells or tissues. Collectively, our study reveals that SHCBP1 plays an oncogenic role in breast cancer tumorigenesis partially through inhibiting the inflammatory response and ultimately activating the proliferation of breast cancers.

Curtobacterium caseinilyticum sp. nov., Curtobacterium subtropicum sp. nov. and Curtobacterium citri sp. nov., isolated from citrus phyllosphere.

Three novel Gram-stain-positive, aerobic and rod-shaped bacterial strains, designated RHCKG28T, RHCJP20T and RHCKG23T, were isolated from phyllosphere of healthy citrus leaves collected from Renhua County in Guangdong Province, PR China. 16S rRNA gene sequences comparison and phylogenetic analyses showed that they all belonged to the genus Curtobacterium, among which strain RHCKG28T showed the highest similarity to Curtobacterium herbarum NBRC 103064T (99.3 %), while strains RHCJP20T and RHCKG23T showed 99.2 and 99.0 % similarity to Curtobacterium citreum JCM 1345T, respectively. Phylogenomic analysis showed that the three novel strains were most closely related to C. citreum JCM 1345T and Curtobacterium albidum JCM 1344T. The novel strains could be distinguished from their closely related type strains in terms of enzyme activities, substrate assimilation and fatty acid profiles. In addition, the average nucleotide identity and digital DNA-DNA hybridization values between the novel strains and closely related type strains were 84.4‒89.5 % and 24.5‒34.1 %, respectively, which were below the threshold values for species delimitation. They all took anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0 as the major fatty acids, menaquinone 9 (MK-9) as the sole predominant respiratory quinone, and ornithine as the principal cell-wall diamino acid. The major polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol and several unidentified glycolipids. The phenotypic, genotypic and chemotaxonomic data supported that they represent three distinct novel species of the genus Curtobacterium, for which the names Curtobacterium caseinilyticum sp. nov., Curtobacterium subtropicum sp. nov. and Curtobacterium citri sp. nov. are proposed, with RHCKG28T (=GDMCC 1.2667T=JCM 34828T), RHCJP20T (=GDMCC 1.2668T=JCM 34829T) and RHCKG23T (=GDMCC 1.2669T=JCM 34830T) as the type strains, respectively.

Safety, tolerability, and immunogenicity of a CpG/Alum adjuvanted SARS-CoV-2 recombinant protein vaccine (ZR202-CoV) in healthy adults: Preliminary report of a phase 1, randomized, double-blind, placebo-controlled, dose-escalation trial.

This was a phase 1 dose-escalation study of ZR202-CoV, a recombinant protein vaccine candidate containing a pre-fusion format of the spike (S)-protein (S-trimer) combined with the dual-adjuvant system of Alum/CpG. A total of 230 participants were screened and 72 healthy adults aged 18-59 years were enrolled and randomized to receive two doses at a 28-day interval of three different ZR202-CoV formulations or normal saline. We assessed the safety for 28 days after each vaccination and collected blood samples for immunogenicity evaluation. All formulations of ZR202-CoV were well-tolerated, with no observed solicited adverse events ≥ Grade 3 within 7 days after vaccination. No unsolicited adverse events ≥ Grade 3, or serious adverse events related to vaccination occurred as determined by the investigator. After the first dose, detectable immune responses were observed in all subjects. All subjects that received ZR202-CoV seroconverted at 14 days after the second dose by S-binding IgG antibody, pseudovirus and live-virus based neutralizing antibody assays. S-binding response (GMCs: 2708.7 ~ 4050.0 BAU/mL) and neutralizing activity by pseudovirus (GMCs: 363.1 ~ 627.0 IU/mL) and live virus SARS-CoV-2 (GMT: 101.7 ~ 175.0) peaked at 14 days after the second dose of ZR202-CoV. The magnitudes of immune responses compared favorably with COVID-19 vaccines with reported protective efficacy.

A novel C-type lectin (SpccCTL) suppresses MCRV replication by binding viral protein and regulating antiviral peptides in Scylla paramamosain.

Pattern recognition receptors (PRRs) play a crucial role in the recognition and activation of innate immune responses against invading microorganisms. This study characterizes a novel C-type lectin (CTL), SpccCTL. The cDNA sequence of SpccCTL has a full length of 1744 bp encoding a 338-amino acid protein. The predicted protein contains a signal peptide, a coiled-coil (CC) domain, and a CLECT domain. It shares more than 50 % similarity with a few CTLs with a CC domain in crustaceans. SpccCTL is highly expressed in gills and hemocytes and upregulated after MCRV challenge, suggesting that it may be involved in antiviral immunity. Recombinant SpccCTL (rSpccCTL) as well as two capsid proteins of MCRV (VP11 and VP12) were prepared. Pre-incubating MCRV virions with rSpccCTL significantly suppresses the proliferation of MCRV in mud crabs, compared with the control (treatment with GST protein), and the survival rate of mud crabs is also significantly decreased. Knockdown of SpccCTL significantly facilitates the proliferation of MCRV in mud crabs. These results reveal that SpccCTL plays an important role in antiviral immune response. GST pull-down assay result shows that rSpccCTL interacts specifically with VP11, but not to VP12. This result is further confirmed by a Co-IP assay. In addition, we found that silencing SpccCTL significantly inhibits the expression of four antimicrobial peptides (AMPs). Considering that these AMPs are members of anti-lipopolysaccharide factor family with potential antiviral activity, they are likely involved in immune defense against MCRV. Taken together, these findings clearly demonstrate that SpccCTL can recognize MCRV by binding viral capsid protein VP11 and regulate the expression of certain AMPs, suggesting that SpccCTL may function as a potential PRR playing an essential role in anti-MCRV immunity of mud crab. This study provides new insights into the antiviral immunity of crustaceans and the multifunctional characteristics of CTLs.