The emergence of severe cases of human influenza A (H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this study, ...a cold-adapted (ca), live attenuated monovalent reassortant influenza H7N9 virus (Ah01/AA ca) was generated using reverse genetics that contained hemagglutinin (HA) and neuraminidase (NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus (Ah01/H7N9); the remaining six backbone genes derived from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus (AA virus). Ah01/AA ca virus exhibited temperature sensitivity (ts), ca, and attenuation (att) phenotypes. Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cell-mediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9 (A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the further evaluation of this Ah01/AA ca candidate vaccine in primates.
R5; AIM:To investigate the possibilities and advantages of laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct compaired with ...traditional open operation.METHODS:Laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct and traditional open operation were performed in two groups of patients who had gallstones in the left lobe of liver and in the common bile duct.The hospitalization time,hospitalization costs,operation time,operative complications and post-operative liver functions of the two groups of patients were studied.RESULTS:The operation time and post-operative liver functions of the two groups of patients had no significant differences,while the hospitalization time,hospitalization costs and operative complications of the laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration in the common bile duct group were significantly lower than those in the traditional open operation group.CONCLUSION:For patients with gallstones in the left lobe of liver and in the common bile duct,laparoscopic hepatic left lateral Iobectomy combined with fiber choledochoscopic exploration of the common bile duct can significantly shorten the hospitalization time,reduce the hospitalization costs and the post-operative complications,without prolonging the operation time and bringing about more liver function damages compared with traditional open operation.This kind of operation has more advantages than traditional open operation.
Ensuring the patency of repaired vessels is pivotal in improving the success rate of digit replantation. There is no consensus on how to best approach postoperative treatment for digit replantation. ...The influence of postoperative treatment on the risk of failure of revascularization or replantation remains unclear.
(1) Is there an increased risk of postoperative infection with early discontinuation of antibiotic prophylaxis? (2) How are anxiety and depression affected by a treatment protocol consisting of prolonged antibiotic prophylaxis and administration of antithrombotic and antispasmodic drugs and by the failure of a revascularization or replantation procedure? (3) Are there differences in the risk of revascularization or replantation failure based on the number of anastomosed arteries and veins? (4) What factors are associated with failure of revascularization or replantation?
This retrospective study was conducted between July 1, 2018, and March 31, 2022. Initially, 1045 patients were identified. One hundred two patients chose revision of amputation. In all, 556 were excluded because of contraindications. We included all patients in whom the anatomic structures of the amputated part of the digit were well preserved, and those with an ischemia time for the amputated part that did not exceed 6 hours. Patients in good health without any other serious associated injuries or systemic diseases and those without a history of smoking were eligible for inclusion. The patients underwent procedures that were performed or supervised by one of four study surgeons. Patients were treated with antibiotic prophylaxis (1 week); patients treated with antithrombotic and antispasmodic drugs were categorized into the prolonged antibiotic prophylaxis group. The remaining patients treated with antibiotic prophylaxis for less than 48 hours and no antithrombotic and no antispasmodic drugs were categorized into the nonprolonged antibiotic prophylaxis group. Postoperative follow-up was for a minimum of 1 month. Based on the inclusion criteria, 387 participants with 465 digits were selected for an analysis of postoperative infection. Twenty-five participants with a postoperative infection (six digits) and other complications (19 digits) were excluded from the next stage of the study, in which we assessed factors associated with the risk of failure of revascularization or replantation. A total of 362 participants with 440 digits were examined, including the postoperative survival rate, variation in Hospital Anxiety and Depression Scale scores, the association between the survival rate and Hospital Anxiety and Depression Scale scores, and the survival rate based on the number of anastomosed vessels. Postoperative infection was defined as swelling, erythema, pain, purulent discharge, or a positive bacterial culture result. Patients were followed for 1 month. The differences in anxiety and depression scores between the two treatment groups and the differences in anxiety and depression scores based on failure of revascularization or replantation were determined. The difference in the risk of revascularization or replantation failure based on the number of anastomosed arteries and veins was assessed. Except for statistically significant variables (injury type and procedure), we thought that the number of arteries, number of veins, Tamai level, treatment protocol, and surgeons would be important. A multivariable logistic regression analysis was used to perform an adjusted analysis of risk factors such as postoperative protocol, injury type, procedure, number of arteries, number of veins, Tamai level, and surgeon.
Postoperative infection did not appear to increase without prolonged use of antibiotic prophylaxis beyond 48 hours (1% 3 of 327 versus 2% 3 of 138; OR 2.4 95% confidence interval (CI) 0.5 to 12.0; p = 0.37). Intervention with antithrombotic and antispasmodic therapy increased the Hospital Anxiety and Depression Scale scores for anxiety (11.2 ± 3.0 versus 6.7 ± 2.9, mean difference 4.5 95% CI 4.0 to 5.2; p < 0.01) and depression (7.9 ± 3.2 versus 5.2 ± 2.7, mean difference 2.7 95% CI 2.1 to 3.4; p < 0.01). In the analysis based on the failure of revascularization or replantation, the Hospital Anxiety and Depression Scale scores for anxiety (11.4 ± 4.4 versus 9.7 ± 3.5, mean difference 1.7 95% CI 0.6 to 2.8; p < 0.01) and depression (8.5 ± 4.6 versus 7.0 ± 3.1, mean difference 1.5 95% CI 0.5 to 2.5; p < 0.01) were higher in the failed revascularization or replantation group than in the successful revascularization or replantation group. There was no increase in the artery-related risk of failure (one versus two anastomosed arteries: 91% versus 89%, OR 1.3 95% CI 0.6 to 2.6; p = 0.53). For patients with anastomosed veins, a similar outcome was observed for the two vein-related risk of failure (two versus one anastomosed vein: 90% versus 89%, OR 1.0 95% CI 0.2 to 3.8; p = 0.95) and three vein-related risk of failure (three versus one vein anastomosed: 96% versus 89%, OR 0.4 95% CI 0.1 to 2.4; p = 0.29). Factors associated with failure of revascularization or replantation included the mechanism of injury (crush: OR 4.2 95% CI 1.6 to 11.2; p < 0.01, avulsion: OR 10.2 95% CI 3.4 to 30.7; p < 0.01). Revascularization had a lower risk of failure than replantation (OR 0.4 95% CI 0.2 to 1.0; p = 0.04). Treatment with a protocol of prolonged antibiotics, antithrombotics, and antispasmodics was not associated with a lower risk of failure (OR 1.2 95% CI 0.6 to 2.3; p = 0.63).
With proper wound debridement and patency of repaired vessels, prolonged use of antibiotic prophylaxis and regular antithrombotic and antispasmodic treatment may not be necessary for successful digit replantation. However, it may be associated with higher Hospital Anxiety and Depression Scale scores. Postoperative mental status is associated with digit survival. Well-repaired vessels, instead of the number of anastomosed vessels, could be critical to survival and decrease the influence of risk factors. Further research on consensus guidelines that compare postoperative treatment and the surgeon's level of expertise after digit replantation should be conducted at multiple institutions.
Level III, therapeutic study.
The single-flow zinc–nickel battery (ZNB) is a new type of flow battery with a simple structure, large-scale energy storage, and low cost, and thus has attracted much attention in the battery field ...recently. The state of charge (SOC) and state of health (SOH) are key indicators of the battery, and their inaccurate estimation can damage the battery. However, little has been done so far to study how to jointly estimate SOC and SOH for the ZNB. In this paper, the method of adaptive IDUKF is proposed. A second-order equivalent circuit model is applied to improve the accuracy. At the same time, the double unscented Kalman filter (DUKF), which is optimized by the improved Harris hawk optimization (IHHO) algorithm, is used to estimate the SOC and parameters online. Then, the capacity update model is introduced to simulate the change in SOH. Finally, the proposed method is applied to a 16 Ah ZNB, and the experimental results confirm the validity of the proposed method.
Sperm acrosomal membrane proteins, such as Izumo sperm-egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. How their ...biosynthesis is regulated during spermiogenesis has largely remained elusive. Here, we show that
knockout male mice are severely subfertile and their spermatozoa do not fuse with eggs. 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. It interacts with proteins involved in
-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. The ablation of
destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for
-glycosylation. The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis.
The development of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two ...multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines, and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against COVID-19.
Background
Segmentectomy has been proven to have better survival and perioperative efficacy than lobectomy for non-small cell lung cancer (NSCLC) up to 2 cm. Whether this result is applicable to ...stage T1cN0M0 NSCLC (2.1 to 3 cm) remains controversial.
Methods
We conducted a comprehensive search across seven databases to identify relevant studies comparing lobectomy and segmentectomy procedures. Our primary focus was on survival indicators (overall survival OS and disease-free survival DFS), while for secondary outcomes, operative outcomes, hospitalization outcomes, recurrences, and complications were considered.
Results
After screening, the final analysis included 10 studies (involving 22113 patients in the lobectomy group and 1627 patients in the segmentectomy group). The lobectomy procedure achieved better OS (hazard ratio HR: 1.19 1.07~1.33) and DFS (HR: 1.37 1.10~1.71), which were proven in all subgroups. The OS rate at 2-5 years and DFS rate at 4-5 years were higher in the lobectomy group. The advantages of OS and DFS in the lobectomy group increased over the survival time. More lymph node dissections, intraoperative blood loss and total complications were found in the lobectomy group. Similar hospital stays, 90-day mortality and conversion thoracotomy were found between the two groups.
Conclusion
Lobectomy appeared to be the better choice for patients with stage T1cN0M0 NSCLC with better survival (OS and DFS). However, the complications needed to be taken seriously.
Systematic review registration
https://www.crd.york.ac.uk/PROSPERO/
, identification CRD42023445013.
Esophageal squamous cell carcinoma (ESCC) has still been considered to be the most common malignant tumors in China. Emerging evidence indicates that cysteinyl-tRNA synthetase 1 (CARS1) has been ...considered as a ferroptosis-related gene in ESCC. However, the roles and molecular mechanisms of CARS1 in ferroptosis-induced cell death of ESCC are still largely unknown. In our study, we investigated an aberrantly upregulated gene in ESCC tumor tissues CARS1 significantly inhibited cell proliferation, and the ability of migration and invasion promoted the relative level of MDA and ROS and decreased GPX4 expression level in two ESCC cell lines. Mechanistically, both the ferroptosis inhibitor ferrostatin-1 and its inducer erastin were further used and indicated that CARS1 participated in the ferroptosis-induced cell death. Together, these results revealed that CARS1 has a critical function in the progression of ESCC by promoting ferroptosis-induced cell death.
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