A novel bacterium-like particles platform displaying antigens by new anchoring proteins induces efficacious immune responses.

Bacterium-like particles (BLP) are the peptidoglycan skeleton particles of lactic acid bacteria, which have high safety, mucosal delivery efficiency, and adjuvant effect. It has been widely used in recent years in the development of vaccines. Existing anchoring proteins for BLP surfaces are few in number, so screening and characterization of new anchoring proteins are necessary. In this research, we created the OACD (C-terminal domain of Escherichia coli outer membrane protein A) to serve as an anchoring protein on the surface of BLP produced by the immunomodulatory bacteria Levilactobacillus brevis 23017. We used red fluorescent protein (RFP) to demonstrate the novel surface display system's effectiveness, stability, and ability to be adapted to a wide range of lactic acid bacteria. Furthermore, this study employed this surface display method to develop a novel vaccine (called COB17) by using the multi-epitope antigen of Clostridium perfringens as the model antigen. The vaccine can induce more than 50% protection rate against C. perfringens type A challenge in mice immunized with a single dose and has been tested through three routes. The vaccine yields protection rates of 75% for subcutaneous, 50% for intranasal, and 75% for oral immunization. Additionally, it elicits a strong mucosal immune response, markedly increasing levels of specific IgG, high-affinity IgG, specific IgA, and SIgA antibodies. Additionally, we used protein anchors (PA) and OACD simultaneous to show several antigens on the BLP surface. The discovery of novel BLP anchoring proteins may expand the possibilities for creating mucosal immunity subunit vaccines. Additionally, it may work in concert with PA to provide concepts for the creation of multivalent or multiple vaccines that may be used in clinical practice to treat complex illnesses.

Clinical, radiographic features and prognosis of cemental tear: A retrospective study of 63 teeth.

Cemental tears are often misdiagnosed due to their scarcity. In this study, we reported the second largest cohort of cemental tears thus far. By reviewing the radiographic data and medical records of 63 cemental tear teeth, we found that periapical periodontitis was the most frequent diagnosis, followed by cracked tooth/root fracture and periodontitis. Most of the cemental tear teeth that did not have root canal treatment had vital pulp. The apical third of the root was the most prominent site of cemental tears. Cemental tears occurred more frequently in the palatal root of the maxillary molars and in the mesial root of the two-root mandibular molars. Uncontrollable bone loss and tooth mobility were the two main reasons for the extraction of teeth with cemental tears. We suggest that cemental tears should be included in the differential diagnosis of periapical periodontitis, cracked tooth, vertical root fracture and periodontitis, especially for teeth with periapical radiolucency and vital pulp. We believe our study could provide more insights into cemental tears, which will aid clinicians in the early diagnosis and proper treatment of cemental tears.

Lactobacilli-derived adjuvants combined with immunoinformatics-driven multi-epitope antigens based approach protects against Clostridium perfringens in a mouse model.

Clostridium perfringens is ubiquitously distributed and capable of secreting toxins, posing a significant threat to animal health. Infections caused by Clostridium perfringens, such as Necrotic Enteritis (NE), result in substantial economic losses to the livestock industry annually. However, there is no effective commercial vaccine available. Hence, we set out to propose an effective approach for multi-epitope subunit vaccine construction utilizing biomolecules. We utilized immunoinformatics to design a novel multi-epitope antigen against C. perfringens (CPMEA). Furthermore, we innovated novel bacterium-like particles (BLPs) through thermal acid treatment of various Lactobacillus strains and selected BLP23017 among them. Then, we detailed the structure of CPMEA and BLPs and utilized them to prepare a multi-epitope vaccine. Here, we showed that our vaccine provided full protection against C. perfringens infection after a single dose in a mouse model. Additionally, BLP23017 notably augmented the secretion of secretory immunoglobulin A (sIgA) and enhanced antibody production. We conclude that our vaccine possess safety and high efficacy, making it an excellent candidate for preventing C. perfringens infection. Moreover, we demonstrate our approach to vaccine construction and the preparation of BLP23017 with distinct advantages may contribute to the prevention of a wider array of diseases and the novel vaccine development.

Proof of concept in utilizing the peptidoglycan skeleton of pathogenic bacteria as antigen delivery platform for enhanced immune response.

Subunit vaccines are becoming increasingly important because of their safety and effectiveness. However, subunit vaccines often exhibit limited immunogenicity, necessitating the use of suitable adjuvants to elicit robust immune responses. In this study, we demonstrated for the first time that pathogenic bacteria can be prepared into a purified peptidoglycan skeleton without nucleic acids and proteins, presenting bacterium-like particles (pBLP). Our results showed that the peptidoglycan skeletons screened from four pathogens could activate Toll-like receptor1/2 receptors better than bacterium-like particles from Lactococcus lactis in macrophages. We observed that pBLP was safe in mouse models of multiple ages. Furthermore, pBLP improved the performance of two commercial vaccines in vivo. We confirmed that pBLP successfully loaded antigens onto the surface and proved to be an effective antigen delivery platform with enhanced antibody titers, antibody avidity, balanced subclass distribution, and mucosal immunity. These results indicate that the peptidoglycan skeleton of pathogenic bacteria represents a new strategy for developing subunit vaccine delivery systems.

Super flexible, self-healing, and self-adhesive double network hydrogel reinforced by okara cellulose nanofibrils.

Inspired by the mussel, tannic acid (TA) was modified onto the surface of self-made cellulose nanofibrils (CNFs) to prepare TA@CNFs, which was introduced into borax crosslinked polyvinyl alcohol (PVA) to prepare PTC double-network hydrogel with self-healing properties. Through the comparative observation of TEM images and infrared spectra before and after tannic acid modification, the formation of TA@CNFs was proved. The introduction of TA@CNFs greatly increases the fracture stress of PTC hydrogel, which is more than 10 times higher than that of PVA hydrogel without TA@CNFs, and has high fracture strain (1723 %). Moreover, PTC hydrogel has the ability of rapid self-healing, which can heal to the original form within two minutes. In addition, the temperature response ability of PTC hydrogel makes it capable of reshaping. The self-adhesion ability of PTC hydrogel enables it to adhere to the human epidermis to detect motion signals, as sensitive and as stable as a flexible sensor.

Correction of a CADASIL point mutation using adenine base editors in hiPSCs and blood vessel organoids.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic small vessel disease caused by mutations in the NOTCH3 gene. However, the pathogenesis of CADASIL remains unclear, and patients have limited treatment options. Here, we use human induced pluripotent stem cells (hiPSCs) generated from the peripheral blood mononuclear cells of a patient with CADASIL carrying a heterozygous NOTCH3 mutation (c.1261C>T, p.R421C) to develop a disease model. The correction efficiency of different adenine base editors (ABEs) is tested using the HEK293T-NOTCH3 reporter cell line. ABEmax is selected based on its higher efficiency and minimization of predicted off-target effects. Vascular smooth muscle cells (VSMCs) differentiated from CADASIL hiPSCs show NOTCH3 deposition and abnormal actin cytoskeleton structure, and the abnormalities are recovered in corrected hiPSC-derived VSMCs. Furthermore, CADASIL blood vessel organoids generated for in vivo modeling show altered expression of genes related to disease phenotypes, including the downregulation of cell adhesion, extracellular matrix organization, and vessel development. The dual adeno-associated virus (AAV) split-ABEmax system is applied to the genome editing of vascular organoids with an average editing efficiency of 8.82%. Collectively, we present potential genetic therapeutic strategies for patients with CADASIL using blood vessel organoids and the dual AAV split-ABEmax system.

Effect of acupuncture on regulating IL-17, TNF-ɑ and AQPs in Sjögren's syndrome.

AIM: The aim of the study was to observe the effect of acupuncture on regulating interleukin (IL)-17, tumor necrosis factor (TNF)-ɑ, and aquaporins (AQPs) in Sjögren's syndrome (SS) on patients and on non-obese diabetic (NOD) models. METHODS: Levels of anti-AQP 1, 5, 8, and 9 antibodies, IL-17, and TNF-ɑ in the serum of SS patients were compared prior and following 20 acupuncture treatment visits during 8 weeks. While in murine model, five groups were divided to receive interventions for 4 weeks, including control, model, acupuncture, isoflurane, and hydroxychloroquine. The submaxillofacial gland index, histology, immunohistochemistry of AQP1, 5, salivary flow, together with IL-17, and TNF-ɑ expression in peripheral blood were compared among the groups. RESULTS: Acupuncture reduced IL-17, TNF-ɑ, and immunoglobin A levels, and numeric analog scale of dryness in 14 patients with SS (p < 0.05). The salivary flow was increased, and the water intake decreased in NOD mice receiving acupuncture treatments. IL-17 and TNF-ɑ levels in peripheral serum were down-regulated (p < 0.05) and AQP1, 5 expression in the submandibular glands up-regulated in mice. CONCLUSION: The effect on relieving xerostomia with acupuncture may be achieved by up-regulating the expression of AQP1. AQP5, down-regulating levels of IL-17 and TNF-ɑ, and a decrease in inflammation of glands.

Chiral metal-organic frameworks incorporating nanozymes as neuroinflammation inhibitors for managing Parkinson's disease.

Nanomedicine-based anti-neuroinflammation strategy has become a promising dawn of Parkinson's disease (PD) treatment. However, there are significant gaps in our understanding of the therapeutic mechanisms of antioxidant nanomedicines concerning the pathways traversing the blood-brain barrier (BBB) and subsequent inflammation mitigation. Here, we report nanozyme-integrated metal-organic frameworks with excellent antioxidant activity and chiral-dependent BBB transendocytosis as anti-neuroinflammatory agents for the treatment of PD. These chiral nanozymes are synthesized by embedding ultra-small platinum nanozymes (Ptzymes) into L-chiral and D-chiral imidazolate zeolite frameworks (Ptzyme@L-ZIF and Ptzyme@D-ZIF). Compared to Ptzyme@L-ZIF, Ptzyme@D-ZIF shows higher accumulation in the brains of male PD mouse models due to longer plasma residence time and more pathways to traverse BBB, including clathrin-mediated and caveolae-mediated endocytosis. These factors contribute to the superior therapeutic efficacy of Ptzyme@D-ZIF in reducing behavioral disorders and pathological changes. Bioinformatics and biochemical analyses suggest that Ptzyme@D-ZIF inhibits neuroinflammation-induced apoptosis and ferroptosis in damaged neurons. The research uncovers the biodistribution, metabolic variances, and therapeutic outcomes of nanozymes-integrated chiral ZIF platforms, providing possibilities for devising anti-PD drugs.

Bacterium-like particles derived from probiotics: progress, challenges and prospects.

Bacterium-like particles (BLPs) are hollow peptidoglycan particles obtained from food-grade Lactococcus lactis inactivated by hot acid. With the advantage of easy preparation, high safety, great stability, high loading capacity, and high mucosal delivery efficiency, BLPs can load and display proteins on the surface with the help of protein anchor (PA), making BLPs a proper delivery system. Owning to these features, BLPs are widely used in the development of adjuvants, vaccine carriers, virus/antigens purification, and enzyme immobilization. This review has attempted to gather a full understanding of the technical composition, characteristics, applications. The mechanism by which BLPs induces superior adaptive immune responses is also discussed. Besides, this review tracked the latest developments in the field of BLPs, including Lactobacillus-derived BLPs and novel anchors. Finally, the main limitations and proposed breakthrough points to further enhance the immunogenicity of BLPs vaccines were discussed, providing directions for future research. We hope that further developments in the field of antigen delivery of subunit vaccines or others will benefit from BLPs.

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction.

Fetal growth restriction (FGR) is associated with increased susceptibility to perinatal morbidity and mortality. Evidence suggests that epigenetic changes play critical roles in the regulation of fetal growth. We sought to present a comprehensive analysis of the associations between placental DNA methylation and selective fetal growth restriction (sFGR), which is a severe complication of monochorionic twin pregnancies, characterized by one fetus experiencing restricted growth. Genome-wide methylation analysis was performed on 24 placental samples obtained from 12 monochorionic twins with sFGR (Cohort 1) using Illumina Infinium MethylationEPIC BeadChip. Integrative analysis of our EPIC data and two previous placental methylation studies of sFGR (a total of 30 placental samples from 15 sFGR twins) was used to identify convincing differential promoter methylation. Validation analysis was performed on the placentas from 15 sFGR twins (30 placental samples), 15 FGR singletons, and 14 control singletons (Cohort 2) using pyrosequencing, quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry (IHC). A globe shift toward hypomethylation was identified in the placentas of growth-restricted fetuses compared with the placentas of normal fetuses in monochorionic twins, including 5625 hypomethylated CpGs and 452 hypermethylated CpGs, especially in the regions of CpG islands, gene-body and promoters. The analysis of pathways revealed dysregulation primarily in steroid hormone biosynthesis, metabolism, cell adhesion, signaling transduction, and immune response. Integrative analysis revealed a differentially methylated promoter region in the CYP11A1 gene, encoding a rate-limiting enzyme of steroidogenesis converting cholesterol to pregnenolone. The CYP11A1 gene was validated to have hypomethylation and higher mRNA expression in sFGR twins and FGR singletons. In conclusion, our findings suggested that the changes in placental DNA methylation pattern in sFGR may have functional implications for differentially methylated genes and regulatory regions. The study provides reliable evidence for identifying abnormally methylated CYP11A1 gene in the placenta of sFGR.

Extraction of impacted mandibular third molars in close proximity to the inferior alveolar canal with coronectomy-miniscrew traction to avoid nerve injury.

OBJECTIVES: Extraction of impacted mandibular third molars (IMTMs) is the most common surgery performed in the Department of Oral and Maxillofacial Surgery. Inferior alveolar nerve (IAN) injury is a rare but severe complication, and the risk is significantly higher in cases of IMTM near the inferior alveolar canal (IAC). The existing surgical method to extract such IMTMs is either not safe enough or is time-consuming. A better surgical design is needed. MATERIALS AND METHODS: From August 2019 to June 2022, 23 patients underwent IMTM extraction by Dr. Zhao at Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, and were found to have IMTMs in close proximity to the IAC. Due to high IAN injury risk, these patients underwent coronectomy-miniscrew traction to extract their IMTMs. RESULTS: The time between coronectomy-miniscrew insertion and complete removal of the IMTM was 32.65 ± 2.110 days, which was significantly shorter than that of traditional orthodontic traction. Two-point discrimination testing revealed no IAN injury, and no injury was reported by patients during follow-up. Other complications, such as severe swelling, severe bleeding, dry socket, and limited mouth opening, were not observed. Postoperative pain levels were not significantly higher in the coronectomy-miniscrew traction group than in the traditional IMTM extraction group. CLINICAL RELEVANCE: For IMTMs that are in close proximity to the IAC and must be extracted, coronectomy-miniscrew traction is a novel approach to minimize the risk of IAN injury in a less time-consuming way with a lower possibility of complications.

Chromosomal abnormalities in recurrent pregnancy loss and its association with clinical characteristics.

OBJECTIVE: To evaluate the distribution of chromosomal abnormalities in a recurrent pregnancy loss (RPL) cohort and explore the associations between chromosomal abnormalities and clinical characteristics. METHOD: Over a 5-year period, fresh products of conception (POC) from women with RPL were analyzed by single-nucleotide polymorphism (SNP) array at our hospital. After obtaining the information on clinical characteristics, we investigated the associations between the causative chromosomal abnormalities and clinical characteristics by the chi-squared test or Fisher's exact test and logistic regression. RESULTS: A total of 2383 cases were enrolled. Overall, 56.9% (1355/2383) were identified with causative chromosomal abnormalities, of which 92.1% (1248/1355) were numerical abnormalities, 7.5% (102/1355) were structural variants, and 0.4% (5/1355) were loss of heterozygosity (LOH). The risk of numerical abnormalities was increased in women with maternal age ≥ 35 years (OR, 1.71; 95% CI, 1.41-2.07), gestational age at pregnancy loss ≤ 12 weeks (OR, 2.78; 95% CI, 1.79-4.33), less number of previous pregnancy losses (twice: OR, 2.32; 95% CI, 1.84-2.94; 3 times: OR, 1.59; 95% CI, 1.23-2.05, respectively), and pregnancy with a female fetus (OR, 1.37; 95% CI, 1.15-1.62). The OR of pregnancy loss with recurrent abnormal CMA was 4.00 (95% CI: 1.87-8.58, P < 0.001) and the adjusted OR was 5.05 (95% CI: 2.00-12.72, P = 0.001). However, the mode of conception was not associated with the incidence of numerical abnormality. No association was noted between structural variants and clinical characteristics. CONCLUSION: Chromosomal abnormality was the leading cause of RPL. Numerical chromosome abnormality was more likely to occur in cases with advanced maternal age, an earlier gestational age, fewer previous pregnancy losses, and pregnancy with a female fetus.

Dynamics of T follicular helper cells in patients with rheumatic diseases and subsequent antibody responses in a three-dose immunization regimen of CoronaVac.

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.

Employability, organizational commitment and person-organization fit among nurses in China: A correctional cross-sectional research.

AIM: This study aimed to explore the effect of training on organizational commitment, the mediating effect of employability and the moderating role of person-organization fit. DESIGN: A correctional cross-sectional research design was adopted for this study. METHODS: A questionnaire-based survey of 859 nurses in a public hospital in Western China was conducted to identify their perceptions of training, employability, organizational commitment and person-organization fit. Hierarchical linear regression and conditional process analysis on moderated mediation were performed. RESULTS: Training had a positive effect on organizational commitment (p < .01). Internal and external employability mediated the relationship between training and organizational commitment (p < .01). Person-organization fit enhanced the indirect effect of training on organizational commitment through external employability (p < .05).

An Investigation of the Etiologies of Non-Immune Hydrops Fetalis in the Era of Next-Generation Sequence-A Single Center Experience.

(1) Background: Numerous etiologies may lead to non-immune hydrops fetalis (NIHF). However, the causes remain unclear in half of NIHF cases following current standard assessment. The application of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) can improve the identification of the etiologies. This study aimed to investigate the etiologies of NIHF in the era of next-generation sequence (NGS) following a unified prenatal work-up flow for diagnosis. (2) Methods: A retrospective analysis was conducted on NIHF cases that were collected prospectively to explore the underlying etiologies according to a unified prenatal diagnosis work-up flow at Shanghai First Maternity and Infant Hospital between Jan 2016 and Dec 2019. The medical records for all NIHF cases were reviewed, and the causes of NIHF were classified as confirmed (diagnostic), suspected, or unknown. (3) Results: Prenatal and postnatal medical records for a total of 145 NIHF cases were reviewed, 48.3% (70/145) of the cases were identified to be with confirmed etiologies, and 10.3% (15/145) with suspected etiologies. Among 85 cases with confirmed or suspected etiologies, 44.7% were diagnosed with genetic disorders, 20% with chylothorax/chyloascites diagnosed postnatally, 12.9% with fetal structural anomalies, 12.9% with fetal anemia, 7% (6 cases) with fetal arrhythmia, and 2.3% (2 cases) with placenta chorioangioma. In cases with genetic disorders, 8 aneuploidies were detected by CMA, and 30 cases had single-gene disorders identified by ES (29/30) or targeted gene panel (1/30). There were still 41.4% cases (60/145) with unknown causes after this unified prenatal diagnostic work-up flow. (4) Conclusions: In the era of NGS, the causes of NIHF were identified in 58.6% of cases, with genetic disorders being the most common ones. NGS is helpful in determining the genetic etiology of NIHF when CMA results cannot explain NIHF, but 41.4% of cases were still with unknown causes under the unified prenatal diagnostic work-up flow in this single-center study.

The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease defined by exocrine gland hypofunction resulting in dry eyes and dry mouth. Despite increasing interest in biological therapies for pSS, achieving FDA-approval has been challenging due to numerous complications in the trials. The current literature lacks insight into a molecular-target-based approach to the development of biological therapies. This review focuses on novel research in newly defined drug targets and the latest clinical trials for pSS treatment. A literature search was conducted on ClinicalTrials.gov using the search term "Primary Sjögren's syndrome". Articles published in English between 2000 and 2021 were included. Our findings revealed potential targets for pSS treatment in clinical trials and the most recent advances in understanding the molecular mechanisms underlying the pathogenesis of pSS. A prominent gap in current trials is in overlooking the treatment of extraglandular symptoms such as fatigue, depression, and anxiety, which are present in most patients with pSS. Based on dryness and these symptom-directed therapies, emerging biological agents targeting inflammatory cytokines, signal pathways, and immune reaction have been studied and their efficacy and safety have been proven. Novel therapies may complement existing non-pharmacological methods of alleviating symptoms of pSS. Better grading systems that add extraglandular symptoms to gauge disease activity and severity should be created. The future of pSS therapies may lie in gene, stem-cell, and tissue-engineering therapies.

Emotional exhaustion and unhealthy eating among COVID-19 front-line healthcare workers during recuperation: A cross-sectional study.

Objective: Thousands of healthcare workers on the frontlines who have been battling the COVID-19 pandemic could face emotional and mental health risks even after their critical pandemic work. This study examined the impact of affective rumination on emotional exhaustion and the spillover effect of affective rumination on unhealthy food consumption among healthcare workers during recuperation. Methods: A total of 418 frontline healthcare workers from 10 Chinese medical institutions were recruited through random cluster sampling. A linear mixed model in SPSS25.0 was performed for hierarchical regression to analyze the effect of affective rumination on unhealthy food consumption via emotional exhaustion. A conditional process analysis was employed to investigate the moderating role of family support in the mediating effect of emotional exhaustion. Results: Front-line healthcare workers scored at a medium level on an emotional exhaustion scale (2.45 ± 0.88). Affective rumination mediated by emotional exhaustion had a significant positive predictive effect on unhealthy food consumption. The indirect effect accounted for ~43.9% of the total effect. Family support amplified the effect of emotional exhaustion on unhealthy food consumption (ß = 0.092, p < 0.05). Conclusion: Affective rumination could be a cause of emotional exhaustion and unhealthy food consumption. First-line healthcare workers could be screened for possible emotional exhaustion through the evaluation of affective rumination in order to provide them with targeted interventions. Family support did not prove to be beneficial in all cases as it enhanced the positive effect of emotional exhaustion on unhealthy eating in the current study. Therefore, family support should be carefully integrated in future interventions.

Edge-Site Engineering of Defective Fe-N4 Nanozymes with Boosted Catalase-Like Performance for Retinal Vasculopathies.

Extensive efforts are devoted to refining metal sites for optimizing the catalytic performance of single-atom nanozymes (SANzymes), while the contribution of the defect environment of neighboring metal sites lacks attention. Herein, an iron-based SANzyme (Fe-SANzyme) is rationally designed by edge-site engineering, which intensively exposes edge-hosted defective Fe-N4 atomic sites anchored in hierarchical mesoporous structures. The Fe-SANzyme exhibits excellent catalase-like activity capable of efficiently catalyzing the decomposition of H2 O2 into O2 and H2 O, with a catalytic kinetic KM value superior to that of natural catalase and reported nanozymes. The mechanistic studies depict that the defects introduce notable charge transfer from the Fe atom to the carbon matrix, making the central Fe more activated to strengthen the interaction with H2 O2 and weaken the OO bond. By performing catalase-like catalysis, the Fe-SANzyme significantly scavenges reactive oxygen species (ROS) and alleviates oxidative stress, thus eliminating the pathological angiogenesis in animal models of retinal vasculopathies without affecting the repair of normal vessels. This work provides a new way to refine SANzymes by engineering the defect environment and geometric structure around metal sites, and demonstrates the potential therapeutic effects of the nanozyme on retinal vasculopathies.

The effect of hindrance stressors on the emotional exhaustion among front-line healthcare workers in the recuperation period during the COVID-19 epidemic in China: a prospective cross-sectional study.

OBJECTIVES: This study aimed to examine the influence and conditioning process of hindrance stressors on the emotional exhaustion of the front-line healthcare workers during recuperation, examine the potential mediating process of rumination, and explore the moderating role of organisational and family factors. SETTING: This cross-sectional study was conducted during 12-20 July 2020. Total 418 questionnaires were collected from front-line healthcare workers by random cluster sampling. Hierarchical regression was performed to analyse the mediating effect of affective rumination using SPSS25.0, while PROCESS was used to further investigate the moderating role of servant leadership and family support. PARTICIPANTS: 418 healthcare workers were investigated randomly from front-line medical teams. Inclusion criteria included worked as front-line health workers and participated in the fight against COVID-19 in Hubei; age ≥18 years; normal cognitive and comprehension abilities under physical and mental health; volunteer to participate in this study. Exclusion criteria included recently affected by major events other than COVID-19 or those with a history of neurasthenia and trauma. RESULTS: Using descriptive analysis of average value and SD measured by a five-item scale (MBI-GS), we found that front-line healthcare workers' emotional exhaustion score (2.45±0.88) was at the medium level. Hindrance stressors, mediated by affective rumination, had a significant positive predictive effect on emotional exhaustion. Servant leadership negatively moderated the direct effect of hindrance stressors on emotional exhaustion (ß=-0.106, p<0.01). Family support positively moderated the impact of hindrance stressors on emotional exhaustion (ß=0.082, p<0.05). CONCLUSIONS: During the recuperation period, after successfully controlling COVID-19 at the front line, the first-line healthcare workers should be screened through affective rumination evaluation to gain insight for targeted interventions. We find that servant leadership is beneficial in alleviating emotional exhaustion while family support worsens emotional exhaustion. We suggest that servant leadership should be further promoted in medical organisations, and family support should be applied correctly and cautiously.

Efficacy and Safety of Acupuncture on Symptomatic Improvement in Primary Sjögren's Syndrome: A Randomized Controlled Trial.

Aim: We sought to evaluate the efficacy of acupuncture in treating the main symptoms of primary Sjögren's syndrome, specifically dryness, pain, and fatigue. Methods: A total of 120 patients with primary Sjögren's syndrome were randomized in a parallel-group, controlled trial. Participants received acupuncture or sham acupuncture for the first 8 weeks, then were followed for 16 weeks thereafter. The primary outcome was the proportion of participants with a ≥ 30% reduction in ≥ 2 of 3 numeric analog scale scores for dryness, pain, and fatigue. The secondary outcomes included the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient-reported Index (ESSPRI); the EULAR Sjögren's Syndrome Disease Activity Index; the Schirmer test score; unstimulated saliva flow; serum immunoglobulin G, A, and M concentrations; the Medical Outcome Study Short Form 36 score; salivary gland ultrasound imaging; and the Hospital Anxiety and Depression Scale score. Results: The proportions of patients meeting the primary endpoint were 28.33% (17/60) in the acupuncture group and 31.66% (19/60) in the sham group, without a statistically significant difference (P = 0.705). The IgG concentration at week 16 and the homogeneity in ultrasonography of the salivary glands at week 8 showed significant differences between the 2 groups (P = 0.0490 and P = 0.0334, respectively). No other differences were observed between the 2 groups. ESSPRI and unstimulated saliva flow were improved in both groups compared to baseline, albeit with a significant difference between them. Conclusion: In patients with primary Sjögren's syndrome, acupuncture did not satisfactorily improve symptoms compared to placebo. However, interesting discoveries and possible underlying reasons were demonstrated and discussed, which may be useful to studies in the future. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT02691377].