Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines.

Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p < 0.001). In the Sf9 cells group, GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses (prototype and diverse variants of concern [VOCs]) increased by 22.23-75.93 folds from baseline to day 28 post-booster, while the CoronaVac group showed increases of only 3.29-10.70 folds. Similarly, neutralizing antibodies against live SARS-CoV-2 viruses (prototype and diverse VOCs) increased by 68.18-192.67 folds on day 14 post-booster compared with the baseline level, significantly greater than the CoronaVac group (19.67-37.67 folds). A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster (mean IFN-γ+ spot-forming cells per 2 × 105 peripheral blood mononuclear cells: 26.66 vs. 13.59). Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group (68.18% vs. 36.59%, p = 0.004). Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine (Sf9 cells) against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern, while causing no apparent safety concerns.

A Dual-domain Engineered Antibody for Efficient HBV Suppression and Immune Responses Restoration.

Chronic hepatitis B (CHB) remains a major public health concern because of the inefficiency of currently approved therapies in clearing the hepatitis B surface antigen (HBsAg). Antibody-based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual-domain-engineered anti-hepatitis B virus (HBV) therapeutic antibody 73-DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV-tolerant mice, administration of a single dose of 73-DY at 2 mg kg-1 is sufficient to reduce serum HBsAg by over 3 log10 IU mL-1 and suppress HBsAg to < 100 IU mL-1 for two weeks, demonstrating a dose-lowering advantage of at least tenfold. Furthermore, 10 mg kg-1 of 73-DY sustainably suppressed serum viral levels to undetectable levels for ≈ 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73-DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long-term immunotherapy with reverse chimeric 73-DY facilitated the restoration of anti-HBV immune responses. This study provides a foundation for the development of next-generation antibody-based CHB therapies.

Dietary Lactobacillus delbrueckii Affects Ileal Bacterial Composition and Circadian Rhythms in Pigs.

Intestinal bacteria, synchronized with diet and feeding time, exhibit circadian rhythms and anticipate host gut function; however the effect of dietary probiotics on gut bacterial diurnal rhythms remains obscure. In this study, bacteria were sequenced at 6 Zeitgeber times (ZT) from a pig model of ileal T-shaped fistula to test ileal bacterial composition and circadian rhythms after Lactobacillus delbrueckii administration. The results showed that dietary L. delbrueckii enhanced ileal bacterial α-diversity at Zeitgeber time (ZT) 16, evidenced by an increased Simpson index compared with control pigs. At the phylum level, Firmicutes was identified as the largest phyla represented in pigs, but dietary L. delbrueckii only increased the abundance of Tenericutes at ZT16. At the genus level, 11/100 genera (i.e., Lactobacillus, Enterococcus, Leptotrichia, Pediococcus, Bifidobacte, Cellulosilyticum, Desulfomicrobium, Sharpea, Eubacterium, Propionivibrio, and Aerococcus) were markedly differentiated in L. delbrueckii-fed pigs and the effect was rhythmicity-dependent. Meanwhile, dietary L. delbrueckii affected six pathways of bacterial functions, such as membrane transport, metabolism of cofactors and vitamins, cell motility, the endocrine system, signaling molecules and interaction, and the nervous system. Cosinor analysis was conducted to test bacterial circadian rhythm in pigs, while no significant circadian rhythm in bacterial α-diversity and phyla composition was observed. Lactobacillus, Terrisporobacter, and Weissella exhibited significant rhythmic fluctuation in the control pigs, which was disturbed by probiotic exposure. In addition, dietary L. delbrueckii affected circadian rhythms in ileal Romboutsia, Erysipelatoclostridium, Cellulosilyticum, and Eubacterium abundances. Dietary L. delbrueckii affected both ileal bacterial composition and circadian rhythms, which might further regulate gut function and host metabolism in pigs.

Effect of inactivated vaccine boosters against severe and critical COVID-19 during the Omicron BA.5 wave: A retrospective analysis of hospitalized patients in China.

Few real-world analyses of the ability of vaccines to protect against severe COVID-19 have been published. In this real-world study, we compared the prevalence of severe or critical COVID-19 between patients at our hospital who were not vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or who had been vaccinated partial, full, or booster course with the CoronaVac, containing inactivated virus propagated in Vero cells. Data from electronic health records were retrospectively analyzed for 4090 inpatients with COVID-19 who were treated at West China Hospital, Chengdu between December 6, 2022 and February 14, 2023. Clinicodemographic characteristics and COVID-19 severity were compared among patients who had been vaccinated 0, 1, 2 or more times with inactivated vaccine CoronaVac. To evaluate vaccine effectiveness over time, we plotted Kaplan-Meier curves with the percentage of patients with the outcome of severe or critical COVID-19 from the time of their last vaccine dose according to vaccination status. Ordinal logistic regression was used to assess associations between vaccination status and COVID-19 severity. Cox regression was used to identify risk factors for severe or critical COVID-19. Among the 4090 patients, 171 had been vaccinated partial and 423 twice with the full CoronaVac regimens, while 905 had been vaccinated three times (boosted). The prevalence of severe or critical COVID-19 among patients was 11 percentage points lower among those vaccinated (40%) at least twice than among those unvaccinated (51%) (p＜0.001), while it was 10% points lower among those who had received a booster (41%) than among those unvaccinated (51%) (p＜0.001). Protection against severe or critical COVID-19 due to vaccination was significantly weakened by being older than 65 years, being male, or having diabetes, chronic heart disease, autoimmune disease, or chronic lung disease. Completing a full course of immunization with inactivated vaccine CoronaVac against SARS-CoV-2 can reduce the risk of severe or critical COVID-19 due to the Omicron BA.5 subvariant.

Polyketides/nonribosomal peptides from Streptococcus mutans and their ecological roles in dental biofilm.

Streptococcus mutans is the major etiological agent of dental caries in humans. S. mutans overgrowth within dental biofilms can trigger biofilm dysbiosis, ultimately leading to the initiation or progression of dental caries. Polyketides and nonribosomal peptides (PKs/NRPs) are secondary metabolites with complex structures encoded by a cluster of biosynthetic genes. Although not essential for microbial growth, PKs/NRPs play important roles in physiological regulation. Three main classes of hybrid PKs/NRPs in S. mutans have been identified, including mutanobactin, mutanocyclin, and mutanofactin, encoded by the mub, muc, and muf gene clusters, respectively. These three hybrid PKs/NRPs play important roles in environmental adaptation, biofilm formation, and interspecies competition of S. mutans. In this review, we provide an overview of the major hybrid PKs/NRPs of S. mutans, including mutanobactin, mutanocyclin, and mutanofactin and address their ecological roles in dental biofilms. We place specific emphasis on important questions that are yet to be answered to provide novel insights into the cariogenic mechanism of S. mutans and facilitate improved management of dental caries. We highlight that S. mutans PKs/NRPs may be potential novel targets for the prevention and treatment of S. mutans-induced dental caries. The development of genomics, metabolomics, and mass spectrometry, together with the integration of various databases and bioinformatics tools, will allow the identification and synthesis of other secondary metabolites. Elucidating their physicochemical properties and their ecological roles in oral biofilms is crucial in the identification of novel targets for the ecological management of dental caries.

Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD.

Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

FoxO1 knockdown inhibits RANKL-induced osteoclastogenesis by blocking NLRP3 inflammasome activation.

OBJECTIVES: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. MATERIALS AND METHODS: A conventional ligature-induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA-seq) was performed to explore the underlying mechanisms of FoxO1 knockdown-mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation-related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA-seq revealed that the nuclear factor kappa B (NF-κB) and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1-knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. CONCLUSIONS: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF-κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment.

Applied anatomy of female pelvic plexus for nerve-sparing radical hysterectomy(NSRH).

BACKGROUND: Nerve-sparing radical hysterectomy(NSRH)has the advantage of reducing postoperative complications and improving postoperative quality of life. The separation and protection of the pelvic plexus in NSRH is extremely important and challenging. METHODS: 24 female cadaveric hemipelves were dissected. Morphologic patterns and compositions of pelvic plexus as well as relationship of pelvic plexus to the surrounding structures were observed and documented. RESULTS: Two patterns of superior hypogastric plexus were observed, including fenestrated and cord-like shape. The origin of bilateral hypogastric nerves were inferiorly to upper margin of promontory about 1.6 ± 0.1 cm and parallel to the ureter in front of the sacrum. Pelvic splanchnic nerves(PSN)from the second sacral nerve, the third sacral nerve and the forth sacral nerve were observed combing with the hypogastric nerves within the lateral rectal ligament. The sacral sympathetic trunk can be identified anteriorly or medially to the anterior sacral foramen. We identified the boundaries of pelvic plexus as following: the upper margin is formed by the PSNs from the third sacral nerve, posterior margin by inferior rectal artery, and anteriorly by vesical venous plexus. The uterine branches from pelvic plexus were observed accompanying with uterine artery, while other branches were inferiorly to the artery. The PSNs were located beneath the deep uterine veins within the cardinal ligament. The upper margin of pelvic plexus was observed directly approach to urinary bladder within the vesico-vaginal ligament as a single trunk accompanying with ureter, between the middle and inferior vesical veins. CONCLUSIONS: Our study clarified the intricate arrangement, distribution and relationship of female pelvic plexus and the related structures to provide reference index for NSRH application. The innervation patterns of bladder and uterine were clarified, and by tracing these visceral branches of pelvic plexus, we suggest several new important land markers for NSRH.

Emerging opportunities to treat idiopathic pulmonary fibrosis: Design, discovery, and optimizations of small-molecule drugs targeting fibrogenic pathways.

Idiopathic pulmonary fibrosis (IPF) is the most common fibrotic form of idiopathic diffuse lung disease. Due to limited treatment options, IPF patients suffer from poor survival. About ten years ago, Pirfenidone (Shionogi, 2008; InterMune, 2011) and Nintedanib (Boehringer Ingelheim, 2014) were approved, greatly changing the direction of IPF drug design. However, limited efficacy and side effects indicate that neither can reverse the process of IPF. With insights into the occurrence of IPF, novel targets and agents have been proposed, which have fundamentally changed the treatment of IPF. With the next-generation agents, targeting pro-fibrotic pathways in the epithelial-injury model offers a promising approach. Besides, several next-generation IPF drugs have entered phase II/III clinical trials with encouraging results. Due to the rising IPF treatment requirements, there is an urgent need to completely summarize the mechanisms, targets, problems, and drug design strategies over the past ten years. In this review, we summarize known mechanisms, target types, drug design, and novel technologies of IPF drug discovery, aiming to provide insights into the future development and clinical application of next-generation IPF drugs.

Anti-Epstein-Barr Virus BNLF2b for Mass Screening for Nasopharyngeal Cancer.

BACKGROUND: Population screening of asymptomatic persons with Epstein-Barr virus (EBV) DNA or antibodies has improved the diagnosis of nasopharyngeal carcinoma and survival among affected persons. However, the positive predictive value of current screening strategies is unsatisfactory even in areas where nasopharyngeal carcinoma is endemic. METHODS: We designed a peptide library representing highly ranked B-cell epitopes of EBV coding sequences to identify novel serologic biomarkers for nasopharyngeal carcinoma. After a retrospective case-control study, the performance of the novel biomarker anti-BNLF2b total antibody (P85-Ab) was validated through a large-scale prospective screening program and compared with that of the standard two-antibody-based screening method (EBV nuclear antigen 1 [EBNA1]-IgA and EBV-specific viral capsid antigen [VCA]-IgA). RESULTS: P85-Ab was the most promising biomarker for nasopharyngeal carcinoma screening, with high sensitivity (94.4%; 95% confidence interval [CI], 86.4 to 97.8) and specificity (99.6%; 95% CI, 97.8 to 99.9) in the retrospective case-control study. Among the 24,852 eligible participants in the prospective cohort, 47 cases of nasopharyngeal carcinoma (38 at an early stage) were identified. P85-Ab showed higher sensitivity than the two-antibody method (97.9% vs. 72.3%; ratio, 1.4 [95% CI, 1.1 to 1.6]), higher specificity (98.3% vs. 97.0%; ratio, 1.01 [95% CI, 1.01 to 1.02]), and a higher positive predictive value (10.0% vs. 4.3%; ratio, 2.3 [95% CI, 1.8 to 2.8]). The combination of P85-Ab and the two-antibody method markedly increased the positive predictive value to 44.6% (95% CI, 33.8 to 55.9), with sensitivity of 70.2% (95% CI, 56.0 to 81.4). CONCLUSIONS: Our results suggest that P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the standard two-antibody method. (Funded by the National Key Research and Development Program of China and others; ClinicalTrials.gov number, NCT04085900.).

Recent Advances in Fabrication of Durable, Transparent, and Superhydrophobic Surfaces.

Transparent superhydrophobic coatings have been extensively investigated due to their ability to provide self-cleaning properties for outdoor applications. However, the widespread implementation of these coatings on a large scale is impeded by the challenges of poor durability and complex fabrication procedures. In this review, the fundamentals and theories governing the mutually exclusive properties of superhydrophobicity, optical transparency, and susceptibility to wear are introduced, followed by a discussion of representative examples of advanced surface design and processing optimizations. Also, robust evaluation protocols for assessing mechanical and chemical stabilities are briefed and potential research directions are presented. This review can offer the research community a better understanding of durable and transparent superhydrophobic surfaces, thereby facilitating their development for real-world applications.

Artesunate ameliorates ligature-induced periodontitis by attenuating NLRP3 inflammasome-mediated osteoclastogenesis and enhancing osteogenic differentiation.

Periodontitis, arguably the greatest common infective chronic inflammatory disease, is characterized by an imbalance of the host immune system and excessive osteoclastogenesis activity with severe alveolar bone loss. Nevertheless, in consideration of the harmful effects of repeated treatment, more sensible intervention drugs for periodontitis need to be developed. Artesunate (ART), derived from Artemisia annua L., has shown remarkable pharmacokinetic and clinical value, as well as anti-inflammatory and immunomodulatory effects in various immune and chronic diseases due to its endoperoxide group. However, the role of ART in mediating periodontitis-induced alveolar bone resorption has not been examined. In this study, ART treatment effectively ameliorated ligature-induced periodontitis via attenuating osteoclast formation in a dose-dependent manner. Mechanistically, RNA-seq revealed that ART dramatically reduced the enrichment of NLRP3 inflammasome-related genes. Concordant with our study, MCC950, a specific inhibitor of NLRP3 inflammasome, also greatly restrained osteoclastogenesis, suggesting that ART suppressed osteoclast formation by blocking NLRP3 inflammasome activation. In addition to regulating osteoclastogenesis, ART significantly enhanced osteogenic differentiation by alleviating the expression of cytokines in inflammatory conditions. Our data shed light on the probably potential mechanism of ART treatment for the intervention of periodontitis.

Comparative study of pancreatic vessels and mesopancreas of rhesus monkeys and humans.

Introduction: With the introduction of the concept of mesopancreas defining the perineural structures that includes neurovascular bundle and lymph nodes extending from the posterior surface of the pancreatic head to behind the mesenteric vessels,Total Mesopancreas Excision (TMpE) based on this theory has facilitated the development of pancreatic cancer surgery in clinical practice in recent years. However, the existence of so called mesopancreas in the human body is still in debate and the comparative study of mesopancreas of rhesus monkey and human have not been well investigated. Purpose: The aim of our study is to compare the pancreatic vessels and fascia of human and rhesus monkeys in anatomical and embryological perspectives and to support the utilization of rhesus monkey as animal model. Methods: In this study, 20 rhesus monkey cadavers were dissected and their mesopancreas location, relationships and arterial distribution were analyzed. We compared the location and developmental patterns of mesopancreas in macaques and humans. Results: The results showed that the distribution of pancreatic arteries in rhesus monkeys was the same as that in humans, which is consistent with phylogenetic similarities. However, the morphological features of the mesopancreas and greater omentum is anatomically different from that of humans, including (1) the greater omentum is not connected to the transverse colon in monkeys. (2) The presence of the dorsal mesopancreas of the rhesus monkey suggests that it be an intraperitoneal organ. Comparative anatomical studies of mesopancreas and arteries in macaques and humans showed characteristic patterns of mesopancreas and similarities in pancreatic artery development in nonhuman primates, consistent with phylogenetic differentiation.

Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers.

Lung cancer in never-smokers (LCINS) presents clinicopathological and molecular features distinct from that in smokers. Tumor microenvironment (TME) plays important roles in cancer progression and therapeutic response. To decipher the difference in TME between never-smoker and smoker lung cancers, we conduct single-cell RNA sequencing on 165,753 cells from 22 treatment-naive lung adenocarcinoma (LUAD) patients. We find that the dysfunction of alveolar cells induced by cigarette smoking contributes more to the aggressiveness of smoker LUADs, while the immunosuppressive microenvironment exerts more effects on never-smoker LUADs' aggressiveness. Moreover, the SPP1hi pro macrophage is identified to be another independent source of monocyte-derived macrophage. Importantly, higher expression of immune checkpoint CD47 and lower expression of major histocompatibility complex (MHC)-I in cancer cells of never-smoker LUADs imply that CD47 may be a better immunotherapy target for LCINS. Therefore, this study reveals the difference of tumorigenesis between never-smoker and smoker LUADs and provides a potential immunotherapy strategy for LCINS.

Comparing T- and B-cell responses to COVID-19 vaccines across varied immune backgrounds.

The emergence of adapted variants of the SARS-CoV-2 virus has led to a surge in breakthrough infections worldwide. A recent analysis of immune responses in people who received inactivated vaccines has revealed that individuals with no prior infection have limited resistance to Omicron and its sub-lineages, while those with previous infections exhibit a significant amount of neutralizing antibodies and memory B cells. However, specific T-cell responses remain largely unaffected by the mutations, indicating that T-cell-mediated cellular immunity can still provide protection. Moreover, the administration of a third dose of vaccine has resulted in a marked increase in the spectrum and duration of neutralizing antibodies and memory B cells in vivo, which has enhanced resistance to emerging variants such as BA.2.75 and BA.2.12.1. These results highlight the need to consider booster immunization for previously infected individuals and the development of novel vaccination strategies. The rapid spread of adapted variants of the SARS-CoV-2 virus presents a significant challenge to global health. The findings from this study underscore the importance of tailoring vaccination strategies based on individual immune backgrounds and the potential need for booster shots to combat emerging variants. Continued research and development are crucial to discovering new immunization strategies that will effectively protect public health against the evolving virus.

Abnormally primed CD8 T cells: The Achilles' heel of CHB.

Chronic hepatitis B virus (HBV) infection continues to be a significant public health challenge, and more than 250 million people around world are infected with HBV. The clearance of HBV with virus-specific CD8 T cells is critical for a functional cure. However, naïve HBV-specific CD8 T cells are heavily hindered during the priming process, and this phenomenon is closely related to abnormal cell and signal interactions in the complex immune microenvironment. Here, we briefly summarize the recent progress in understanding the abnormal priming of HBV-specific CD8 T cells and some corresponding immunotherapies to facilitate their functional recovery, which provides a novel perspective for the design and development of immunotherapy for chronic HBV infection (CHB). Finally, we also highlight the balance between viral clearance and pathological liver injury induced by CD8 T-cell activation that should be carefully considered during drug development.

Ubiquitin-specific proteases: Vital regulatory molecules in bone and bone-related diseases.

Stabilization of bone structure and function involves multiple cell-to-cell and molecular interactions, in which the regulatory functions of post-translational modifications such as ubiquitination and deubiquitination shouldn't be underestimated. As the largest family of deubiquitinating enzymes, the ubiquitin-specific proteases (USPs) participate in the development of bone homeostasis and bone-related diseases through multiple classical osteogenic and osteolytic signaling pathways, such as BMP/TGF-ß pathway, NF-κB/p65 pathway, EGFR-MAPK pathway and Wnt/ß-catenin pathway. Meanwhile, USPs may also broadly regulate regulate hormone expression level, cell proliferation and differentiation, and may further influence bone homeostasis from gene fusion and nuclear translocation of transcription factors. The number of patients with bone-related diseases is currently enormous, making exploration of their pathogenesis and targeted therapy a hot topic. Pathological increases in the levels of inflammatory mediators such as IL-1ß and TNF-α lead to inflammatory bone diseases such as osteoarthritis, rheumatoid arthritis and periodontitis. While impaired body metabolism greatly increases the probability of osteoporosis. Abnormal physiological activity of bone-associated cells results in a variety of bone tumors. The regulatory role of USPs in bone-related disease has received particular attention from academics in recent studies. In this review, we focuse on the roles and mechanisms of USPs in bone homeostasis and bone-related diseases, with the expectation of informing targeted therapies in the clinic.

Environmental microcystin exposure triggers the poor prognosis of prostate cancer: Evidence from case-control, animal, and in vitro studies.

Microcystin-leucine-arginine (MC-LR) is positively linked with multiple cancers in humans. However, the association between MC-LR and the risk and prognosis of prostate cancer has not been conducted in epidemiological studies. No reported studies have linked MC-LR exposure to the poor prognosis of prostate cancer by conducting experimental studies. The content of MC-LR was detected in most of the aquatic food in wet markets and supermarkets in Nanjing and posed a health risk for consumers. MC-LR levels in both prostate cancer tissues and serum were significantly higher than controls. The adjusted odds ratio (OR) for prostate cancer risk by serum MC-LR was 1.75 (95%CI: 1.21-2.52) in the whole subjects, and a positive correlation between MC-LR and advanced tumor stage was observed. Survival curve analysis indicated patients with higher MC-LR levels in tissues exhibited poorer overall survival. Human, animal, and cell studies confirmed that MC-LR exposure increases the expression of estrogen receptor-α (ERα) and promotes epithelial-mesenchymal transition (EMT) in prostate cancer. Moreover, MC-LR-induced decreased E-cadherin levels, increased vimentin levels, and increased migratory and invasive capacities of prostate cancer cells were markedly suppressed upon ERα knockdown. MC-LR-induced xenograft tumor growth and lung metastasis in BALB/c nude mice can be effectively alleviated with ERα knockdown. Our data demonstrated that MC-LR upregulated vimentin and downregulated E-cadherin through activating ERα, promoting migration and invasion of prostate cancer cells. Our findings highlight the role of MC-LR in prostate cancer, providing new perspectives to understand MC-LR-induced prostatic toxicity.

A glycoengineered therapeutic anti-HBV antibody that allows increased HBsAg immunoclearance improves HBV suppression in vivo.

Introduction: The effective and persistent suppression of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection (CHB) is considered to be a promising approach to achieve a functional cure of hepatitis B. In our previous study, we found that the antibody E6F6 can clear HBsAg through FcγR-mediated phagocytosis, and its humanized form (huE6F6 antibody) is expected to be a new tool for the treatment of CHB. Previous studies have shown that the glycosylation of Fc segments affects the binding of antibodies to FcγR and thus affects the biological activity of antibodies in vivo. Methods: To further improve the therapeutic potential of huE6F6, in this study, we defucosylated huE6F6 (huE6F6-fuc-), preliminarily explored the developability of this molecule, and studied the therapeutic potential of this molecule and its underlying mechanism in vitro and in vivo models. Results: huE6F6-fuc- has desirable physicochemical properties. Compared with huE6F6-wt, huE6F6-fuc- administration resulted in a stronger viral clearance in vivo. Meanwhile, huE6F6-fuc- keep a similar neutralization activity and binding activity to huE6F6-wt in vitro. Immunological analyses suggested that huE6F6-fuc- exhibited enhanced binding to hCD32b and hCD16b, which mainly contributed to its enhanced therapeutic activity in vivo. Conclusions: In summary, the huE6F6-fuc- molecule that was developed in this study, which has desirable developability, can clear HBsAg more efficiently in vivo, providing a promising treatment for CHB patients. Our study provides new guidance for antibody engineering in other disease fields.

The Effect of Sanyrene Liquid Dressing in Preventing Radiation Dermatitis: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the efficacy of Sanyrene liquid dressing (Urgo Medical) in preventing radiation dermatitis (RD) among patients with cancer after radiotherapy. DATA SOURCES: The authors searched the China National Knowledge Infrastructure, SinoMed, WanFang Data, PubMed, Web of Science, EMBASE, and the Cochrane Library databases for articles published from inception to January 2021. STUDY SELECTION: The preliminary search identified 146 studies. After removing duplicates, applying exclusion criteria, and screening titles and abstracts, 19 studies met the inclusion criteria. DATA EXTRACTION: A standardized form was constructed to extract data from eligible studies. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. DATA SYNTHESIS: The authors identified a total of 19 studies involving 1,508 patients that assessed the effectiveness of Sanyrene liquid dressing in preventing RD in patients with cancer after radiotherapy. The findings suggested that Sanyrene decreases the total incidence of RD (odds ratio [OR], 5.00; 95% CI, 2.77-9.03; P < .00001), as well as the incidence of RD grade 2 (OR, 0.55; 95% CI, 0.36-0.85; P = .007), grade 3 (OR, 0.22; 95% CI, 0.09-0.57; P = .002), and grade 4 (OR, 0.32; 95% CI, 0.13-0.78; P = .01). In addition, in comparison with controls, Sanyrene liquid dressing improves the cure rate (OR, 8.18; 95% CI, 4.03-16.60; P < .00001) and delays the occurrence of RD (mean difference, 3.69; 95% CI, 3.03-4.36; P < .00001). CONCLUSIONS: Sanyrene liquid dressing can decrease both the total incidence of RD and the incidence of RD above grade 2. It also improves the cure rate and delays the occurrence of RD. Thus, Sanyrene may be a superior option for preventing RD after radiotherapy. However, the findings were assessed as moderate- to low-quality evidence and more high-quality trials are needed to support this result.