Effects of Parental Dietary Exposure to GM Rice TT51 on the Male Reproductive System of Rat Offspring

Objective To evaluate the health effects of parental dietary exposure to GM rice TT52 on the male reproductive system of rat offspring. Methods Rice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats （15 males/30 females each group） for 70 days prior mating and throughout pregnancy and lactation. After weaning, eight male offspring rats were randomly selected at each group and fed with diets correspondent to their parents＇ for 70 days. The effects of exposure to TT52 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serum hormones （FSH, LH, and testosterone levels）, testis histopathological examination, and the relative expression levels of selected genes along the hypothalamic-pituitary- testicular （HPT） axis. Results No significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis. Conclusion The results of this study demonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.

Sodium 4-phenylbutyrate Attenuates High-fat Diet-induced Impaired Spermatogenesis

Objective To determine the mitigating effects of sodium 4-phenylbutyrate(4-PBA) on high-fat diet(HFD)-induced spermatogenesis dysfunction. Methods Male rats(n = 30) were randomly divided into three groups: control, HFD, and 4-PBA(HFD +4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay. Results Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower(P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone(T), and reduced the rate of testicular cell apoptosis(P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats(P < 0.05). Conclusion HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD-induced impaired spermatogenesis via inhibition of apoptosis in rats. 4-PBA may have therapeutic value in the treatment of obesity-related impairment of spermatogenesis.

Intestinal natural killer/T-cell lymphoma presenting as a pancreatic head space-occupying lesion:A case report

BACKGROUND Intestinal natural killer/T-cell lymphoma(NKTCL)is a rare and aggressive non-Hodgkin’s lymphoma,and its occurrence is closely related to Epstein-Barr virus infection.In addition,the clinical symptoms of NKTCL are not obvious,and the specific pathogenesis is still uncertain.While NKTCL may occur in any segment of the intestinal tract,its distinct location in the periampullary region,which leads clinicians to consider mimics of a pancreatic head mass,should also be addressed.Therefore,there remain huge challenges in the diagnosis and treatment of intestinal NKTCL.CASE SUMMARY In this case,we introduce a male who presented to the clinic with edema of both lower limbs,accompanied by diarrhea,and abdominal pain.Endoscopic ultrasound(EUS)showed well-defined homogeneous hypoechoic lesions with abundant blood flow signals and compression signs in the head of the pancreas.Under the guidance of EUS-fine needle biopsy(FNB)with 19 gauge or 22 gauge needles,combined with multicolor flow cytometry immunophenotyping(MFCI)helped us diagnose NKTCL.During treatments,the patient was prescribed the steroid(dexamethasone),methotrexate,ifosfamide,L-asparaginase,and etoposide chemotherapy regimen.Unfortunately,he died of leukopenia and severe septic shock in a local hospital.CONCLUSION Clinicians should enhance their understanding of NKTCL.Some key factors,including EUS characteristics,the right choice of FNB needle,and combination with MFCI,are crucial for improving the diagnostic rate and reducing the misdiagnosis rate.

Distinct palmitoylation of Foxp3 regulates the function of regulatory T cells via palmitoyltransferases

Regulatory T cells(Tregs)play pivotal roles in maintaining immune homeostasis and preventing excessive immune responses in vivo.As key players in suppressing immune reactions,they help to preserve immune tolerance and are thus crucial for preventing autoimmune diseases.Within the tumor microenvironment(TME),Tregs facilitate tumor immune evasion by impairing the activity of effector cells via multiple mechanisms,thus contributing to the initiation and progression of tumors[1].To perform this regulatory function,Tregs depend on the master transcription factor forkhead box protein p3(Foxp3)[2].The expression of Foxp3 has emerged as indispensable for the development and optimal function of Tregs[3].Interestingly,different posttranslational modifications,including phosphorylation,ubiquitination,glycosylation,and acetylation,exert significant regulatory effects on the biological function of Foxp3[4-8].

Inhibition of METTL3 in macrophages provides protection against intestinal inflammation

Inflammatory bowel disease(IBD)is prevalent,and no satisfactory therapeutic options are available because the mechanisms underlying its development are poorly understood.In this study,we discovered that increased expression of methyltransferase-like 3(METTL3)in macrophages was correlated with the development of colitis and that depletion of METTL3 in macrophages protected mice against dextran sodium sulfate(DSS)-induced colitis.Mechanistic characterization indicated that METTL3 depletion increased the YTHDF3-mediated expression of phosphoglycolate phosphatase(PGP),which resulted in glucose metabolism reprogramming and the suppression of CD4+T helper 1(Th1)cell differentiation.Further analysis revealed that glucose metabolism contributed to the ability of METTL3 depletion to ameliorate colitis symptoms.In addition,we developed two potent small molecule METTL3 inhibitors,namely,F039-0002 and 7460-0250,that strongly ameliorated DSS-induced colitis.Overall,our study suggests that METTL3 plays crucial roles in the progression of colitis and highlights the potential of targeting METTL3 to attenuate intestinal inflammation for the treatment of colitis.

A dynamically evolving war between autophagy and pathogenic microorganisms

Autophagy is an intracellular degradation process that maintains cellular homeostasis.It is essential for protecting organisms from environmental stress.Autophagy can help the host to eliminate invading pathogens,including bacteria,viruses,fungi,and parasites.However,pathogens have evolved multiple strategies to interfere with autophagic signaling pathways or inhibit the fusion of autophagosomes with lysosomes to form autolysosomes.Moreover,host cell matrix degradation by different types of autophagy can be used for the proliferation and reproduction of pathogens.Thus,determining the roles and mechanisms of autophagy during pathogen infections will promote understanding of the mechanisms of pathogen-host interactions and provide new strategies for the treatment of infectious diseases.

Mitochondrial protein IF1 is a potential regulator of glucagon-like peptide(GLP-1) secretion function of the mouse intestine

IF1(ATPIF1) is a nuclear DNA-encoded mitochondrial protein whose activity is inhibition of the F1Fo-ATP synthase to control ATP production.IF1 activity remains unknown in the regulation of GLP-1 activity.In this study,IF1 was examined in the diet-induced obese mice using the gene knockout(If1-KO) mice.The mice gained more body weight on a high fat diet without a change in food intake.Insulin tolerance was impaired,but the oral glucose tolerance was improved through an increase in GLP-1 secretion.The KO mice exhibited an improved intestine structure,mitochondrial superstructure,enhanced mitophagy,reduced apoptosis and decreased adenine nucleotide translocase 2(ANT2) protein in the intestinal epithelial cells together with preserved gut microbiota.The data suggest that GLP-1 secretion was enhanced in the obese If1-KO mice to preserve glucose tolerance through a signaling pathway of ANT2/mitochondria/L-cells/GLP-1/insulin.IF1 is a potential mitochondrial target for induction of GLP-1 secretion in L-cells.

G3BP2 regulates oscillatory shear stress-induced endothelial dysfunction

GTPase-activating SH3 domain-binding protein 2(G3BP2)is a mediator that responds to environmental stresses through stress granule formation and is involved in the progression of chronic diseases.However,no studies have examined the contribution of G3BP2 in the oscillatory shear stress(OSS)-induced endothelial dysfunction.Here we assessed the effects of G3BP2 in endothelial cells(ECs)function and investigated the underlying mechanism.Using shear stress apparatus and partial ligation model,we identified that stress granulerelated genes in ECs could be induced by OSS with RNA-seq,and then confirmed that G3BP2 was highly and specifically expressed in athero-susceptible endothelia in the OSS regions.G3bp2e/eApoee/e mice had significantly decreased atherosclerotic lesions associated with deficiency of G3BP2 in protecting endothelial barrier function,decreasing monocyte adhesion to ECs and inhibiting the proinflammatory cytokine levels.Furthermore,loss of G3BP2 diminished OSS-induced inflammation in ECs by increasing YAP nucleocytoplasmic shuttling and phosphorylation.These data demonstrate that G3BP2 is a critical OSS regulated gene in regulating ECs function and that G3BP2 inhibition in ECs is a promising atheroprotective therapeutic strategy.

An inducible model for specific neutrophil depletion by diphtheria toxin in mice

Neutrophils are crucial for immunity and play important roles in inflammatory diseases;however,mouse models selectively deficient in neutrophils are limited,and neutrophil-specific diphtheria toxin(DT)-based depletion system has not yet been established.In this study,we generated a novel knock-in mouse model expressing diphtheria toxin receptor(DTR)under control of the endogenous Ly6G promoter.We showed that DTR expression was restricted to Ly6G+neutrophils and complete depletion of neutrophils could be achieved by DT treatment at 24-48 h intervals.We characterized the effects of specific neutrophil depletion in mice at steady-state,with acute inflammation and during tumor growth.Our study presents a valuable new tool to study the roles of neutrophils in the immune system and during tumor progression.

Bites from the same dog,different outcomes for two patients:a case report

Background:Rabies is a serious reemerging zoonosis in China.At present human rabies cases are primarily diagnosed based on clinical presentation.Case presentation:In August 2012,a woman and her son were attacked by a stray dog in Henan,China.The son received rabies postexposure prophylaxis(wound treatment followed by vaccine,no immunoglobulin),however,the mother did not.Rabies infection was subsequently laboratory confirmed in the mother and she died in December;her son is alive and healthy after 2 years of follow-up.Conclusion:This report documents that the timely utilization of postexposure prophylaxis is a required measure in preventing rabies after exposure to an animal bite.

Effects of cisplatin in combination with hyperthermia on biological characteristics of retroperitoneal liposarcoma

Pathologically,retroperitoneal liposarcoma(RPLS)is a group of malignant tumors,which originates from adipose tissue in retroperitoneal space,accounting for almost 70%of all retroperitoneal tumors.RPLS has no optimal treatment.Surgical resection(R_(0)/R_(1))is the most effective therapy;however,recurrence rate is very high.Grossly incomplete surgical resection(R_(2))is an important risk factor for early recurrence of RPLS.

Human β-defensin-2 Enhances Anti-tumor Efficacy of Survivin-based Broad-spectrum DNA Vaccine in Mouse Tumor Model

Objective:Malignant tumors greatly endanger and affect the quality of human life.Among antitumor biotherapy strategies,DNA vaccines hold promise in part because of their unique advantages.In this study,an effective broad-spectrum antitumor DNA vaccine expressing human survivin T34A dominant-negative mutant fused with humanβ-defensin-2(HBD2)was investigated.Methods:The expression profiles of genes of interest were examined using western blotting,reverse transcription-polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay(ELISA)in vitro.The immune function of the fusion gene vaccine(FGV)was assessed in BALB/c mice,which included detection of serum antibody,spleen lymphocyte proliferation,interferon-gamma(IFN-γ)secretion,and lactate dehydrogenase(LDH)release.In vivo antitumor effects of FGV were examined in a mouse breast cancer(4T1)model,whereas in vitro effects were assessed using tumor cells derived from different origins.Caspase-3activity in tumor cells was also assessed after vaccine transfection.Results:The FGV triggered humoral as well as cellular immune responses against survivin.It exhibited more potent inhibition of tumor growth as well as prolonged the survival of immunized mice compared to mice immunized with only either survivin T34A or HBD2 vaccines.In addition,FGV displayed stronger cytotoxicity against tumor cells derived from different origins compared to the other vaccines and facilitated increased caspase-3 activity in transfected tumor cells.Conclusion:The novel DNA vaccine consisting of a fusion of the universal tumor antigen survivin T34A mutant with molecular adjuvant HBD2generates enhanced broad-spectrum antitumor efficacy against cancers derived from various origins.

Two human monoclonal SARS-CoV-2 antibodies that maintain neutralizing potency against the SARS-CoV-2 Omicron BA.1 and BA.2 variants

The pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to sweep the globe with devastating consequences on human lives and world economy.As an RNA virus,SARS-CoV-2 has a relatively high mutation rate and is rapidly evolving.Thus,new SARS-CoV-2 variants continued to emerge,5 of which were designated by the World Health Organization(WHO)as variants of concern(VOCs),Alpha(B.1.1.7).

A self-assembling prodrug nanosystem to enhance metabolic stability and anticancer activity of gemcitabine

Self-assembly is a powerful approach in molecular engineering for biomedical applications,in particu-lar for creating self-assembling prodrugs.Here,we report a self-assembling prodrug of the anticancer drug gemcitabine(Gem)based on amphiphilic dendrimer approach.The prodrug reported in this study demonstrates high drug loading(40%)and robust ability to self-assemble into small nanomicelles,which increase the metabolic stability of Gem and enable entry into cells via endocytosis,hence bypassing transport-mediated uptake.In addition,this prodrug nanosystem exhibited an effective pH-and enzyme-responsive release of Gem,resulting in enhanced anticancer activity and reduced toxicity.Harboring ad-vantageous features of both prodrug-and nanotechnology-based drug delivery,this self-assembling Gem prodrug nanosystem constitutes a promising anticancer candidate.This study also offers new perspectives of the amphiphilic dendrimer nanoplatforms for the development of self-assembling prodrugs.