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Abstract Background Florfenicol is a derivative of chloramphenicol that is used only for the treatment of animal diseases. A key resistance gene for florfenicol, floR, can spread among bacteria of the same and different species or genera through horizontal gene transfer. To analyze the potential transmission of resistance genes between animal and human pathogens, we investigated floR in Klebsiella pneumoniae isolates from patient samples. floR in human pathogens may originate from animal pathogens and would reflect the risk to human health of using antimicrobial agents in animals. Methods PCR was used to identify floR-positive strains. The floR genes were cloned, and the minimum inhibitory concentrations (MICs) were determined to assess the relative resistance levels of the genes and strains. Sequencing and comparative genomics methods were used to analyze floR gene-related sequence structure as well as the molecular mechanism of resistance dissemination. Results Of the strains evaluated, 20.42% (67/328) were resistant to florfenicol, and 86.96% (20/23) of the floR-positive strains demonstrated high resistance to florfenicol with MICs ≥512 μg/mL. Conjugation experiments showed that transferrable plasmids carried the floR gene in three isolates. Sequencing analysis of a plasmid approximately 125 kb in size (pKP18–125) indicated that the floR gene was flanked by multiple copies of mobile genetic elements. Comparative genomics analysis of a 9-kb transposon-like fragment of pKP18–125 showed that an approximately 2-kb sequence encoding lysR-floR-virD2 was conserved in the majority (79.01%, 83/105) of floR sequences collected from NCBI nucleotide database. Interestingly, the most similar sequence was a 7-kb fragment of plasmid pEC012 from an Escherichia coli strain isolated from a chicken. Conclusions Identified on a transferable plasmid in the human pathogen K. pneumoniae, the floR gene may be disseminated through horizontal gene transfer from animal pathogens. Studies on the molecular mechanism of resistance gene dissemination in different bacterial species of animal origin could provide useful information for preventing or controlling the spread of resistance between animal and human pathogens.

Abstract CD73, a cell surface-bound nucleotidase, serves as a crucial metabolic and immune checkpoint. Several studies have shown that CD73 is widely expressed on immune cells and plays a critical role in immune escape, cell adhesion and migration as a costimulatory molecule for T cells and a factor in adenosine production. However, recent studies have revealed that the protumour effects of CD73 are not limited to merely inhibiting the antitumour immune response. Nicotinamide adenine dinucleotide (NAD+) is a vital bioactive molecule in organisms that plays essential regulatory roles in diverse biological processes within tumours. Accumulating evidence has demonstrated that CD73 is involved in the transport and metabolism of NAD, thereby regulating tumour biological processes to promote growth and proliferation. This review provides a holistic view of CD73-regulated NAD + metabolism as a complex network and further highlights the emerging roles of CD73 as a novel target for cancer therapies.

Abstract The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization. The multifaceted effects and the relatively favorable side-effect profile of SGLT2 inhibitors render them a promising therapeutic candidate for cognitive disorders. Nonetheless, the application of SGLT2 inhibitors for cognitive impairment is not without its limitations, necessitating more comprehensive research to fully determine their therapeutic potential for cognitive treatment. In this review, we discuss the role of SGLT2 in neural function, elucidate the diabetes-cognition nexus, and synthesize current knowledge on the cognitive effects of SGLT2 inhibitors based on animal studies and clinical evidence. Research gaps are proposed to spur further investigation.

Abstract The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.

Abstract Background The triglyceride glucose (TyG) index, a metric for estimating insulin resistance (IR), is linked with cardiovascular disease (CVD) morbidity and mortality among the population regardless of diabetic status. However, IR prevalence and the association between the TyG index and heart failure (HF) in Americans is unclear. Methods The Nation Health and Nutrition Examination Survey (NHANES) (2009–2018) dataset was used. IR was defined by homeostatic model assessment of insulin resistance (HOMA-IR) > 2.0 and 1.5. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. A weighted logistic regression was applied to evaluate the association between the TyG index and the prevalence of HF. Results This study comprised 12,388 people, including 322 (2.6%) individuals with HF. The average prevalence of IR was found to be 13.9% and 22.7% for cutoff values greater than 2.0 and 1.5, respectively. HOMA-IR and the TyG index showed a moderate correlation (r = 0.30). There is a significant positive association between the TyG index and HF prevalence (per 1-unit increment; adjusted OR [aOR]: 1.34; 95% confidence interval [CI]: 1.02–1.76). Patients with higher TyG values were associated with a prevalence of HF (OR:1.41; 95% CI: 1.01,1.95) (quartiles 4 vs 1–3). The TyG index is associated with a higher prevalence of dyslipidemia, coronary heart disease, and hypertension but not a stroke (cerebrovascular disease). Conclusions Our results show that IR does not considerably increase from 2008 to 2018 in American adults. A moderate correlation is noted between HOMA-IR and the TyG index. TyG index is associated with the prevalence of HF, as were other cardiovascular diseases.

Abstract Background Whether routine lymph node dissection for early endometrial cancer is beneficial to survival is still controversial. However, surgeons usually perform lymph node dissection on all patients with early endometrial cancer. This study aimed to prove that the risk of lymph node metastasis, as defined by our standard, is very low in such patients and may change the current surgical practice. Methods 36 consecutive patients who had staged surgery for endometrial cancer were collected. All eligible patients meet the following very low risk criteria for lymph node metastasis, including: (1) preoperative diagnosis of endometrial cancer (preoperative pathological diagnosis), (2) tumors confined to the uterine cavity and not beyond the uterine body, (3) PET-MRI lymph node metastasis test is negative. PET-MRI and pathological examination were used to assess the extent and size of the tumor, the degree of muscular invasion, and lymph node metastasis. Results The median age at diagnosis was 52 years (range 35–72 years). The median tumor size on PET-MRI was 2.82 cm (range 0.66–6.37 cm). Six patients underwent robotic surgery, 20 underwent laparoscopic surgery, 8 underwent Laparoscopic-assisted vaginal hysterectomy, and 2 underwent vaginal hysterectomy. 23% (63.9%) patients had high-grade (i.e. 2 and 3) tumors. Among the 36 patients who underwent lymph node sampling, the median number of lymph nodes retrieved was 32 (range 9–57 nodules). No patient (0%) was diagnosed with lymph node metastasis. According to the policy of each institution, 8 patients (22.2%) received adjuvant therapy, and half of them also received chemotherapy (4 patients; 50%). Conclusions None of the patients who met the criteria had a pathological assessment of lymph node metastasis. Omitting lymph node dissection may be reasonable for patients who meet our criteria.