Most of the life forms on Earth have gradually evolved an endogenous biological clock under the long-term influence of periodic daily light-dark cycles. This biological clock system plays a crucial role in the orderly progression of life activities. In mammals, central circadian clock is located in the suprachiasmatic nucleus of the hypothalamus and the function of the biological clock relies on a transcription-translation negative feedback loop. As a negative regulator in this loop, the function of CHRONO is less known. To deeply explore the role of the Chrono gene in rhythm entrainment and physiology, we constructed a Chrono gene knockout mouse strain using the CRISPR/Cas9 technology and analyzed its entrainment ability under different T cycles. Running wheel tests and glucose tolerance tests were also performed. The results showed that the period of the endogenous biological clock of Chrono knockout mice was prolonged, and the entrainment rate under the T21 cycle was decreased. In addition, metabolic abnormalities, including weight gain and impaired glucose tolerance, were observed in the non-entrained mice. Overall, this study reveals a crucial role of the Chrono gene in maintaining circadian rhythms and metabolic balance, providing a new perspective for understanding the relationship between the biological clock and metabolism. Further research is needed to fully understand the underlying molecular mechanisms.
Animals ; Mice, Knockout ; Mice ; Circadian Rhythm/genetics* ; Metabolic Diseases/physiopathology* ; Photoperiod ; Male ; Period Circadian Proteins/physiology* ; Light ; Circadian Clocks/physiology*

OBJECTIVE: Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research. In this report, two distinguished phenotypic isolates (CJ1Z, flhA mutant strain, lawn; CJ2S, flhA complemented strain, normal colony) appeared during laboratory passages for NCTC11168. METHODS: Phenotypic assessments, including motility plates, transmission electron microscopy, biofilm formation assay, autoagglutination assay, and genome re-sequencing for these two isolates (CJ1Z, flhA mutant strain; CJ2S, flhA complemented strain) were carried out in this study. RESULTS: Transmission electron microscopy revealed that the flagellum was lost in CJ1Z. Phenotypic assessments and genome sequencing of the two isolates were performed in this study. The capacity for biofilm formation, colony auto-agglutination, and isolate motility was reduced in the mutant CJ1Z. Comparative genomic analysis indicated a unique native nucleotide insertion in flhA (nt, 2154) that caused the I719Y and I720Y mutations and early truncation in flhA. CONCLUSION FlhA has been found to influence the expression of flagella in C. jejuni. To the best of our knowledge, this is the first study to describe the function of the C-terminal of this protein.
Campylobacter jejuni/genetics* ; Bacterial Proteins/metabolism* ; Mutation ; Biological Variation, Population

Child ; Humans ; Rural Population ; China/epidemiology* ; Respiratory Tract Infections/prevention & control*

Objective: To study the changes in the permeability of the blood labyrinth barrier of the aging cochlea in mice, and to establish a non-contact co-culture model of endothelial cells (EC) and pericytes (PC) to furtherly investigate the cochlear stria vascularis microvascular pericytes impact on the permeability of endothelial cells. Methods: C57BL/6J mice were divided into two groups, three months old as young group, 12 months old as senile group. Cell experiment was divided into four groups, EC group, EC+PC co-culture group, D-gal+EC group and D-gal+EC+PC co-culture group. Auditory brainstem response (auditory brain response, ABR) was used to detect the auditory function of the two groups of mice. Evans blue staining was applied to detect the permeability of the cochlear blood labyrinth barrier of the two groups of mice. Transmission electron microscopy was used to observe the ultrastructure of blood labyrinth barrier endothelial cells, pericytes and tight junctions in the two groups of mice. Immunohistochemistry was used to detect the expression levels of tight junction proteins in the stria vascularis of the cochlea of the two groups of mice. Transwell chamber was used to detect the permeability of endothelial cells. Western blot and immunofluorescence technology were used to detect the expression level of tight junction protein on endothelial cells. SPSS 20.0 software was used to analyze the data. Results: Compared with the young group, the ABR threshold of the aging group was significantly increased, the latency of wave I was prolonged (t=10.25, P<0.01;t=5.61, P<0.05), the permeability of the cochlear blood labyrinth barrier was increased and the expression of tight junction protein on the vascular stria was decreased (P<0.05). The cochlear ultrastructure showed that the cochlear vascular stria microvascular lumen was deformed, the basement membrane thickened and the tight junction gap between endothelium enlarged. The positive rate of ECs and PCs in primary culture was more than 95%. The cells induced by 15 g/L D-gal were determined to be senescent cells. Compared with EC group, the expression of tight junction protein in endothelial cells of D-gal+EC group decreased（t=7.42，P<0.01；t=13.19，P<0.05）and the permeability increased (t=11.17, P<0.01). In the co-culture group, the expression of tight junction protein between endothelial cells in EC+PC co-culture group and D-gal+EC+PC co-culture group increased and the permeability decreased. Conclusions: In aging mice, the permeability of cochlear blood labyrinth barrier will increase and the level of tight junction protein will decrease; in aging state, cochlear vascular stria microvascular pericytes may affect endothelial cell permeability by regulating the expression of tight junction protein.
Animals ; Cochlea ; Endothelial Cells ; Mice ; Mice, Inbred C57BL ; Pericytes ; Permeability ; Stria Vascularis ; Tight Junctions

Consensus ; Critical Illness ; Humans ; Serum Albumin ; Serum Albumin, Human

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: To investigate the effect of a modified Wuzi Yanzong Pill (, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism. METHODS: Forty-five male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modified of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin (HE) staining. Tat-interactive protein, 60kD (Tip60) and p53 expressions were determined by Western blotting. RESULTS: The apoptosis index (AI) in the radiation group was higher than that of the WZYZP group and control group on day 1 (D1), day 7 (D7) day 14 (D14) after radiation (P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group (P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14 (P<0.05). CONCLUSION A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis.
Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Male ; Microwaves ; Rats, Wistar ; Testis ; drug effects ; metabolism ; pathology ; radiation effects ; Trans-Activators ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Objective To detect the expressions of hypoxia inducible factor-1α (HIF-1α) and aquaporin-1 (AQP1) in the alkali-burn cornea and investigate the roles of HIF-1α and AQP1 in alkali-burn mechanisms.Methods Totally 48 healthy adult female Kunming mice were selected,and the left eyes were treated with saline as the control group,and the model of corneal alkali burn was established with concentration of 1 mol · L-1 NaOH on the right eyes,and then these rats were randomly divided into 1-day,4-day,7-day and 14-day group.The expressions of HIF-1α and AQP1 in the cornea were detected using immunofluorescence and qRT-PCR after corneal alkali burn model was successful.Results In the control group,HIF-1 α was expressed in the corneal epithelial basement membrane,but it was increased in the corneal epithelium layer 1 day after alkali burn,and it was expressed in the corneal epithelium layer and stroma 4 days,and peaked 7 days after alkali burn;AQP1 was weakly expressed only in the endothelial layer in the control group,but it was increased in the corneal endothelial layer 1 day after alkali burn,and it was strongly expressed in the endothelial cell layer and the stroma 4 days and 7 days after alkali burn.qRT-PCR indicated that the relative expression level of HIF-1α mRNA was 269.70 ± 15.68 in 1-day group,350.50 ± 67.26 in 4-day group and 272.10 ±6.88 in 7-day group,respectively,which all were higher than that in the control group (188.70 ± 33.99),with significant difference (P ＜ 0.05).In addition,the relative expression level of AQP1 mRNA was 61.90 ± 5.45 in 1-day group and 48.34 ± 1.33 in 7-day group,which were significantly higher than that in the control group (36.43 ± 3.95),with statistical difference (P ＜ 0.05).Conclusion Alkali burn can cause the pathological changes in the cornea,and HIF-1 α and AQP1 involve in corneal injury after alkali burn.

BACKGROUNDFemale sexual dysfunction (FSD) is a highly prevalent and often underestimated problem. However, large-scale, population-based epidemiological surveys of FSD are scarce in China. The present study was conducted to evaluate the prevalence and the potential risk factors of FSD across a selection of social groups in Beijing, China, based on the Female Sexual Function Index (FSFI).

METHODSA cross-sectional study based on the multiple-stage cluster sampling was performed with adult women throughout the Dongcheng and Shunyi districts of Beijing. The Chinese version of FSFI was used, as well as questions on demographic characteristics, the disease-related context, and social relationships.

RESULTSA total of 6000 consecutive women entered this study, with an actual response from 5024 women, corresponding to a response rate of 83.7%. A total of 4697 (78.3%) questionnaires were effective. The prevalence of adult FSD in Beijing was 2973 (63.3%) using a score of 26.55 as the boundary value, whereas the total mean FSFI score was 23.92 ± 6.37. However, 1423 (30.3%) women did not seek help. By multivariate logistic regression analysis, the possible potential risk factors included age (odds ratio [OR] = 1.051), dissatisfaction with the spouse's sexual ability (OR = 3.520), poor marital affection (OR = 2.087), spouse sexual difficulties (OR = 1.720), dissatisfaction with married life (OR = 1.476), living in a rural area (OR = 1.292), chronic pelvic pain (OR = 1.261), chronic disease (OR = 1.534), previous pelvic surgery (OR = 1.605), vaginal delivery (OR = 2.285), lower education (OR = 3.449) and postmenopausal (OR = 3.183).

CONCLUSIONSAs suggested by the FSFI scores, female sexual problems are highly prevalent in Beijing. Dissatisfaction with the spouse's sexual ability, poor marital affection, sexual difficulties of the spouse, dissatisfaction with the marriage, rural life, CPP, and postmenopausal were conceivable risk factors for FSD in Beijing women.

OBJECTIVETo investigate the effects of human umbilical cord blood-derived mesenchymal stem cells(HUCMSC) on the leukemic cell line HL-60 and acute lymphoblastic leukemia cell line Jurkat as well as the role of CXCL12/CXCR4.

METHODSHL-60 cells and Jurkat cells were co-cultured with human umbilical cord blood mesenchymal stem cell (HUCMSC), and the model was treated with G-CSF, AMD3100 and their combination. The cell viability and cell cycle were measured by Cell Counting Kit-8 (CCK-8), the apoptosis and the cell-cycle analysis were assessed by flow cytometry with the Annexin V/PI double staining. The expression of surface CXCR4 protein and total CXCR4 protein of leukemic cells were detected by flow cytometry and Western blot respectively.

RESULTSHUCMSC could decrease the viability of HL-60 cells and Jurkat cells, as well as the percentage of apoptotic cells, they could also increase the number of G/Gcells, while G-CSF and AMD3100 could reduce the proliferation of HL-60 cells and Jurkat cells in HUCMSC co-culture model, destructed the anti-apoptotic effect of HUCMSC on HL-60 cells and Jurkat cells, and the combination of 2 drugs resulted in a synergistic effect. The G-CSF could reduce the expression of surface CXCR4 protein and total CXCR4 protein in leukemic cells, while AMD3100 could only decrease the expression of surface CXCR4 protein of leukemia cell membrane, having no effect on the expression of CXCR4 protein in cytoplasm.

CONCLUSIONHuman umbilical cord blood mesenchymal stem cells can inhibit the proliferation and apoptosis of acute leukemia cells and increase the number of G/Gphase cells in leukemic cells. The AMD3100 can decrease the expression of surface CXCR4 protein in leukemia cells, G-CSF can decrease expression of total CXCR4 protein as well as membrane CXCR4 protein. Both of them can block the CXCL12/CXCR4 signal axis, weakening the relationship between leukemia cells and microenvironment. And on the basic of HUCMSC influenced leukemia cells' growth and proliferation, the cell viability will be weakened, its apoptosis will be promoted, and the percentage of G/Gphase cells in leukemia cells will be decreased.