Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective: To investigate the level of health literacy among residents in Karamay City, Xinjiang Uygur Autonomous Region, so as to provide insights into formulating health promotion strategies. Methods: Based on the Health Literacy Surveillance Program in Karamay City, demographic information and health literacy data were collected from residents aged 15 to 69 years in Karamay City in 2022, and levels of health literacy was analyzed. Factors affecting health literacy were identified using a multivariable logistic regression model. Results: A total of 1 473 respondents were included, with a mean age of (39.62±15.09) years. There were 751 men (50.98%) and 722 women (49.02%). The level of health literacy was 28.31%, and the prevalence rates of basic healthy knowledge and attitudes, healthy lifestyles and behaviors and basic health-related skills were 39.31%, 27.36% and 30.75%, respectively. The prevalence rates of safety and first aid, scientific health outlook, health information, chronic disease prevention, infectious disease prevention and basic medical care were 58.93%, 49.29%, 48.88%, 33.67%, 29.74% and 27.77%, respectively. Multivariable logistic regression analysis identified age (45 to 54 years OR=2.329, 95%CI: 1.005-5.398), ethnicity (ethnic minority, OR=0.459, 95%CI: 0.341-0.617), educational level (primary school and below, OR=0.213, 95%CI: 0.102-0.444; junior high school, OR=0.302, 95%CI: 0.193-0.471; high school, OR=0.579, 95%CI: 0.428-0.784), and annual household income (less than 10 000 Yuan, OR=0.352, 95%CI: 0.199-0.624; 10 000 to 30 000 Yuan, OR=0.447, 95%CI: 0.279-0.717; 30 000 to 50 000 Yuan, OR=0.598, 95%CI: 0.407-0.880) as factors affecting health literacy among residents in Karamay City. Conclusion The level of health literacy was 28.31% among residents in Karamay City in 2022. Health education and promotion should be carried out targeting residents of different ages, ethnicities, educational levels and annual household income, in order to further enhance the level of health literacy among residents in Karamay City.

Objective To investigate the antigen presentation characteristics of dendritic cells(DC)and B cells in cardiac grafts.Methods The heart of BALB/c mice was transplanted into the abdominal cavity of C57BL/6J mice.CD45+cells in the heart graft were extracted and sorted by flow cytometry at postoperative 5 d,and single cell RNA sequencing was performed.Taking DC and B cell subsets in cardiac grafts as the main study cells,the changing trend,antigen presenting ability and intercellular communication with T cells after heart transplantation were analyzed by bioinformatics analysis and flow cytometry.Gene ontology(GO)function enrichment difference analysis was adopted to prove the specific function and the reliability annotation of cell subsets.Results Germinal center-like B cell(GC-L B)was the B cell subset with the largest increase in quantity during the acute rejection phase,accounting for 87％.Classical DC(cDC)2 was the only DC subset with a significant increase in quantity during acute rejection of heart transplantation,accounting for 44％of DC subset,and it occupied the highest communication intensity with T cells after heart transplantation.Mononucleated DC(moDC)and memory B cell(MBC)were the main transmitters of T cell input signals in non-transplanted hearts,whereas transformed into cDC2 and GC-L B during the acute rejection phase.Among them,MBC and GC-L B were the main sources of T cell input signals in non-transplanted hearts and heart grafts.Conclusions Compared with DC,B cells occupy a higher number and weight in the intercellular communication with T cells in non-transplanted hearts and heart grafts,prompting that the antigen presenting activity of B cells is more active and stronger than DC in the early stage of acute rejection of heart transplantation.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily. As an amplifier of the inflammatory response, TREM-1 is mainly involved in the production of inflammatory mediators and the regulation of cell survival. TREM-1 has been studied in infectious diseases and more recently in non-infectious disorders. More and more studies have shown that TREM-1 plays an important pathogenic role in kidney diseases. There is evidence that TREM-1 can not only be used as a biomarker for diagnosis of disease but also as a potential therapeutic target to guide the development of novel therapeutic agents for kidney disease. This review summarized molecular biology of TREM-1 and its signaling pathways as well as immune response in the progress of acute kidney injury, renal fibrosis, diabetic nephropathy, immune nephropathy, and renal cell carcinoma.

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

OBJECTIVE: To investigate the repair method of type Ⅱc injury in the lateral meniscus popliteal tendon area based on the porcine knee joint. METHODS: Eighteen commercially available fresh porcine knee joints were randomly divided into 3 groups ( n=6). After preparing a type Ⅱc injury in the lateral meniscus popliteal tendon area, and the anterior (group A), posterior (group B), or anterior and posterior (group C) of the popliteal hiatus (PH) was sutured by vertical mattress. The tension meter was used to apply gradient tensions of 2, 4, 6, 8, and 10 N along the tibial plateau horizontally, respectively, to pull the midpoint of the lateral meniscus popliteal tendon area. The displacement values before modeling, after modeling, and after suture were recorded. The reduction value of lateral meniscus displacement and reduction rate after suture were calculated and compared between groups. RESULTS: There was no significant difference between groups ( P>0.05) in the displacement values before modeling, after modeling, and after suture under different tensions. There was no significant difference between groups A and C ( P>0.05) in the reduction value of lateral meniscus displacement and reduction rate after suture under different tensions. The reduction value of lateral meniscus displacement and reduction rate after suture in group B were lower than those in groups A and C. The reduction value of lateral meniscus displacement under tension of 2 N and the reduction rates under tensions of 2, 4, and 6 N between groups A and B showed significant differences ( P<0.05). The reduction value of lateral meniscus displacement and the reduction rate under tensions of 2, 4, and 6 N between groups B and C showed significant differences ( P<0.05). CONCLUSION Suturing the anterior area of PH is the key to repairing type Ⅱc injury of lateral meniscus popliteal tendon area.
Animals ; Humans ; Knee ; Knee Joint ; Menisci, Tibial/surgery* ; Swine ; Tendons ; Tibia

Objective:To evaluate the effect of dexmedetomidine on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in lung tissues in a rat model of cardiopulmonary bypass (CPB).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, weighing 320-350 g, aged 12-16 weeks, were randomly divided into sham operation group (group S), CBP group, and dexmedetomidine group (group Dex), with 8 rats in each group.In group Dex, dexmedetomidine was intravenously infused in a dose of 5 μg/kg starting from 15 min before CPB followed by infusion of 5 μg·kg -1·h -1 during CPB.Blood samples were collected at 2 h after the end of CPB for blood gas analysis, and oxygenation index (OI) and respiratory index (RI) were calculated.Then the rats were sacrificed by bloodletting.The lung tissues were removed for microscopic examination of the pathological changes which were scored and for determination of wet/dry weight ratio (W/D ratio), contents of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)(by enzyme-linked immunosorbent assay), and expression of JAK2, STAT3, phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) (by Western blot). The p-JAK2/JAK2 and p-STAT3/STAT3 ratios were calculated. Results:Compared with group S, the lung injury score, W/D ratio and RI were significantly increased, OI was decreased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were increased in the other two groups ( P<0.05). Compared with group CPB, the lung injury score, W/D ratio and RI were significantly decreased, OI was increased, the contents of TNF-α and IL-6, p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were decreased in group Dex ( P<0.05). Conclusion:The mechanism by which dexmedetomidine attenuates CPB-induced lung injury may be related to inhibiting JAK2/STAT3 signaling pathway and reducing inflammatory responses in lung tissues of rats.

Objective: To evaluate the efficacy of transcutaneous electrical acupoint stimulation (TEAS) for general anesthesia preserving spontaneous breathing in the patients undergoing thoracoscopic surgery. Methods: Forty patients of both sexes, aged 18-67 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with Mallampati physical status Ⅰ or Ⅱ, scheduled for elective thoracoscopic lobectomy, were divided into 2 groups (n=20 each) using a random number table method: general anesthesia preserving spontaneous breathing group (group GS) and TEAS plus general anesthesia preserving spontaneous breathing group (group TE+ GS). Anesthesia was routinely induced and maintained, a laryngeal mask was placed, and patients kept spontaneous breathing in two groups.The bispectral index value was maintained at 45-60.Patient-controlled intravenous analgesia was used after operation, and visual analogue scale score was maintained<4 points.In group TE+ GS, Xinshu and Feishu acupoints ipsilateral to the operated side and bilateral Hegu and Neiguan acupoints were stimulated with a disperse-dense wave, frequency 2/100 Hz and intensity 5-15 mA starting from 30 min before anesthesia induction until the end of surgery.The mean arterial pressure (MAP), heart rate (HR) and respiratory rate (RR) were recorded before induction of anesthesia, immediately after start of operation, during thoracic exploration, immediate after lobectomy , and at 30 min and 1 h after lobectomy.The intraoperative MAP, HR, and RR were recorded when clinically significant events occurred in two groups.Central venous blood samples were simultaneously collected for determination of concentrations of cortisol, norepinephrine, epinephrine, and blood glucose in serum (by enzyme-linked immunosorbent assay). The highest value of P_ETCO₂, the lowest value of SpO₂, and consumption of anesthetic drugs were recorded.Duration of post-anesthesia care unit stay, time to first flatus, ambulation time, occurrence of nausea and vomiting, chest tube drainage time, development of surgical complications, length of postoperative hospital stay and hospitalization expenses were recorded. Results: MAP, HR and RR all fluctuated within the normal range, and no clinically significant events occurred in two groups.Compared with group GS, the highest value of P_ETCO₂ was significantly decreased, the lowest value of SpO₂ was increased, the MAP and HR were decreased, the consumption of propofol and remifentanil was decreased, the cortisol, norepinephrine, epinephrine, and blood glucose concentrations in serum were decreased, the time to first flatus, ambulation time, chest tube drainage time and length of postoperative hospital stay were shortened, and the incidence of nausea and vomiting and hospitalization expenses were decreased in group TE+ GS (P<0.05). Conclusion TEAS can reduce the amount of opioids consumed in the perioperative period, effectively inhibits intraoperative stress responses, and is helpful in improving the early outcomes when used for general anesthesia preserving spontaneous breathing in the patients undergoing thoracoscopic surgery.

Objective To prepare hyaluronic acid(HA) targeted chlorogenic acid(HA-CA) liposome and to investigate its inhibition effect on HA receptor(CD44) high expressing A549 cells and HA receptor(CD44) low expression HepG2 cells proliferation.Methods HA-DOPE was synthesized;HA-CA liposome was prepared by thin membrane disperse method and the particle size was measured by using the dynamic light scattering particle size analyzer;the HPLC method was adopted to establish the CA in vitro contents measurement method and detect the HA-CA liposome entrapment efficiency;MTT assay was applied to detect the proliferation inhibiting effect of free CA,CA liposome and HA-CA liposome on A549 cells and HepG2 cells;the fluorescence cell uptake assay was adopted to verify the targeting effect of HA liposome.Results The average particle size of HA-CA was 219.20 nm and PDI was 0.16;the entrapment efficiency of HA-CA liposome was(85.36 ± 1.01)％;the proliferation inhibition effect of HA-CA liposome on A549 cells was significantly greater than that of CA liposome,moreover CA liposomewas greater than free CA,the proliferation inhibition effect of CA liposome and HA-CA liposome on HepG2 cells was basically similar,which was greater than that of free CA;the uptake of A549 cells on HA liposome carrying 6-coumarin(HA-C liposome) was higher than that of HepG2.Conclusion HA-CA liposome can specifically combined with the high expression HA receptor cells to achieve the active targeting effect of tumor cells.