Modeling and anti-sway control method for vertical lift-up/lay-down process of slender-beam payload.

The existing crane control methods mainly aim at suppressing the oscillation of the payloads during the transportation process. However, during the vertical lift-up/lay-down process of the slender-beam payload (SBP), such as the installation of the wind turbine towers, rocket assembly, and pipeline laying, one end of the SBP is lifted up and the other end is in contact with the ground. In this situation, the external disturbance may cause the SBP to sway around the contact point. In this paper, a nonlinear three-dimensional dynamic model for the vertical lift-up/lay-down process of the SBP is established. On this basis, a control method for suppressing oscillation during the lift-up/lay-down process of the SBP is proposed by adopting the non-singular terminal sliding mode control (NTSMC). The stability of the NTSMC is proved based on the Lyapunov method. Simulations and experiments are carried out to verify the effectiveness of the proposed method.

An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants.

The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome editing. However, natural nucleases of this system often exhibit low efficiency, limiting their application. Here, we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease, Cas12i3. As a result, we developed Cas-SF01, a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian cells. Cas-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 nucleases. Compared to natural Cas12i3, Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN PAMs. In addition, we identified an amino acid substitution, D876R, that markedly reduced the off-target effect while maintaining high on-target activity, leading to the development of Cas-SF01HiFi (high-fidelity Cas-SF01). Finally, we show that Cas-SF01 has high gene editing activities in mice and plants. Our results suggest that Cas-SF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.

Effect of electroacupuncture on ventricular structure and function in rats with myocardial ischemia-reperfusion injury. / ç”µé’ˆå¯¹å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ å¿ƒå®¤ç»“æž„å’ŒåŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on changes of ventricular structure and function in rats with myocardial ischemia-reperfusion injury (MIRI), so as to explore its potential mechanisms underlying improvement of ventricular remodeling after MIRI. METHODS: Forty male SD rats were randomly divided into 4 groups：sham operation group, model group, EA group and medication (sacubactril valsartan, LCZ696) group, with 10 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery and reperfusion. EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once every other day for 21 d. Rats of the medication group received gavage of LCZ696 (60 mg·kg-1·d-1). After the intervention, echocardiography was used to detect the ejection fraction (EF) and fractional shortening (FS) of the left ventricle, and the contents of serum tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1) and intercellular cell adhesion molecule-1(ICAM-1) were assayed by enzyme-linked immunosorbent assay. The pathological changes of myocardial tissue were observed after HE staining. The Masson staining was used to evaluate the myocardial collagen deposition and myocardial fibrosis. The mRNA expression levels of collagen Ⅰ and Ⅲ and connective tissue growth factor (CTGF) in the myocardial tissue were detected by quantitative real-time PCR, and the expression levels of IL-1ß and IL-18 were detected by Western blot. RESULTS: In contrast to the sham operation group, the EF and FS levels of the left ventricle were ob-viously decreased (P<0.001), while the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, the expression levels of IL-1ß and IL-18 were significantly increased (P<0.001, P<0.000 1, P<0.05, P<0.01) in the model group. Compared with the model group, the EF and FS levels were remarkably increased (P<0.01), whereas the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, and the expression levels of IL-1ß and IL-18 were significantly down-regulated (P<0.001, P<0.01, P<0.05) in both the medication and EA groups. No significant differences were found between the EA and medication groups in all the indexes mentioned above. CONCLUSIONS: EA can improve the left-ventricular fibrosis and function, delay or reverse ventricular remodeling in MIRI rats, which may be related to its functions in down-regulating myocardial inflammatory response and mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF.

A study on mental health and its influencing factors among police officers during the COVID-19 epidemic in China.

Background: The outbreak of the COVID-19 pandemic has had a tremendous impact on people's health and well-being. The crisis also threw into sharp relief the fact that police officers faced an increased risk of developing mental health problems. The main purpose of this study was to explore the effects of work stress and risk perception on the mental health of police officers during the epidemic. Methods: We conducted a cross-sectional online survey among police officers in Wuhan city, China, and data were collected from 11 March to 12 May 2022. A total of 358 questionnaires were received, of which 302 were considered valid. The questionnaires included demographic information, work stress scale, Symptom Checklist 90 (SCL-90) and epidemic risk perception scale. Descriptive analyses, one-way analysis of variance and linear regression were used to analyze the data. Results: The prevalence of mental health problems was 38.74% among the surveyed police officers. The results indicated that the total score of SCL-90 and its subdimensions were positively correlated with work stress and risk perception. Moreover, we found that three factors were relevant to the police's mental health: age, marital status, and education. Conclusion: Front-line police officers tend to show a higher prevalence of symptoms of mental disorders during the COVID-19 pandemic. We found that increased work stress and risk perception may adversely affect police officers' mental health. Consequently, policy-makers and police organizations should establish an internal mental health problem coping team to improve police officers' mental health resilience.

[Effect of electroacupuncture combined with intradermal needling on simple obesity and serum intestinal lymphatic function-related factors].

OBJECTIVE: To assess the efficacy of the combined treatment with electroacupuncture (EA) and intradermal needling on simple obesity and explore its underlying effect mechanism. METHODS: A total number of 116 patients with simple obesity were randomized into an observation group (58 cases, 3 cases dropped off and 2 cases removed) and a control group (58 cases, 4 cases dropped off and 1 cases removed). Patients in the control group received EA at Zhongwan (CV 12), Quchi (LI 11), Zusanli (ST 36), Pishu (BL 20), Weishu (BL 21), etc., for 30 min each time. On the base of the intervention as the control group, the patients in the observation group received the intradermal needling at Tianshu (ST 25), Daheng (SP 15), Zusanli (ST 36), Shangjuxu (ST 37), Quchi (LI 11), Pishu (BL 20) and Weishu (BL 21). In each group, the intervention was given once every two days, 3 times a week, consecutively for 3 months. Before and after treatment, the obesity indexes (body mass [BW], body mass index [BMI], body fat percentage [F%], adiposity [A] and waist circumference [WC]), the serum intestinal lymphatic function-related factors (vascular endothelial growth factor C [VEGF-C], delta-like ligand 4 [DLL4], adrenomedullin [ADM]), blood lipid (total cholesterol [TC], triglyceride [TG] and low density lipoprotein-cholesterol [LDL-C]), and fasting plasma glucose (FPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were observed in the patients of both groups; and the efficacy was assessed. RESULTS: The effective rate was 88.7% (47/53) in the observation group, higher than 71.7% (38/53) in the control group (P<0.05). After treatment, except FPG in the control group, BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, as well as TC, TG, LDL-C, FBG, FINS and HOMA-IR were all reduced compared with those before treatment in both groups (P<0.05). The reduction ranges of BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, and TC, LDL-C, FINS and HOMA-IR in the observation group were all larger than those in the control group (P<0.05). CONCLUSION: Electroacupuncture combined with intradermal needling can reduce body weight and lipid, and improve insulin resistance in treatment of simple obesity, which is achieved probably through inhibiting lymphangiogenesis and promoting lymphatic endothelial permeability.

Inhibition of acylglycerol kinase sensitizes DLBCL to venetoclax via upregulation of FOXO1-mediated BCL-2 expression.

Background: Despite of the paradigm change on the treatments of acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) by venetoclax, it has been less successful in the treatment of diffuse large B-cell lymphoma (DLBCL). Here, we explored whether acylglycerol kinase regulates the sensitivity of DLBCLs to venetoclax and its mechanism in both cell lines and preclinical animal models. Methods: The expression of AGK and sensitivity to venetoclax of seven DLBCL cell lines were determined. Upon knockdown and overexpression of AGK by lentivirus in DLBCL cells, the venetoclax-induced apoptosis and PTEN-FOXO1-BCL-2 signaling axis were evaluated in vitro. The efficacy of venetoclax and PTEN-FOXO1-BCL-2 signaling axis were evaluated in immunodeficient NCG mice that were implanted with control or shAGK stably transduced SU-DHL4 cells. The expressions of AGK, BCL-2 and FOXO1 were evaluated in tumor tissues of DLBCL patients. Results: AGK expression was inversely correlated with sensitivity of DLBCL to venetoclax. Inhibition of AGK rendered the DLBCL cells more sensitive to venetoclax. Mechanistically, AGK phosphorylated and inactivated PTEN, which led to AKT activation and reduced FOXO1 nuclear translocation. Inhibition of AGK also led to enhanced efficacy of venetoclax for suppression of DLBCL tumor growth in vivo, which was dependent on FOXO1. In human DLBCL tumor tissues, the expression of AGK inversely correlated with BCL-2 expression, as well as the amounts of nuclear FOXO1. Conclusions: Our data demonstrated that AGK regulates venetoclax response in DLBCL via PTEN-FOXO1-BCL-2 signaling axis. Targeting AGK may enhance the efficacy of venetoclax for the treatment of DLBCL patients.

Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.

T regulatory (Treg) cells are essential for self-tolerance whereas they are detrimental for dampening the host anti-tumor immunity. How Treg cells adapt to environmental signals to orchestrate their homeostasis and functions remains poorly understood. Here, we identified that transcription factor EB (TFEB) is induced by host nutrition deprivation or interleukin (IL)-2 in CD4+ T cells. The loss of TFEB in Treg cells leads to reduced Treg accumulation and impaired Treg function in mouse models of cancer and autoimmune disease. TFEB intrinsically regulates genes involved in Treg cell differentiation and mitochondria function while it suppresses expression of proinflammatory cytokines independently of its established roles in autophagy. This coordinated action is required for mitochondria integrity and appropriate lipid metabolism in Treg cells. These findings identify TFEB as a critical regulator for orchestrating Treg generation and function, which may contribute to the adaptive responses of T cells to local environmental cues.

Effects of resveratrol treatment on quality and antioxidant properties of postharvest strawberry fruit.

Strawberry fruit is one of people's favorite fruits. It has high nutritional value and health care effects. Strawberries lose their edible value quickly after being picked because of their thin skin, which is easily damaged. In order to find a method to maintain the quality of strawberries, the effects of resveratrol treatment on the nutritional quality and antioxidant metabolism of strawberry fruit were studied. The result indicated that 100 µM resveratrol was the optimal concentration to delay the occurrence of decay. Strawberry fruit treated with resveratrol delayed the decrease in firmness, total soluble solids (TSS), total phenolics content (TPC), total flavonoid content (TFC), vitamin C (Vc) content,1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbezothi- azot-hiazoline-6-sulfonic acid) (ABTS) radical scavenging capacities. The malondialdehyde (MDA) content, hydrogen peroxide (H2 O2 ) content, and superoxide anion (O2 •- ) production of control fruit were significantly higher than those of treated fruit. Strawberry fruit treated with resveratrol also increased the activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) during storage. Therefore, resveratrol has been proved to effectively improve the nutritional quality and antioxidant properties of strawberry fruit. PRACTICAL APPLICATIONS: Strawberry fruit is rich in nutrients, which is beneficial to human health. But strawberry fruit has high water content and soft tissue, which is easy to be damaged and decayed. Therefore, it is particularly important to find a way to maintain strawberry fruit quality. In this study, resveratrol has good antioxidant, health care, and antibacterial properties. Resveratrol treatment can maintain the nutritional quality of strawberry fruit and can be used as an effective method for strawberry fruit preservation.

Linker histone variant HIS1-3 and WRKY1 oppositely regulate salt stress tolerance in Arabidopsis.

The salt overly sensitive (SOS) pathway plays an important role in plant salt stress; however, the transcriptional regulation of the genes in this pathway is unclear. In this study, we found that Linker histone variant HIS1-3 and WRKY1 oppositely regulate the salt stress response in Arabidopsis (Arabidopsis thaliana) through the transcriptional regulation of SOS genes. The expression of HIS1-3 was inhibited by salt stress, and the disruption of HIS1-3 resulted in enhanced salt tolerance. Conversely, the expression of WRKY1 was induced by salt stress, and the loss of WRKY1 function led to increased salt sensitivity. The expression of SOS1, SOS2, and SOS3 was repressed and induced by HIS1-3 and WRKY1, respectively, and HIS1-3 regulated the expression of SOS1 and SOS3 by occupying the WRKY1 binding sites on their promoters. Moreover, WRKY1 and HIS1-3 acted upstream of the SOS pathway. Together, our results indicate that HIS1-3 and WRKY1 oppositely modulate salt tolerance in Arabidopsis through transcriptional regulation of SOS genes.

Bispecific antibody targeting TROP2xCD3 suppresses tumor growth of triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo. METHODS: The binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells. RESULTS: We demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model. CONCLUSION: This study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients.

AtWRKY1 negatively regulates the response of Arabidopsis thaliana to Pst. DC3000.

WRKY transcription factors (TFs) play a major role in resistance to plant diseases, but the role of AtWRKY1 in response to Pst. DC3000 is not clear. In this study, we found that AtWRKY1 negatively affected the response of Arabidopsis to Pst. DC3000. During Pst. DC3000 infection, the transcription of AtWRKY1 was suppressed. The wrky1 mutants displayed enhanced resistance to Pst. DC3000. In contrast, the overexpression of AtWRKY1 reduced the resistance. The relative RNA levels of defense related PR genes were increased in the loss-of-function mutants, whereas their expressions were decreased in the AtWRKY1-overexpressing plants. Further research revealed that salicylic acid (SA) can repress the expression of AtWRKY1, and overexpression of AtWRKY1 weakened the SA-mediated defense response. In addition, the AtWRKY1 protein can bind to the PR1 promoter in vivo and in yeast cells directly, thereby inhibiting the transcription of PR1. AtWRKY1 indirectly represses the expression of PR2 and PR5. Our results indicated that the AtWRKY1 gene negatively regulates the plant defense responses to Pst. DC3000 through SA signaling pathways.

Analgesic Effect of Electroacupuncture on Postherpetic Neuralgia: A Trial Protocol for a Multicenter Randomized Controlled Trial.

INTRODUCTION: The chronic neuropathic pain associated with postherpetic neuralgia (PHN) can last for several months or even many years, seriously affecting the affected person's work, sleep, mood, and daily life activities. In generaly, current treatments for PHN are at best limited and unsatisfactory, and adverse reactions are common, especially in elderly patients. Electroacupuncture (EA) is widely used clinically to manage painful diseases, but there remains a lack of evidence to support the effectiveness of EA on PHN. This study is designed to assess the efficacy and safety of EA on PHN, and to provide evidence-based medical evidence for EA treatment of PHN. METHODS: This multicenter, prospective, randomized controlled trial will recruit 448 patients with PHN at seven clinical centers. Multicenter stratified variable block randomization will be used, and the eligible patients will be randomly allocated in a ratio of 1:1 to the EA group or sham EA group. The EA group will receive 4 weeks of EA treatment, given as 30-min treatment sessions, once daily, 5 times per week, for a total of 20 treatments; the sham EA group will receive sham EA treatment under the same conditions. PLANNED OUTCOMES: The primary outcome measure is the 11-point Numeric Rating Scale pain score at week 4. The secondary outcome measures, including mechanical pain threshold, pain area of PHN, average number of pain episodes, the short-form McGill Pain Questionnaire 2, Zoster Brief Pain Inventory, the Depression, Anxiety, and Positive Outlook Scale, Patient Global Impression of Change, safety of EA, and use of concomitant medications, among others. The primary analysis of the outcomes will be the mixed-effect model with repeated measurement between groups on an intent-to-treat population. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04560361. Registered 23 September 2020 ( https://clinicaltrials.gov/ct2/show/NCT04560361?term=NCT04560361&draw=2&rank=1 ).

DAPK1 (death associated protein kinase 1) mediates mTORC1 activation and antiviral activities in CD8+ T cells.

Mechanistic target of rapamycin complex 1 (mTORC1) regulates CD8+ T-cell differentiation and function. Despite the links between PI3K-AKT and mTORC1 activation in CD8+ T cells, the molecular mechanism underlying mTORC1 activation remains unclear. Here, we show that both the kinase activity and the death domain of DAPK1 are required for maximal mTOR activation and CD8+ T-cell function. We found that TCR-induced activation of calcineurin activates DAPK1, which subsequently interacts with TSC2 via its death domain and phosphorylates TSC2 to mediate mTORC1 activation. Furthermore, both the kinase domain and death domain of DAPK1 are required for CD8+ T-cell antiviral responses in an LCMV infection model. Together, our data reveal a novel mechanism of mTORC1 activation that mediates optimal CD8+ T-cell function and antiviral activity.

Death-associated protein kinase 1 (DAPK1) controls CD8+ T cell activation, trafficking, and antitumor activity.

Appropriate migration of cytotoxic T effector cells into the tumors is crucial for their antitumor function. Despite the controversial role of PI3K-Akt in CD8+ T cell mTORC1 activation, a link between Akt-mTORC1 signaling and CD8+ trafficking has been demonstrated. We have recently discovered that TCR-induced calcineurin activates DAPK1, which interacts with TSC2 via its death domain and phosphorylates TSC2 via its kinase domain to mediate mTORC1 activation in CD8+ T cells. However, whether DAPK1 regulates CD8+ trafficking into tumors remains unclear. Here, using pharmacological inhibitor and genetic approaches, we found that like rapamycin, inhibition of DAPK1 activity led to enhanced expression of the homing receptors CD62L and CCR7. Deletion of either kinase domain or death domain in the T cell compartment reduced the T cell activation and maintained the expression of CD62L and CCR7. DAPK1-DD-deficient mice were more susceptible to tumor growth and deficiency of DAPK1 activity significantly reduced the migratory ability of CD8+ into the tumors. These data revealed a crucial role of DAPK1-mTORC1 in mediating CD8+ trafficking and antitumor function.

Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients.

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.

TFEB Mediates Immune Evasion and Resistance to mTOR Inhibition of Renal Cell Carcinoma via Induction of PD-L1.

PURPOSE: Despite the FDA approval of mTOR inhibitors (mTORi) for the treatment of renal cell carcinoma (RCC), the benefits are relatively modest and the few responders usually develop resistance. We investigated whether the resistance to mTORi is due to upregulation of PD-L1 and the underlying molecular mechanism. EXPERIMENTAL DESIGN: The effects of transcription factor EB (TFEB) on RCC proliferation, apoptosis, and migration were evaluated. Correlation of TFEB with PD-L1 expression, as well as effects of mTOR inhibition on TFEB and PD-L1 expression, was assessed in human primary clear cell RCCs. The regulation of TFEB on PD-L1 was assessed by chromatin immunoprecipitation and luciferase reporter assay. The therapeutic efficacies of mTORi plus PD-L1 blockade were evaluated in a mouse model. The function of tumor-infiltrating CD8+ T cells was analyzed by flow cytometry. RESULTS: TFEB did not affect tumor cell proliferation, apoptosis, and migration. We found a positive correlation between TFEB and PD-L1 expression in RCC tumor tissues, primary tumor cells, and RCC cells. TFEB bound to PD-L1 promoter in RCCs and inhibition of mTOR led to enhanced TFEB nuclear translocation and PD-L1 expression. Simultaneous inhibition of mTOR and blockade of PD-L1 enhanced CD8+ cytolytic function and tumor suppression in a xenografted mouse model of RCC. CONCLUSIONS: These data revealed that TFEB mediates resistance to mTOR inhibition via induction of PD-L1 in human primary RCC tumors, RCC cells, and murine xenograft model. Our data provide a strong rationale to target mTOR and PD-L1 jointly as a novel immunotherapeutic approach for RCC treatment.

Regulation of T cell differentiation and function by epigenetic modification enzymes.

Peripheral naive CD4+ and CD8+ cells are developed in the thymus and proliferate and differentiate into various specialized T cell subsets upon activation by peptide-major histocompatibility complexes in periphery to execute different functions during immune responses. Cytokines, transcription factors, and a large number of intracellular molecules have been shown to affect T cell development, activation, and function. In addition, epigenetic modifications, such as histone modification and DNA methylation, regulate T cell biology. The epigenetic modifications are regulated by a range of DNA methyltransferases, DNA demethylation enzymes, and histone modification enzymes. Dysregulations of epigenetic modifications are closely associated with autoimmune diseases and tumorigenesis. Here, we review the current literature about the functions of DNA and histone modification enzymes in T cell development, activation, differentiation, and function.

Alpha-lactose reverses liver injury via blockade of Tim-3-mediated CD8 apoptosis in sepsis.

In sepsis, the liver plays a crucial role in regulating immune responses and is also a target organ for immune-related injury. Despite the critical function of CD8+ T cells against opportunistic viral infections, the CD8 immune response in the liver during sepsis remains elusive. Here we found that Tim-3 is highly up-regulated in liver CD8+ T cells in a mouse cecal ligation and puncture model and in peripheral blood CD8+ T cells of human patients with sepsis. The expression of Tim-3 in liver CD8+ T cells displayed a bi-phasic pattern and deletion of Tim-3 led to reduction of CD8+ T cell apoptosis. Administration of α-lactose, a molecule with a similar structure to galactin-9, reduced Tim-3 expression and liver injury in sepsis. Our results demonstrate that targeting Tim-3 to boost CD8+ T cell immune response may offer an improved outcome in patients with sepsis.

Triglyceride accumulation inhibitory effects of new chromone glycosides from Drynaria fortunei.

Two new chromone glycosides, drynachromosides C (1) and D (2), along with five known chromones (3-7), were isolated from the rhizomes of Drynaria fortunei. The structures of the two new compounds were elucidated on the basis of physico-chemical property and spectroscopic data. Triglyceride (TG) accumulation inhibitory effects of the obtained chromones on 3T3-L1 cells were investigated. The results showed that 1, 2 and 5 exhibited inhibitory activity on TG accumulation. Effects of compounds 1 and 2 on mRNA expression of PPARγ, C/EBPα and aP2 in 3T3-L1 cells were also investigated.

Bacterial analysis of combined periodontal-endodontic lesions by polymerase chain reaction-denaturing gradient gel electrophoresis.

We used denaturing gradient gel electrophoresis (DGGE) to compare bacterial profiles in periodontium and root canals of teeth with combined periodontal-endodontic lesions. Samples of dental plaque and necrotic pulp were collected from thirteen extracted teeth with advanced periodontitis. Genomic DNA was extracted for polymerase chain reaction (PCR) analysis using universal bacterial primers. The PCR products were then loaded onto DGGE gels to obtain fractionated bands. Characteristic DGGE bands were excised and DNA was cloned and sequenced. The number of bands, which indicates the number of bacterial species, was compared between dental plaques and necrotic pulp tissues from the same tooth. Although the difference was statistically significant (P < 0.01), there was no positive correlation; similarity (Dice coefficient) was 13.1% to 62.5%. Some bacteria species were present in both the periodontal pockets and root canals of the same tooth; however, periodontal bacteria did not always invade the root canals, and some bacteria in root canals were not present in periodontal pockets of the same tooth. In some teeth, unique bacteria in root canals had not passed from periodontal pockets. A basic local alignment search tool (BLAST) sequence search in Genbank indicated that new bacteria species were present in periodontal pockets and root canals. Their characteristics must thus be further analyzed.