The systemic inflammation response index as a risk factor for hepatic fibrosis and long-term mortality among individuals with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: The systemic inflammation response index (SIRI) is associated with various diseases with inflammatory components, but its relationship with the progression of hepatic fibrosis and survival outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study was designed to investigate the potential associations between the SIRI and advanced hepatic fibrosis (AHF) as well as between the SIRI and long-term outcomes in individuals with MASLD. METHODS AND RESULTS: A prospective cohort study was conducted using data gathered from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2016. Weighted binary logistic regression, the Cox proportional hazards model, and time-dependent receiver operating characteristic (ROC) analyses were employed to assess the relationships among the SIRI, AHF, and mortality in patients with MASLD. Our study included a total of 5126 patients with MASLD. A higher SIRI was significantly associated with increased odds of AHF (OR 1.55, 95% CI 1.22, 1.96). According to the survival analyses, a higher SIRI was associated with greater all-cause (HR 1.19, 95% CI 1.15, 1.22) and cardiovascular mortality (HR 1.25, 95% CI 1.19, 1.32) after adjustment. The time-dependent ROC analysis indicated that the SIRI had a modest predictive value for discriminating MASLD individuals at higher versus lower mortality risk over 3-year, 5-year, and 10-year follow-up. CONCLUSIONS: The SIRI is a promising tool for identifying MASLD individuals at risk of progressing to AHF and for predicting mortality outcomes.

Robust Synthesis of GO-PtNPs Nanocomposites: A Highly Selective Colorimetric Sensor for Mercury Ion (II) Detection.

Due to their high toxicity and ongoing bioaccumulation, mercury ions (Hg2+) can cause significant harm to both the environment and human health. Therefore, rapid, accurate, and selective methods for Hg2+ detection are highly desirable. Herein, we present a simple method for depositing platinum nanoparticles (PtNPs) on graphene oxide (GO) to obtain graphene oxide-PtNPs (GO-PtNPs). The fabricated GO-PtNPs exhibit excellent peroxidase-like activity and high stability. Further, the GO-PtNPs nanozymes preferentially reduced Hg2+, thereby inhibiting the catalytic activity. By monitoring the color change in the chromogenic substrate, Hg2+ can be detected within 15 min. With a detection limit of 88.3 pM, the GO-PtNPs system may be employed to detect Hg2+ in a linear range of 0.1 nM to 10 µM. The simplicity and low cost of the proposed approach as well as its applicability to complicated samples demonstrate its capacity for mercury sensing in environmental samples.

Diagnostic value of anti-mitochondrial antibody in patients with primary biliary cholangitis: A systemic review and meta-analysis.

BACKGROUND: Anti-mitochondrial antibodies (AMA) and the M2 subtype are considered serological hallmarks in the diagnosis of primary biliary cholangitis (PBC). However, these autoantibodies may be undetectable in some patients. This meta-analysis aimed to evaluate the diagnostic accuracy of serum AMA and M2 for PBC. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) were calculated using a random-effects model. We also constructed hierarchical summary receiver operating characteristic curves and calculated the area under the curve values. RESULTS: Our meta-analysis included 28 studies, of which 24 examined the diagnostic accuracy of AMA for PBC. Pooled sensitivity and specificity of AMA were 84% (95% confidence intervals [CI] 77-90%) and 98% (96-99%), respectively. Pooled LR+, LR-, and DOR were 42.2 (22.1-80.5), 0.16 (0.11-0.24), and 262 (114-601), respectively. Sixteen studies explored the diagnostic value of the M2 subtype, demonstrating pooled sensitivity and specificity of 89% (81-94%) and 96% (93-98%), respectively. Pooled LR+, LR-, and DOR were 20.3 (8.0-51.1), 0.12 (0.05-0.26), and 169 (41-706), respectively. The hierarchical summary receiver operating characteristic curves for both of serum AMA and M2 subtype lie closer to the upper left corner of the plot with area under the curve values of 0.98 (95% CI = 0.96-0.99) and 0.98 (95% CI = 0.96-0.99) respectively. CONCLUSION: This meta-analysis provides evidence affirming the utility of AMA and M2 as sensitive and specific serological hallmarks that can facilitate early screening and diagnosis of PBC.

Analysis of risk factors for non-fusion of bone graft in anterior cervical discectomy and fusion: A clinical retrospective study.

BACKGROUND: Bone graft fusion is a major concern among surgeons after Anterior Cervical Discectomy and Fusion (ACDF) surgery as non-fusion may lead to further physical and drug therapies. METHODS: The related risk elements of non-fusion of bone graft in ACDF surgery were retrospectively assessed. Patients receiving ACDF operation in our hospital from January 2015 to December 2019 were retrospectively analyzed. According to the criteria, 107 study subjects were recruited with a total of 164 surgical segments. The general information of patients, bone graft materials, imaging parameters, and clinical efficacy was recorded. T-test, chi-square test and binary logistic regression evaluation were employed to explore the risk factors of bone graft nonunion. RESULTS: Low housefield unit (HU) value, diabetes, allogeneic bone, and hydroxyapatite (HA) artificial bone could be risk factors for bone graft fusion in ACDF surgery. Further multivariate analysis was performed and confirmed those related factors of bone graft non-fusion including low HU value (non-fusion rate: 32.53% [27/83], OR = 5.024, p = 0.025), diabetes (non-fusion rate: 53.33% [8/15], OR = 4.776, p = 0.031), allogeneic bone (18.57% [13/70], OR = 3.964, p = 0.046), and artificial bone (68.29% [28/41], OR = 50.550, p < 0.01). CONCLUSION: By looking at bone graft fusion, selecting autologous iliac bone is an ideal selection to avoid non-fusion of bone graft in ACDF. Diabetes was more important predictor of bone graft nonunion than low HU value. Larger sample size and longer follow-up are required to further confirm these findings in the future.

Heterologous expression of the Leymus chinensis metallothionein gene LcMT3 confers enhanced tolerance to salt stress in Escherichia coli, yeast, and Arabidopsis thaliana.

Salinity is poisonous to various plant physiological processes and poses an increasingly severe threat to agricultural productivity worldwide. As a tactic to mitigate this issue, the hunt for salt-tolerance genes and pathways is intensifying. The low-molecular-weight proteins known as metallothioneins (MTs) can effectively reduce salt toxicity in plants. In seeking concrete evidence of its function under salt stress conditions, a unique salt-responsive metallothionein gene, LcMT3, was isolated from the extremely salt-enduring Leymus chinensis and heterologously characterized in Escherichia coli (E. coli), yeast (Saccharomyces cerevisiae), as well as Arabidopsis thaliana. Overexpression of LcMT3 imparted resistance to salt in E. coli cells and yeast, while the development of control cells was completely inhibited. Besides, transgenic plants expressing LcMT3 exhibited significantly enhanced salinity tolerance. They had higher germination rates and longer roots than their nontransgenic counterparts during NaCl tolerance. For several physiological indices of salt tolerance, transgenic lines reduced the accumulation of malondialdehyde (MDA), relative conductivity, and reactive oxygen species (ROS) in comparison to nontransgenic Arabidopsis. They also possessed increased concentrations of proline (Pro), relative water content, chlorophyll content, coupled with three more active antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)). Transgenic plants also accumulated less Na+ and maintained a lower Na+/K+ ratio than control, which can be attributable to the transgene's regulatory effect on transporter proteins such as salt overly sensitive (SOS) and Na+/H+ antiporter (NHX1), as demonstrated by qPCR experiments. Collectively, LcMT3 could have a vital function in salinity resistance and be an essential candidate protein for abiotic stress.

Three Molecular Modification Strategies to Improve the Thermostability of Xylanase XynA from Streptomyces rameus L2001.

Glycoside hydrolase family 11 (GH11) xylanases are the preferred candidates for the production of functional oligosaccharides. However, the low thermostability of natural GH11 xylanases limits their industrial applications. In this study, we investigated the following three strategies to modify the thermostability of xylanase XynA from Streptomyces rameus L2001 mutation to reduce surface entropy, intramolecular disulfide bond construction, and molecular cyclization. Changes in the thermostability of XynA mutants were analyzed using molecular simulations. All mutants showed improved thermostability and catalytic efficiency compared with XynA, except for molecular cyclization. The residual activities of high-entropy amino acid-replacement mutants Q24A and K104A increased from 18.70% to more than 41.23% when kept at 65 °C for 30 min. The catalytic efficiencies of Q24A and K143A increased to 129.99 and 92.26 mL/s/mg, respectively, compared with XynA (62.97 mL/s/mg) when using beechwood xylan as the substrate. The mutant enzyme with disulfide bonds formed between Val3 and Thr30 increased the t1/260 °C by 13.33-fold and the catalytic efficiency by 1.80-fold compared with the wild-type XynA. The high thermostabilities and hydrolytic activities of XynA mutants will be useful for enzymatic production of functional xylo-oligosaccharides.

Improved thermostability, acid tolerance as well as catalytic efficiency of Streptomyces rameus L2001 GH11 xylanase by N-terminal replacement.

The N-terminal of xylanase from 11 family of glycoside hydrolases (GH11 xylanase) has an important effect on its thermostability and catalytic properties. Previous studies have unearthed five important residues located in the N-terminal and successfully improved the thermostability of several GH11 xylanases using amino acid substitutions. In the present study, we applied this tactic to construct a mutant of XynA from Streptomyces rameus L2001, XynAR, and studied its biochemical, catalytic and hydrolytic properties. The results showed that thermostability, acid tolerance as well as catalytic efficiency of XynAR significantly improved compared to those of XynA, while the hydrolytic characteristics changed. Computer simulation analysis showed that this tactic created new hydrogen bonds and electrostatic interactions in the N-terminal, resulting in decrease in the flexibility of N-terminal and surface electrostatic potential as well as a change in the profile of hydrogen bonds between the subsites and substrate in the cleft region of xylanase. This study showed that amino acid substitutions at the key sites of the N-terminal of GH11 xylanase can improve its thermostability and catalytic properties.

The Flow-Clutch Scale: Translation and validation study of the Chinese version.

PURPOSE: The integrated model of flow and clutch provides a multistate perspective to the optimal experiences during physical exercises. Based on this model, the Flow-Clutch Scale (FCS) was developed. The current study is the first step to test the psychometric properties of a Chinese version of the FCS (FCS-C). METHOD: A confirmatory factor analysis (CFA) with Maximum Likelihood estimate was performed in Chinese athletes (N = 426) to explore the structural validity of the FCS-C . The Pearson correlations between the subscales of the FCS-C and "non-reactivity to inner experiences", "cognitive flexibility", and "self-consciousness" were explored to examine the concurrent validity. Cronbach's alpha coefficients were used to assess the internal consistency of the total scale and subscales. Moreover, the test-retest reliability was examined in a subsample (N = 53) using a two-week interval. RESULTS: The results of CFA suggested that the three-factor model showed an acceptable model fit (χ2 = 459.40, df = 120, CFI = 0.95, GFI = 0.90, SRMR = 0.03, RMSEA = 0.082 [90% CI = 0.074-0.09]). Concerning the correlations between the factor "characteristics of flow" and "self-consciousness", the concurrent validity was not satisfactory. Moreover, the test-retest coefficients ranged from 0.75 to 0.78 (p < .01) and Cronbach's alpha ranged from 0.87 to 0.96. CONCLUSION: Results indicated that the three-factor model of FCS-C is acceptable, whereas its validity is not satisfactory to appropriately examine flow and/or clutch states in Chinese athletes. In summary, the current translation and validation study of the FCS-C allows for future research on optimal exercise experiences in Chinese-speaking cohorts including a further cultural adaptation of the questionnaire.

Emerging starch composite nanofibrous films for food packaging: Facile construction, hydrophobic property, and antibacterial activity enhancement.

Polymers synthesized from green resources have many advantages in food packaging and hence their development is very important. Herein, starch/polyvinyl alcohol (PVA) nanofibrous composite films were fabricated by electrospinning technology. Steam-induced cross-linking reaction with glutaraldehyde (GTA) and silver sodium zirconium phosphate (Ag-ZrP) was employed to improve the hydrophobic and antibacterial properties of the constructed nanofibrous films, respectively. The effects of starch/PVA ratio on the micro-morphology and mechanical properties of the binary composite film were investigated. The composite film showed optimal uniformity, bead-free electrospun nanofibers, with enhanced mechanical strength for the 60/40 (v/v) starch/PVA composite. Moreover, the crystallinity of PVA was reduced during the electrospinning process, whereas the introduction of PVA strengthened the hydrogen interactions and improved the thermal stability of the composite films. After the cross-linking with GTA, the starch/PVA films became more hydrophobic. Furthermore, the starch/PVA films embedded with Ag-ZrP had outstanding antibacterial property against both Gram-negative and Gram-positive bacteria. This work demonstrated the potential prospects of electrospun starch nanofibrous films in the food packaging field.

Interfacial Dipole poly(2-ethyl-2-oxazoline) Modification Triggers Simultaneous Band Alignment and Passivation for Air-Stable Perovskite Solar Cells.

To promote the performance of perovskite solar cells (PSCs), its theoretical power conversion efficiency (PCE) and high stability, elaborative defect passivation, and interfacial engineering at the molecular level are required to regulate the optoelectric properties and charge transporting process at the perovskite/hole transport layer (HTL) interfaces. Herein, we introduce for the first time a multifunctional dipole polymer poly(2-ethyl-2-oxazoline) (PEOz) between the perovskite and Spiro-OMeTAD HTL in planar n-i-p PSCs, which advances the PSCs toward both high efficiency and excellent stability by stimulating three beneficial effects. First, the ether-oxygen unshared electron pairs in PEOz chemically react with unsaturated Pb2+ on the perovskite surfaces by forming a strong Pb-O bond, which effectively reduces the uncoordinated defects on the perovskite surfaces and enhances the absorption ability of the resulting PSCs. Second, the dipole induced by PEOz at the perovskite/HTL interface can decrease the HOMO and LUMO level of Spiro-OMeTAD and optimize the band alignment between these layers, thereby suppressing the interfacial recombination and accelerating the hole transport/extraction ability in the cell. Third, the hygroscopic PEOz thin film can protect perovskite film from water erosion by absorbing the water molecules before perovskite does. Finally, the PEOz-modified PSC exhibits an optimized PCE of 21.86%, with a high short-circuit current density (Jsc) of 24.88 mA/cm2, a fill factor (FF) of 0.79, and an open-circuit voltage (Voc) of 1.11 V. The unencapsulated devices also deliver excellent operation stability over 300 h in an ambient atmosphere with a humidity of 30~40% and more than 10 h under thermal stress.

Structural and mechanistic insights into starch microgel/anthocyanin complex assembly and controlled release performance.

We report a self-assembly method for the fabrication of multilayer-starch-based microgels used for anthocyanin encapsulation. Alcohol-heating treatment and ionization reactions were employed to reduce the crystallinity of starch and introduce ionic groups on the molecule to further cross-link it with sodium trimetaphosphate and produce a starch microgel. The molecular interactions between the starch and the anthocyanins facilitated the anthocyanin encapsulation and the starch-microgel/anthocyanin complexes with one, two, and three self-assembled layers were obtained. The Lay-1 microgel exhibited an encapsulation efficiency of 50.1% when the anthocyanin concentration, cross-linking starch concentration, contact time, and temperature were 0.25 mg/mL, 1.5 mg/mL, 3 h, and 40 °C, respectively. An increase in the number of layers resulted in a more compact microgel structure with the zeta potential presenting variations upon structural changes. Furthermore, the encapsulated anthocyanins presented a slow release from Lay-1, while the multilayered microgels (Lay-2 and Lay-3) displayed outstanding encapsulation stability. This study gives an insight on the encapsulation and release of anthocyanins by starch microgels, and provides a novel strategy for the design of starch-based encapsulation materials presenting great stability.

An anatomical study of the origins courses and distributions of the transverse branches of lumbar arteries at the L1-L4 levels.

Pseudoaneurysms of the lumbar arteries following transforaminal lumbar interbody fusion (TLIF) are rare postoperative complications that usually occur around the transverse process. However, there are few detailed descriptions of the transverse branch and other branches of the dorsal branches at the L1-L4 disks. STUDY DESIGN: Ten adult embalmed cadavers were anatomically studied. OBJECTIVES: The purposes of the study were to describe the vascular distribution of the dorsal branches, especially the transverse branches, at the L1-L4 levels and provide information useful for TLIF. METHODS: Ten embalmed cadavers studied after their arterial systems were injected with red latex. The quantity, origin, pathway, distribution range and diameter of the branches were recorded and photographed. RESULTS: The transverse branch appeared in all 80 intervertebral foramina. The transverse branch was divided into 2 types: In type 1, the arteries divided into superior branches and inferior branches; the arteries in type 2 divided into 3 branches (superior, intermedius and inferior branches). CONCLUSIONS: The transverse branches of the dorsal arteries are common structures from L1 to L4, and 2 types of transverse branches were found. A thorough understanding of the dorsal branches, especially the transverse branches of the lumbar artery, may be very important for reducing both intraoperative bleeding during the surgery and the occurrence of pseudoaneurysms after transforaminal lumbar interbody fusion.

Anatomical study of the innervation of different parts of the posterior ligamentous region of the sacroiliac joint.

BACKGROUND AND OBJECTIVES: The periarticular sacroiliac joint (SIJ) technique has become an important area of focus, and the quartering of the SIJ posterior ligamentous region has been proposed as a way to refine this technique. However, detailed nerve distribution combined with the division of the SIJ posterior ligamentous region is lacking. We aimed to explore the innervation of the SIJ posteriorly based on the quartering of the SIJ posterior ligamentous region. METHODS: Sixteen SIJs from eight embalmed cadavers were studied. Each SIJ posterior ligamentous region was equally divided into areas 0-3 from top to bottom. The origin, distribution, quantity, transverse diameter, spatial orientation, relation with bony structures, and the number of identifiable terminal nerve branches in each area were examined. RESULTS: Areas 0-1 were innervated by the lateral branches of the dorsal rami of L4-L5 directly in all specimens. Areas 2-3 were innervated by that of both lumbar and sacral nerves via the posterior sacral network (PSN), with L5 contributing to the PSN in all specimens and L4 in 68.75%. The number of identifiable terminal nerve branches were significantly higher in areas 2-3 than in areas 0-1. CONCLUSIONS: The inferior part of the SIJ posterior ligamentous region seems to be the main source of SIJ-related pain and is innervated by lumbar and sacral nerves via the PSN. However, the superior part directly innervated by lumbar nerves should not be neglected, and further clinical verification is needed.

The anatomical mechanism of C5 palsy after expansive open-door laminoplasty.

BACKGROUND: Postoperative C5 palsy is not an uncommon complication in patients who undergo expansive open-door laminoplasty. However, the etiology is unclear and likely multifactorial. Nerve root lesions and spinal cord lesions have been previously proposed theories. PURPOSE: To investigate the anatomical mechanism of postoperative C5 palsy after cervical expansive open-door laminoplasty. STUDY DESIGN: A dissection-based study of eight embalmed human cadavers. METHODS: The anatomy was studied in eight whole cervical cadavers (three females, five males), prepared with formaldehyde, whose ages at the time of death ranged from 54 to 78 years. Dissection was performed on the intervertebral foramen and spinal canal. In the C3-C7 of the cervical vertebra, the extraforaminal ligaments and the meningovertebral ligaments were observed. The length, width, and thickness of the ligaments were measured with a Vernier caliper. After an expansive open-door laminoplasty was performed, the shape of the dural sac was changed, and displacement of the nerve root was observed. In addition, the lengths of the anterior rootlets were measured. This study has been supported by grants from Science and Technology Planning Project of Guangdong Province (CN) (Grant No. 2017B020210010) without potential conflict of interest-associated biases in the text of the paper. RESULTS: One hundred seventy-seven extraforaminal ligaments were found to connect the spinal nerve to the surrounding structures. After an expansive open-door laminoplasty was performed, posterior distension of the dural sac and movement of the spinal cord and nerve root were found. The spinal cord was closely attached to the ligamentum flavum by meningovertebral ligaments. In addition, the length of the C5 intradural rootlets (5.81-10.59 mm) was the shortest among the vulnerable segments. CONCLUSION: Traction on and posterior movement of the extradural roots may be the main pathologic mechanism of postoperative C5 palsy when expansive open-door laminoplasty is performed. The meningovertebral ligaments and extraforaminal ligaments might play an important role in the occurrence of postoperative C5 palsy. CLINICAL SIGNIFICANCE: This study provides clinicians with a more detailed understanding of the anatomic structure and potential mechanism of C5 palsy. Consideration of the meningovertebral ligaments and the intervertebral foramen may provide new directions for reducing the incidence of this complication.

Prevalence and characteristics of hepatitis C virus infection in Shenyang City, Northeast China, and prediction of HCV RNA positivity according to serum anti-HCV level: retrospective review of hospital data.

OBJECTIVE: The prevalence of hepatitis C virus (HCV) infection is typically evaluated based on the current rate of positivity of anti-HCV antibody; however, HCV RNA positivity is considered the main criterion for antiviral treatment of HCV infection in the clinical setting. In this study, we evaluated the prevalence of HCV infection based on anti-HCV and HCV RNA detection in the population of Liaoning Province, and investigated the correlation between serum HCV RNA positivity and anti-HCV levels. METHODS: A total of 192,202 patients who underwent serum anti-HCV examination at Shengjing Hospital in 2018 were enrolled in the study. Anti-HCV production was tested using a chemiluminescence assay, and serum HCV RNA detection was performed with Roche COBAS TaqMan (CTM) Analyzer. RESULTS: The prevalence of anti-HCV was 1.21 and 0.93% among male and female patients in Liaoning Province, respectively. The positive rates of anti-HCV and serum anti-HCV levels were both age-related, in which patients over 40 years of age had a significantly higher anti-HCV positive rate than those younger than 40 years. Among the anti-HCV-positive patients, the average HCV RNA positive rate was 51.66 and 35.93% in males and females, respectively. Spearman rank analysis showed a significantly positive correlation between serum HCV RNA positivity and the level of anti-HCV. The best cut-off value using serum anti-HCV levels to predict the positivity of HCV RNA was determined to be 9.19 signal-to-cut-off ratio (s/co) in males and 10.18 s/co in females. CONCLUSION: The prevalence of anti-HCV in the general population of Liaoning Province was around 1.04%, which was higher than that previously reported from a national survey of HCV infection in China. Approximately 42.9% of the anti-HCV-positive patients also tested positive for HCV RNA. However, the positive correlation between the serum anti-HCV and HCV RNA levels suggests that the positivity of serum HCV RNA can be predicted according to the anti-HCV level in anti-HCV-positive patients, which can improve screening and facilitate timely intervention to prevent the spread of infection.

Fluorodynamers Displaying Tunable Fluorescence on Constitutional Exchanges in Solution and at Solid Film-Solution Interface.

Dynamic covalent polymers-dynamers-are adaptive materials that offer timely variant adaptive macroscopic organization across extended scales. In the current study, imine exchange reactions and fluorescence transfer can occur at the interfaces between various solutions and solid state dynameric films. The fluorescence quenching upon imine formations for designed fluorogen was successfully demonstrated, and this tunable fluorescence was further used to study the re-composition of a solid film. Moreover, the dynamic covalent films also exhibited responsiveness to competing amines and acid/base conditions, both in solutions and solid film-solution interface. This work can provide more insights into interface dynamic chemistry and holds great potential for further applications in optical and biomedical materials.

The Prevalence of HBV Infection: A Retrospective Study of 13 Years in a Public Hospital of Northeast China.

The prevalence of hepatitis B virus (HBV) infection was an imbalance in different provinces of China. This study aimed to investigate the prevalence of HBV infection and evaluate the prophylactic measures in a public hospital of northeast China over the preceding 13 years. A total of 13,948 patients in 2004 and 15,256 patients in 2017 of Shengjing Hospital of China Medical University were tested of serum HBsAg, HBeAg, HBsAb, HBeAb, and HBcAb levels with Abbott MEIA Kits. In people born before 1992, HBsAg-positive rate was 5.45% and 6.47%; isolated HBsAb positive rate was 14.62% and 21.24%; HBV marker negative rate was 54.27% and 42.77% in 2004 and 2017 survey, respectively. The males had a significant higher HBsAg-positive rate than the females. In people born during 1992-2004, HBsAg positive rate was 0.58% and 0.57%, isolated HBsAb positive rate was 41.47% and 46.57%; and HBV marker negative rate was 51.97% and 46.86% in 2004 and 2017 survey, respectively. Males and females had no difference of HBsAg-positive rate. In children born after 2005, HBsAg positive rate was 0.11%, isolated HBsAb positive rate was 76.68%, and HBV marker negative rate was 18.51% in 2017 survey. No difference of HBsAg-positive rate was found between the genders. A dramatic decrease of HBsAg positive rate and a progressive increase of HBsAb-positive rate were found among people born after 1992 and progressed further in those born after 2005. Immunization of infants and timely birth dose was the key method for prevention of HBV infection. Expanded HB vaccination would be needed for people born before 2005, especially those born between 1992 and 2004.

A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection.

Aberrant apoptosis can lead to acute or chronic degenerative diseases. Mitochondrial outer membrane permeabilization (MOMP) triggered by the oligomerization of the Bcl-2 family proteins Bax/Bak is an irreversible step leading to execution of apoptosis. Here, we describe the discovery of small-molecule inhibitors of Bax/Bak oligomerization that prevent MOMP. We demonstrate that these molecules disrupt multiple, but not all, interactions between Bax dimer interfaces thereby interfering with the formation of higher-order oligomers in the MOM, but not recruitment of Bax to the MOM. Small-molecule inhibition of Bax/Bak oligomerization allowed cells to evade apoptotic stimuli and rescued neurons from death after excitotoxicity, demonstrating that oligomerization of Bax is essential for MOMP. Our discovery of small-molecule Bax/Bak inhibitors provides novel tools for the investigation of the mechanisms leading to MOMP and will ultimately facilitate development of compounds inhibiting Bax/Bak in acute and chronic degenerative diseases.

A dual reporter system for detecting RNA interactions in bacterial cells.

Detecting RNA-partner interactions in cells is often difficult due to a lack of suitable tools. Here we describe a dual reporter system capable of detecting intracellular interactions in which one of the partners is an RNA. The system utilizes two fluorescent proteins with similar maturation rates but distinct spectral properties, specifically cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP). By placing the CFP gene upstream and the YFP gene downstream of an RNA gene of interest, the production of YFP becomes sensitive to RNA-partner interaction, whereas the synthesis of CFP is not disturbed. Therefore, the RNA-partner interaction can be simply measured by the change in the ratio of fluorescence of YFP over CFP. The utility of our approach is demonstrated through verification of three known RNA-partner interactions in the model bacterium Escherichia coli. Our two-reporter strategy should be broadly useful to the study of RNA-targeted interactions in bacteria.

tBid undergoes multiple conformational changes at the membrane required for Bax activation.

Bid is a Bcl-2 family protein that promotes apoptosis by activating Bax and eliciting mitochondrial outer membrane permeabilization (MOMP). Full-length Bid is cleaved in response to apoptotic stimuli into two fragments, p7 and tBid (p15), that are held together by strong hydrophobic interactions until the complex binds to membranes. The detailed mechanism(s) of fragment separation including tBid binding to membranes and release of the p7 fragment to the cytoplasm remain unclear. Using liposomes or isolated mitochondria with fluorescently labeled proteins at physiological concentrations as in vitro models, we report that the two components of the complex quickly separate upon interaction with a membrane. Once tBid binds to the membrane, it undergoes slow structural rearrangements that result in an equilibrium between two major tBid conformations on the membrane. The conformational change of tBid is a prerequisite for interaction with Bax and is, therefore, a novel step that can be modulated to promote or inhibit MOMP. Using automated high-throughput image analysis in cells, we show that down-regulation of Mtch2 causes a significant delay between tBid and Bax relocalization in cells. We propose that by promoting insertion of tBid via a conformational change at the mitochondrial outer membrane, Mtch2 accelerates tBid-mediated Bax activation and MOMP. Thus the interaction of Mtch2 and tBid is a potential target for therapeutic control of Bid initiated cell death.