The effect of top-down attention on empathy fatigue.

Prolonged exposure to others' suffering can lead to empathy fatigue, especially when individuals struggle to effectively regulate their empathic capacity. Shifting active attention away from emotional components toward cognitive components of others' suffering is an effective strategy for mitigating empathy fatigue. This research investigated how top-down attentional manipulation modulates empathy fatigue in both auditory (Study 1) and visual (Study 2) modalities. Participants completed two tasks in both studies: (i) the attention to cognitive empathy task (A-C task) and (ii) the attention to emotional empathy task (A-E task). Each task included three blocks (Time Block 1, Time Block 2, and Time Block 3) designed to induce empathy fatigue. Study 1 revealed that the A-C task reduced empathy fatigue and N1 amplitudes than the A-E task in Time Block 3, indicating that attention to cognitive empathy might decrease auditory empathy fatigue. Study 2 indicates that the A-C task caused a longer N2 latency than the A-E task, signifying a decelerated emotional empathic response when attention was on cognitive empathy in the visual modality. Overall, prioritizing cognitive empathy seems to conserve mental resources and reduce empathy fatigue. This research documented the relationship between top-down attention and empathy fatigue and the possible neural mechanism.

Lanthanide-Assisted Nanozyme Performs Optical and Magnetic Resonance Dual-Modality Logical Signal for In Vitro Diagnosis.

The iron nanozyme-based colorimetric method, which is widely applied for biosubstrate detection in in vitro diagnosis (IVD), faces some limitations. The optimal catalytic conditions of iron nanozymes necessitate a strong acidic environment, high temperature, and other restrictive factors; additionally, the colorimetric results are highly influenced by optical interferences. To address these challenges, iron nanozymes doped with various transition elements were efficiently prepared in this study, and notably, the manganese-modified one displayed a high catalytic activity owing to its electron transfer property. Furthermore, the introduction of lanthanide ions into the catalytic reactions, specifically the neodymium ion, significantly boosted the generation efficiency of hydroxyl radicals; importantly, this enhancement extended to a wide range of pH levels and temperatures, amplifying the detection signal. Moreover, the nanozyme's superparamagnetic characteristic was also employed to perform a logical optical and magnetic resonance dual-modality detection for substrates, effectively eliminating background optical interference and ensuring a reliable verification of the signal's authenticity. Based on this magnetic signal, the integration of natural glucose oxidase with the nanozyme resulted in a notable 61.5% increase in detection sensitivity, surpassing the capabilities of the traditional colorimetric approach. Consequently, the incorporation of lanthanide ions into the magnetic nanozyme enables the effective identification of physiological biomarkers through the dual-modality signal. This not only guarantees enhanced sensitivity but also demonstrates significant potential for future applications.

Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome.

Suppressing the background of LC-ESI-MS analysis of permethylated glycans using the active background ion reduction device.

Mass spectrometry (MS) has revolutionized analytical chemistry, enabling precise identification and quantification of chemical species, which is pivotal for biomarker discovery and understanding complex biological systems. Despite its versatility, the presence of background ions in MS analysis hinders the sensitive detection of low-abundance analytes. Therefore, studies aimed at lowering background ion levels have become increasingly important. Here, we utilized the commercially available Active Background Ion Reduction Device (ABIRD) to suppress background ions and assess its effect on the liquid chromatography-electrospray ionization (LC-ESI)-MS analyses of N-glycans on the Q Exactive HF mass spectrometer. We also investigated the effect of different solvent vapors in the ESI source on N-glycan analysis by MS. ABIRD generally had no effect on high-mannose and neutral structures but reduced the intensity of some structures that contained sialic acid, fucose, or both when methanol vapor filled the ESI source. Based on our findings on the highest number of identified N-glycans from human serum, methanol vapor in the ion source compartment may enhance N-glycan LC-ESI-MS analyses by improving the desolvation of droplets formed during the ESI process due to its high volatility. This protocol may be further validated and extended to advanced bottom-up proteomic/glycoproteomic studies for the analysis of peptide/glycopeptide ions by MS.

[Clinical remission and transmural healing of ustekinumab in patients with Crohn's disease].

OBJECTIVE: To treat the Crohn's disease (CD) patients with ustekinumab (UST), to eva-luate their clinical and endoscopic remission, and to evaluate their transmural response (TR) and transmural healing (TH) condition using intestinal ultrasonography (IUS). METHODS: Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to August 2022, who were treated with UST for remission induction and maintenance therapy. All the patients were evaluated on both week 8 and week 16/20 after treatment, including clinical, biochemical indicators, colonoscopy and IUS examination. RESULTS: A total of 13 patients were enrolled in this study, including 11 males and 2 females. The minimum age was 23 years, the maximum age was 73 years and the mean age was 36.92 years. All the patients were in the active stage of disease before treatment, and the average Best Crohn's disease activity index (Best CDAI) score was 270.12±105.55. In week 8, the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66 (t=4.977, P < 0.001). Eight patients achieved clinical remission while 5 patients remained in the active stage. Nine patients underwent colonoscopy evaluation. The average simple endoscopic score for Crohn's disease (SES-CD) score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483, P=0.048) in week 16/20. Four patients achieved endoscopic remission while 5 patients did not. In week 8, 5 patients achieved TR, 2 patients achieved TH, the other 6 patients did not get TR or TH. In week 16/20, 6 patients achieved TR, 3 patients achieved TH while the other 4 patients did not get TR or TH. There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions (Fisher test, P > 0.999). The rate of UST transmural response in the patients who had had previous biological agent therapy was lower than those with no previous biological agent therapy, but there was no significant statistical difference (Fisher test, P=0.491). CONCLUSION: After treatment of UST, the clinical and endoscopic conditions of the CD patients had been improved, and some patients could achieve clinical remission and endoscopic remission. UST had good TR and TH effects on CD. TR might appear in week 8, and the TR effect increased in week 16/20. There was no significant statistical difference in the TR effect between small intestine and colon lesions. TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents, but the result had no significant statistical difference.

Adaptive randomization in a two-stage sequential multiple assignment randomized trial.

Sequential multiple assignment randomized trials (SMARTs) are systematic and efficient media for comparing dynamic treatment regimes (DTRs), where each patient is involved in multiple stages of treatment with the randomization at each stage depending on the patient's previous treatment history and interim outcomes. Generally, patients enrolled in SMARTs are randomized equally to ethically acceptable treatment options regardless of how effective those treatments were during the previous stages, which results in some undesirable consequences in practice, such as low recruitment, less retention, and lower treatment adherence. In this article, we propose a response-adaptive SMART (RA-SMART) design where the allocation probabilities are imbalanced in favor of more promising treatments based on the accumulated information on treatment efficacy from previous patients and stages. The operating characteristics of the RA-SMART design relative to SMART design, including the consistency and efficiency of estimated response rate under each DTR, the power of identifying the optimal DTR, and the number of patients treated with the optimal and the worst DTRs, are assessed through extensive simulation studies. Some practical suggestions are discussed in the conclusion.

Incidence and prediction of HBsAg seroclearance in a prospective multi-ethnic HBeAg-negative chronic hepatitis B cohort.

BACKGROUND AND AIMS: Achieving HBsAg loss is an important landmark in the natural history of chronic hepatitis B (CHB). A more personalized approach to prediction of HBsAg loss is relevant in counseling patients. This study sought to develop and validate a prediction model for HBsAg loss based on quantitative HBsAg levels (qHBsAg) and other baseline characteristics. METHODS: The Hepatitis B Research Network (HBRN) is a prospective cohort including 1240 untreated HBeAg-negative patients (1150 adults, 90 children) with median follow-up of 5.5 years. Incidence rates of HBsAg loss and hepatitis B surface antibody (anti-HBs) acquisition were determined, and a predictor score of HBsAg loss using readily available variables was developed and externally validated. RESULTS: Crude incidence rates of HBsAg loss and anti-HBs acquisition were 1.6 and 1.1 per 100 person-years (PY); 67 achieved sustained HBsAg loss for an incidence rate of 1.2 per 100 PY. Increased HBsAg loss was significantly associated with older age, non-Asian race, HBV phenotype (inactive CHB vs. others), HBV genotype A, lower HBV-DNA levels, and lower and greater change in qHBsAg. The HBRN-SQuARe (sex,∆quantHBsAg, age, race) score predicted HBsAg loss over time with area under the receiver operating characteristic curve (AUROC) (95% CIs) at 1 and 3 years of 0.99 (95% CI: 0.987-1.00) and 0.95 (95% CI 0.91-1.00), respectively. In validation in another cohort of 1253 HBeAg-negative patients with median follow-up of 3.1 years, HBRN SQuARe predicted HBsAg loss at 1 and 3 years with AUROC values of 0.99 (0.98-1.00) and 0.88 (0.77-0.99), respectively. CONCLUSION: HBsAg loss in predominantly untreated patients with HBeAg-negative CHB can be accurately predicted over a 3-year horizon using a simple validated score (HBRN SQuARe). This prognostication tool can be used to support patient care and counseling.

Interim monitoring in sequential multiple assignment randomized trials.

A sequential multiple assignment randomized trial (SMART) facilitates the comparison of multiple adaptive treatment strategies (ATSs) simultaneously. Previous studies have established a framework to test the homogeneity of multiple ATSs by a global Wald test through inverse probability weighting. SMARTs are generally lengthier than classical clinical trials due to the sequential nature of treatment randomization in multiple stages. Thus, it would be beneficial to add interim analyses allowing for an early stop if overwhelming efficacy is observed. We introduce group sequential methods to SMARTs to facilitate interim monitoring based on the multivariate chi-square distribution. Simulation studies demonstrate that the proposed interim monitoring in SMART (IM-SMART) maintains the desired type I error and power with reduced expected sample size compared to the classical SMART. Finally, we illustrate our method by reanalyzing a SMART assessing the effects of cognitive behavioral and physical therapies in patients with knee osteoarthritis and comorbid subsyndromal depressive symptoms.

A Reciprocal Best-hit Approach to Characterize Isomeric N-Glycans Using Tandem Mass Spectrometry.

Glycosylation is a post-translational modification involved in many important biological functions. The aberrant alteration of glycan structure is implicit with malfunction of cells and possess potential significance in medical diagnosis of complex diseases such as cancer. Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been commonly applied to the analysis of complex glycomic samples. However, the characterization of isomeric glycans from their MS/MS spectra in complex biological samples remains challenging. In this paper, we present a novel reciprocal best-hit glycan-spectrum matching (RB-GSM) approach toward characterizing N-glycans. In this method, the MS/MS spectra in the input data set are evaluated against all glycans with the matched precursor mass using customized scoring functions, where a glycan-spectrum matching (GSM) is considered to be true if it is a reciprocal best-hit, that is, it receives the highest score among not only the GSMs between the respective spectrum and all matched glycans, but also the GSMs between the respective glycan and all matched MS/MS spectra in the input data set. We evaluated this RB-GSM approach on N-glycan identification using MS/MS spectra acquired from glycan standards as well as those released from the model glycoprotein fetuin, immunoglobulin G, and human serum samples, which showed the RB-GSM is capable of distinguishing isomeric glycans.

Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate hepatitis B e antigen (HBeAg) production respectively. PC mutation is rarely associated with HBV genotype A. We sought to examine the association of these variants with HBV genotypes, age, and HBeAg status in a racially diverse population in North America. Prospective study included 1,036 (808 adults, 228 children) participants in the Hepatitis B Research Network. PC and BCP variants were determined by Sanger sequencing, and dominant HBV species (>50%) were reported. APPROACH AND RESULTS: Median age was 36.3 years (range, 2-80), 44.6% HBeAg(+), 74.2% Asians, 13.3% black, and 9.7% white. The dominant PC variant was present in 29.4% participants, including 20 with subgenotype A1 or A2. Seventeen of 20 participants with genotype A and PC had a compensatory C1858T mutation. In the HBeAg(+) cohort, the prevalence of PC and/or BCP variants increased from 14.4% in the first two decades to 51% after 40 years of age. Among those aged 2-18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001). CONCLUSIONS: PC variants can be present in HBV genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Selection of PC and BCP variants occurred at a young age, with increasing prevalence across age groups. HBeAg(+) participants with dominant PC and BCP variants progressed to the HBeAg(-) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.

Advances in mass spectrometry-based glycomics-An update covering the period 2017-2021.

The wide variety of chemical properties and biological functions found in proteins is attained via post-translational modifications like glycosylation. Covalently bonded to proteins, glycans play a critical role in cell activity. Complex structures with microheterogeneity, the glycan structures that are associated with proteins are difficult to analyze comprehensively. Recent advances in sample preparation methods, separation techniques, and MS have facilitated the quantitation and structural elucidation of glycans. This review focuses on highlighting advances in MS-based techniques for glycomic analysis that occurred over the last 5 years (2017-2021) as an update to the previous review on the subject. The topics of discussion will include progress in glycomic workflow such as glycan release, purification, derivatization, and separation as well as the topics of ionization, tandem MS, and separation techniques that can be coupled with MS. Additionally, bioinformatics tools used for the analysis of glycans will be described.

Isomeric separation of permethylated glycans by extra-long reversed-phase liquid chromatography (RPLC)-MS/MS.

Glycosylation is known as a critical biological process that can largely affect the properties and the functions of proteins. Glycan isomers have been shown to be involved in a variety of disease progressions. However, the separation and identification of glycan isomers has been a challenge for years due to the microheterogeneity of glycan isomeric structures. Therefore, effective and stable techniques have been investigated over the last few decades to improve isomeric separations of glycans. RPLC has been widely used in biomolecule analysis because of its extraordinary reproducibility and reliability in retention time and separation resolution. However, so far, no studies have achieved high resolution of glycan isomers using this technique. In this study, we focused on further boosting the isomeric separation of permethylated glycans using a 500 mm reversed-phase LC column. To achieve better resolutions on permethylated glycans, different LC conditions were optimized using glycan standards, including core- and branch-fucosylated N-glycan isomers and sialic acid linked isomers, which were both successfully separated. Then, the optimal separation strategy was applied to achieve separations of N- and O-glycan isomers derived from model glycoproteins, including bovine fetuin, ribonuclease B and κ-casein. Baseline separations were observed on multiple sialylated linkage isomers. However, the separation performance of high-mannose isomers needs further improvement. The reproducibility and stability of this long C18 column was also tested by doing run-to-run, day-to-day and month-to-month comparisons of retention times on multiple glycans and the %RSD was found less than 0.92%. Finally, we applied this approach to separate glycan isomers derived from complex biological samples, including blood serum and cell lines, where baseline separations were attained on several isomeric structures. Compared to the separation efficiency of PGC and MGC columns, the RPLC C18 column provides lower resolution but more robust reproducibility, which makes it a good complementary alternative for isomeric separations of glycans.

Near-surface atmospheric turbulence profile measuring technology based on an airship-mounted laser communication system.

Atmospheric turbulence is an important factor affecting the transmission performance of free-space optical communications (FSOC), especially in the near-surface where the atmospheric turbulence characteristics are complex and variable. In this paper, we study the real-time measurement technique of a near-surface atmospheric turbulence profile of an airship-borne laser communication system based on the principle of light intensity scintillation. Aiming at the influence of an avalanche photon diode detector system noise and environmental factors such as background light and platform vibration on the measurement results, a noise-canceling scintillation index calculation method, combined with a wavelet threshold denoising method, is proposed to improve the accuracy of atmospheric turbulence profile measurements. We build a communication distance of 12 km airship-borne laser communication experiment and carry out a real-time measurement of turbulence profile under 1 km near the ground without affecting the laser communication rate of 2.5 Gbps data transmission. The experimental results show that the atmospheric turbulence profile measured in real time follows the same trend as the theoretical simulation curve of the Hufnagel-Valley model, and the jitter of the measured values after denoising is significantly smaller than that of the measured values without denoising. The research results provide technical guidance and data support to promote the development of space laser communication and adaptive optics.

The RNA-binding protein HuR regulates intestinal epithelial restitution by modulating Caveolin-1 gene expression.

The integrity of the intestinal mucosal barrier protects hosts against pathological conditions. Early mucosal restitution after wounding refers to epithelial cell migration into a defect. The RNA-binding protein HuR plays an important role in the posttranscriptional regulation of gene expression and is involved in many aspects of cellular physiology. In the present study, we investigated the role of HuR in the regulation of cell migration through the posttranscriptional regulation of Caveolin-1 (Cav-1). Online software was used to identify Cav-1 mRNA as a potential target of HuR. The interaction of HuR with Cav-1 mRNA was investigated via ribonucleoprotein immunoprecipitation (RNP IP) assays and biotin pulldown analysis. HuR was found to bind specifically to the Cav-1 3'-UTR rather than the coding region or 5'-UTR. Transfection of cells with siHuR decreased both HuR protein levels and Cav-1 protein levels; conversely, ectopic overexpression of HuR via infection of cells with an adenoviral vector containing HuR cDNA (AdHuR) increased Cav-1 protein levels without disturbing Cav-1 mRNA levels. Thus, HuR enhanced Cav-1 expression in vitro by stimulating Cav-1 translation. Intestinal epithelium-specific HuR knockout in mice decreased Cav-1 protein levels without changing Cav-1 mRNA levels, consistent with the in vitro results. Decreasing the levels of HuR via siHuR transfection inhibited early epithelial repair, but this effect was reversed by ectopic overexpression of GFP-tagged Cav-1. These results indicate that posttranscriptional regulation of Cav-1 gene expression by HuR plays a critical role in the regulation of rapid epithelial repair after wounding.

Sphingolipid synthesis inhibitor fumonisin B1 causes verticillium wilt in cotton.

Verticillium wilt caused by Verticillium dahliae is a major disease of cotton. Acidic protein-lipopolysaccharide complexes are thought to be the toxins responsible for its symptoms. Here, we determined that the sphingolipid biosynthesis inhibitor fumonisin B1 (FB1) acts as a toxin and phenocopies the symptoms induced by V. dahliae. Knocking out genes required for FB1 biosynthesis reduced V. dahliae pathogenicity. Moreover, we showed that overexpression of a FB1 and V. dahliae both downregulated gene, GhIQD10, enhanced verticillium wilt resistance by promoting the expression of brassinosteroid and anti-pathogen genes. Our results provide a new strategy for preventing verticillium wilt in cotton.

Hepatitis B e antigen loss in adults and children with chronic hepatitis B living in North America: A prospective cohort study.

Hepatitis B e antigen (HBeAg) is a soluble viral protein in plasma of patients with hepatitis B virus infection. HBeAg loss is an important first stage of viral antigen clearance. We determined the rate and predictors of HBeAg loss in a North American cohort with chronic hepatitis B viral infection (CHB). Among children and adults with CHB and without HIV, HCV or HDV co-infection enrolled in the Hepatitis B Research Network prospective cohort studies, 819 were HBeAg positive at their first assessment (treatment naïve or >24 weeks since treatment). Of these, 577 (200 children, 377 adults) were followed every 24-48 weeks. HBeAg loss was defined as first HBeAg-negative value; sustained HBeAg loss was defined as ≥2 consecutive HBeAg-negative values ≥24 weeks apart. During a median follow-up of 1.8 years, 164 participants experienced HBeAg loss, a rate of 11.4 (95% CI, 9.8-13.3) per 100 person-years. After adjustment for confounders, HBeAg loss rate was significantly higher in males than females, in older than younger individuals, in Whites or Blacks than Asians, in those with genotype A2 or B versus C, and in those with basal core promoter/pre-core mutations versus wild type. Additionally, during follow-up, an ALT flare and a lower quantitative HBsAg, quantitative HBeAg or HBV DNA level predicted higher rates of HBeAg loss. The majority (88%) with HBeAg loss had sustained HBeAg loss. In conclusion, a number of specific demographic, clinical and viral characteristics impacted rate of HBeAg loss and may prove useful in design and interpretation of future therapeutic studies.

Expression of a Beauveria bassiana chitosanase (BbCSN-1) in Pichia pastoris and enzymatic analysis of the recombinant protein.

Chitosanase (EC 3.2.1.132) is an important chitosan-degrading enzyme involved in industrial applications. In this study, a chitosanase gene (BbCSN-1) from Beauveria bassiana, an insect fungal pathogen, was cloned and expressed in Pichia pastoris. The amount of BbCSN-1 in the fermentation broth of P. pastoris gradually increased after induction with methanol from one to 6 d, reaching 398 µg/ml on the 6th day. The molecular characteristics of BbCSN-1 were measured with colloidal chitosan as a substrate. The purified BbCSN-1 exhibited optimum activity at pH 5 and 30 °C and was stable at pH 2-8 and below 40 °C. The Km value of BbCSN-1 was approximately 0.8 mg/ml at 30 °C (pH 6.0). The activity of BbCSN-1 was significantly enhanced by Mn2+ but inhibited by Co2+ and Cu2+. These results indicated that BbCSN-1 from B. bassiana could be easily expressed in P. pastoris, which provided a basis for further study on its application.

Identification of herbal categories active in pain disorder subtypes by machine learning help reveal novel molecular mechanisms of algesia.

Chronic pain is highly prevalent and poorly controlled, of which the accurate underlying mechanisms need be further elucidated. Herbal drugs have been widely used for controlling various pain disorders. The systematic integration of pain herbal data resources might be promising to help investigate the molecular mechanisms of pain phenotypes. Here, we integrated large-scale bibliographic literatures and well-established data sources to obtain high-quality pain relevant herbal data (i.e. 426 pain related herbs with their targets). We used machine learning method to identify three distinct herb categories with their specific indications of symptoms, targets and enriched pathways, which were characterized by the efficacy of treatment to the chronic cough related neuropathic pain, the reproduction and autoimmune related pain, and the cancer pain, respectively. We further detected the novel pathophysiological mechanisms of the pain subtypes by network medicine approach to evaluate the interactions between herb targets and the pain disease modules. This work increased the understanding of the underlying molecular mechanisms of pain subtypes that herbal drugs are participating and with the ultimate aim of developing novel personalized drugs for pain disorders.

Alcohol, tobacco and coffee consumption and liver disease severity among individuals with Chronic Hepatitis B infection in North America.

INTRODUCTION AND OBJECTIVES: The prevalence of alcohol, tobacco, and coffee use and association with liver health among North Americans with Chronic Hepatitis B (CHB) infection has not been well described. MATERIALS AND METHODS: The Hepatitis B Research Network includes an observational study of untreated CHB adults enrolled at 21 sites in the United States and Canada. Alcohol use was categorized as none, moderate, and at-risk based on the definition from the National Institute on Alcohol Abuse and Alcoholism; tobacco use as never, current and former; coffee use as none, 1-2 cups/day, and ≥3 cups/day. Linear regression and linear mixed models were used to associate lifestyle behaviors with ALT and FIB-4 values. RESULTS: 1330 participants met eligibility: 53% males, 71% Asian and the median age was 42 years (IQR: 34-52). Median ALT was 33U/L (IQR: 22-50), 37% had HBV DNA <103IU/mL, 71% were HBeAg negative, and 65% had a FIB-4 <1.45. At baseline, 8% of participants were at-risk alcohol drinkers, 11% were current smokers and 92% drank <3 cups of coffee/day. Current tobacco and 'at-risk' alcohol use, were significantly associated with elevated ALT levels in univariable analyses, however, these associations were not statistically significant when controlling for sociodemographic and HBV characteristics. CONCLUSIONS: In this large diverse cohort of untreated CHB participants, at-risk alcohol use, current tobacco use and limited coffee consumption did not have an association with high ALT and FIB-4 values. In contrast, significant associations were found between the frequency of these lifestyle behaviors and sociodemographic factors.

A polyketide synthase, BbpksP, contributes to conidial cell wall structure and UV tolerance in Beauveria bassiana.

Conidial pigments of filamentous fungi play vital roles in fungal biotic/abiotic stress tolerance and are usually synthesized by polyketide synthases or other pigment synthesis proteins. Beauveria bassiana, an important insect pathogenic fungus used worldwide for pest biocontrol, produces white conidia on artificial media, while no conidial pigment has been observed or reported in it. However, real-time PCR and promoter-report analyses reveal a polyketide gene of B. bassiana (named BbpksP), homologous to melanin synthesis genes, is specifically expressed in aerial conidia. We show that deletion of BbpksP does not result in changes in conidial yield, germination rate or colony radial growth; however, the defect impairs conidial cell wall structure. A dense electron layer appears in the outer edge of the cell envelope in wild-type conidia, as observed by TEM, but this dense layer is absent in the ΔBbpksP mutant. The lack of BbpksP gene also reduces the UV-B tolerance of B. bassiana conidia. Bioassay reveals that deletion of BbpksP decreased virulence of B. bassiana against Galleria mellonella larvae via topical infection. These data indicate that the product(s) of BbpksP contributes to the integrity of the B. bassiana conidial cell wall and further affects the tolerance of UV-B stress and insecticidal activity.