The catabolic specialization of the marine bacterium Polaribacter sp. Q13 to red algal ß1,3/1,4-mixed-linkage xylan.

Catabolism of algal polysaccharides by marine bacteria is a significant process of marine carbon cycling. ß1,3/1,4-Mixed-linkage xylan (MLX) is a class of xylan in the ocean, widely present in the cell walls of red algae. However, the catabolic mechanism of MLX by marine bacteria remains elusive. Recently, we found that a marine Bacteroidetes strain, Polaribacter sp. Q13, is a specialist in degrading MLX, which secretes a novel MLX-specific xylanase. Here, the catabolic specialization of strain Q13 to MLX was studied by multiomics and biochemical analyses. Strain Q13 catabolizes MLX with a canonical starch utilization system (Sus), which is encoded by a single xylan utilization locus, XUL-Q13. In this system, the cell surface glycan-binding protein SGBP-B captures MLX specifically, contributing to the catabolic specificity. The xylanolytic enzyme system of strain Q13 is unique, and the enzymatic cascade dedicates the stepwise hydrolysis of the ß1,3- and ß1,4-linkages in MLX in the extracellular, periplasmic, and cytoplasmic spaces. Bioinformatics analysis and growth observation suggest that other marine Bacteroidetes strains harboring homologous MLX utilization loci also preferentially utilize MLX. These results reveal the catabolic specialization of MLX degradation by marine Bacteroidetes, leading to a better understanding of the degradation and recycling of MLX driven by marine bacteria.IMPORTANCERed algae contribute substantially to the primary production in marine ecosystems. The catabolism of red algal polysaccharides by marine bacteria is important for marine carbon cycling. Mixed-linkage ß1,3/1,4-xylan (MLX, distinct from hetero-ß1,4-xylans from terrestrial plants) is an abundant red algal polysaccharide, whose mechanism of catabolism by marine bacteria, however, remains largely unknown. This study reveals the catabolism of MLX by marine Bacteroidetes, promoting our understanding of the degradation and utilization of algal polysaccharides by marine bacteria. This study also sets a foundation for the biomass conversion of MLX.

N6-methyladenosine in hematological malignancies: a concise review.

PURPOSE OF REVIEW: Hematological malignancies are a kind of systemic cancers mostly related to abnormal differentiation of blood stem cells. Because of the poor prognosis, chemotherapy resistance and common recurrence, new mechanisms and treatment therapies are looking forward to be discovered. RECENT FINDINGS: Over the years, epigenetic abnormalities have been known to act a key part in occurrence and development of hematological tumors. In the internal modifications on long noncoding eukaryotic mRNA, there is a common type called N6-methyladenosine that can change the expression of target genes and participate in the translation, degradation and splicing of mRNA. M6A is related to a wealth of cancers, such as HNRNPA2B1's elevation in multiple myeloma, METTLE3's elevation in acute myeloid leukemia and lung cancer. Immune cells, playing a significant role in hematological cancers, can also be regulated by m6A. SUMMARY: In the review, we summarized the recent progress on hematological malignancies associating with m6A and immune cells, which may offer a new road for the treatment of them.

LOC101929709 promotes gastric cancer progression by aiding LIN28B to stabilize c-MYC mRNA.

BACKGROUND: LIN28B plays a critical role in the Warburg effect. However, its underlying mechanism remains elusive. Recently, it has been reported that LIN28B could collaborate with IGF2BP3, which can bind to m6A-modified c-MYC transcripts. Therefore, this study investigated if LIN28B recognises methylated c-MYC mRNA to promote the Warburg effect in gastric cancer. METHODS: Effects of LIN28B on gastric cancer were confirmed in vitro and in vivo. On the basis of bioinformatics analysis, the association between LIN28B and c-MYC mRNA was shown using RNA immunoprecipitation (RIP) and luciferase reporter assays. The role of m6A was identified by RNA pull-down assays. We further performed RIP-seq to search for long non-coding RNAs (lncRNAs) participating in the LIN28B binding process. Chromatin immunoprecipitation was used to show the impact of c-MYC on transcription of LIN28B and lncRNAs. RESULTS: LIN28B was identified to stabilize c-MYC mRNA by recognizing m6A. Furthermore, the interaction between c-MYC mRNA and LIN28B is speculated to be supported by LOC101929709, which binds to both LIN28B and IGF2BP3. Functional experiments revealed that LOC101929709 promotes the proliferation, migration and glycolysis of gastric cancer. Mechanistically, LOC101929709 enriched in the cytoplasm helps LIN28B stabilize c-MYC mRNA. Moreover, c-MYC promoted the transcription of both LOC101929709 and LIN28B. Additionally, LOC101929709 also activated the PI3K/AKT pathway. CONCLUSIONS: The c-MYC/LOC101929709/LIN28B axis promotes aerobic glycolysis and tumour progression. Thus, LOC101929709 can be a novel potential target for gastric cancer treatment.

Ocular Mycobacterium haemophilum infection originating in the cornea: a case report.

BACKGROUND: Mycobacterium haemophilum is a slow-growing non-chromogenic nontuberculous Mycobacterium species that can cause skin infection or arthritis in an immunocompromised population or in children. Primary infection of the healthy adult cornea is rare. The special requirements for culture make this pathogen difficult to diagnose. The study aims to report the clinical manifestation and treatment process of corneal infection and notify the awareness of M. Haemophilus keratitis among clinicians. This is the first case report of primary M. haemophilum infection in the cornea of healthy adults reported in the literature. CASE PRESENTATION: A 53-year-old healthy goldminer presented with left eye redness and a history of vision loss for four months. The patient was misdiagnosed with herpes simplex keratitis until M. haemophilum was detected using high-throughput sequencing. Penetrating keratoplasty was performed, and a large number of mycobacteria were detected by Ziehl-Neelsen staining of the infected tissue. Three months later, the patient developed conjunctival and eyelid skin infections that manifested as caseous necrosis of the conjunctiva and skin nodules. After excision and debridement of the conjunctival lesions and systemic antituberculosis drug treatment for 10 months, the patient was cured. CONCLUSION: M. haemophilum could cause primary corneal infection in healthy adults, which is an infrequent or rare infection. Owing to the need for special bacterial culture conditions, conventional culture methods do not provide positive results. High-throughput sequencing can rapidly identify the presence of bacteria, which aids in early diagnosis and timely treatment. Prompt surgical intervention is an effective treatment option for severe keratitis. Long-term systemic antimicrobial therapy is crucial.

Underlying Degradation of Phthalates via Microbials in Dust from Different Microenvironments.

Phthalate monoesters (me-PAEs) have been used as biomarkers for assessing human exposure to phthalate esters (PAEs) for a long time, and studies on the sources and distribution of me-PAEs in the environment are limited. In this study, dust samples from microenvironments were collected to measure the occurrence of PAEs and me-PAEs, as well as the bacterial diversity. The results indicated that me-PAEs coexisted with PAEs in different microenvironmental dust samples, with concentrations of nine PAEs and 16 me-PAEs ranging from 108 to 1450 µg/g (median range) and 6.00 to 21.6 µg/g, respectively. The concentrations of several low molecular weight me-PAEs (e.g., monomethyl phthalate and monoethyl phthalate) in dust were even significantly higher than those of their parents. The bacteria in the dust were mainly predominant with Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes (total abundance >90%). Bacteria from bus and air conditioning dust samples had the highest species richness and species diversity. Seven genes of suspected enzymes with the ability to degrade PAEs were selected, and the concentration of me-PAEs increased with increasing abundance of enzyme function. Our findings will provide useful information on the profiles of me-PAEs and their potential sources in indoor dusts, which will benefit the accurate estimation of human exposure.

Efficacy of two opportunistic methods for screening osteoporosis in lumbar spine surgery patients.

PURPOSE: Hounsfield unit (HU) measurements and vertebral bone quality (VBQ) scores are opportunistic screening methods for evaluating bone quality. Since studies comparing the efficacies of the two methods are rare, this retrospective study aimed to examine the efficacy of VBQ scores compared with that of HU measurements for diagnosing osteoporosis in lumbar spine surgery patients. METHODS: We selected patients who had undergone spinal surgery between January 2020 and May 2022 from our database. The VBQ scores based on magnetic resonance imaging (MRI) and HU measurements based on computed tomography (CT) were calculated. Correlation analysis of the dual-energy X-ray absorptiometry (DEXA) T score and study parameters was performed. The Delong test and decision curve analysis (DCA) were used to compare the efficacies of the two methods. RESULTS: We included 118 consecutive patients who underwent selective spinal surgery. The VBQ score and HU measurement were significantly correlated with the DEXA T score. Based on the Delong test, HU measurement predicted osteoporosis more effectively than the VBQ score did. The DCA revealed that the VBQ score performed better than the HU measurement did. CONCLUSIONS: The calculation of VBQ scores is a novel opportunistic screening method for diagnosing osteoporosis; however, CT-based HU measurements outperform MRI-based VBQ scores. HU measurements can be used as a screening method when pre-operative CT scans are available.

Risk factors of delirium in a paediatric intensive care unit: A prospective case series study.

BACKGROUND: Delirium is one of the most common complications in critically ill children. Once delirium occurs, it will cause physical and psychological distress in children and increase the length of their ICU stay and hospitalization costs. Understanding the risk factors for delirium in critically ill children can help develop targeted nursing interventions to reduce the incidence of delirium. AIMS: To investigate the incidence and the risk factors of delirium in the paediatric intensive care unit (PICU). STUDY DESIGN: We performed a prospective observational study in critically ill patients in the PICU between February and July 2020. Delirium was diagnosed by the Cornell Assessment of Paediatric Delirium (CAPD) and the Richmond Agitation Sedation Scale and analysed via univariate analysis and multivariate logistic regression to determine the independent risk factors of delirium in critically ill children. RESULTS: The study enrolled 315 patients ranging in age from 1-202 (65.3-54.3) months, with 56.2% (n = 177) being male. The incidence of delirium was 29.2% (n = 92) according to CAPD criteria. Among them, 33 cases (35.9%) were of hyperactive delirium, 16 cases (17.4%) were of hypoactive delirium, and 43 cases (46.7%) were of mixed delirium. By using stepwise logistic regression, the independent risk factors of delirium included mechanical ventilation (odds ratio [OR], 11.470; 95% confidence interval [CI], 4.283-30.721), nervous system disease (OR, 5.596; 95%CI, 2.445 to 12.809), developmental delay (OR, 5.157; 95% CI, 1.990-13.363), benzodiazepine (OR, 3.359; 95% CI 1.278-8.832), number of catheters (OR, 1.918; 95% CI, 1.425 to 2.582), and age (OR, 0.985; 95% confidence interval CI, 0.976-0.993). CONCLUSIONS: Delirium is a common complication in the PICU. The independent risk factors include mechanical ventilation, nervous system disease, developmental delay, benzodiazepines, higher number of catheters, and younger age. This study may help develop intervention strategies to reduce the incidence of delirium in critically ill children by targeting modifiable risk factors. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include paying attention to high-risk children in the ICU who are prone to delirium, removing influencing factors as soon as possible, and providing targeted nursing interventions.

Aflatoxin B1 causes oxidative stress and apoptosis in sheep testes associated with disrupting rumen microbiota.

Aflatoxin B1 (AFB1) is an unavoidable environmental pollutant commonly found in feed and foodstuffs. It is the most toxic one of all the aflatoxins, which can cause severe impairment to testicular development and function. Yet, the underlying mechanisms of reproductive toxicity in rams sheep remain inconclusive. The study was designed to explore the effects of AFB1 on sheep testes through rumen-microbiota, oxidative stress and apoptosis. Six-month-old male Dorper rams (n = 6) were orally administrated with 1.0 mg/kg AFB1 (dissolved in 20 mL 4% ethanol) 24 h before the experiment. At the same time, rams in the control group (n = 6) were intragastrically administrated with 20 mL 4% ethanol. It was observed that acute AFB1 poisoning had significant (p < 0.05) toxin residue in the testis and could cause testicular histopathological damage. AFB1 stimulated the secretion of plasma testosterone level through regulating testosterone synthesis-related genes (StAR, 3ß-HSD, CYP11A1, and CYP17A1), which are accompanied by the increase of oxidative stress and testicular apoptosis that had a close relationship with the regulation of testosterone secretion. Interestingly, we observed rumen dysbacteriosis and decreased the abundances of Prevotella, Succiniclasticum, CF231, Ruminococcus, and Pseudobutyrivibrio in AFB1-exposed sheep, which were negatively correlated to the testosterone synthesis-related gene levels. Taken together, our findings indicated that AFB1 induced testicular damage and testicular dysfunction, which is related to testicular oxidative stress and apoptosis involved in rumen dysbacteriosis in sheep.

Measuring Brown Fat Using MRI and Implications in the Metabolic Syndrome.

Metabolic syndrome is presently becoming a global health concern. Brown adipose tissue (BAT) has the potential for managing the risk factors of metabolic syndrome by adjusting plasma lipids and glucose. Magnetic resonance imaging (MRI) is a noninvasive and radiation-free imaging modality for BAT research and clinical applications in both animals and humans. In the past decade, MRI technologies for detecting and characterizing BAT have developed rapidly, with progress in MRI sequencing and the emerging understanding of BAT. In this review, we focus on the main MRI methods for BAT including currently used imaging techniques and new methods and their implications for the symptoms and complications of metabolic syndrome. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 2.

Population aging and trends of pulmonary tuberculosis incidence in the elderly.

BACKGROUND: To explore population aging and the epidemic trend of pulmonary tuberculosis (PTB) in the elderly, and provide a basis for the prevention and control of pulmonary tuberculosis among the elderly. METHODS: We collected clinical information of 239,707 newly active PTB patients in Shandong Province from 2005 to 2017. We analyzed and compared the clinical characteristics, reported incidence and temporal trend of PTB among the elderly group (≥60 years) and the non-elderly group (< 60 years) through logistic model and Join-point regression model. RESULTS: Among the total PTB cases, 77,192(32.2%) were elderly. Compared with non-elderly patients, newly active elderly PTB patients account for a greater proportion of male cases (OR 1.688, 95% CI 1.656-1.722), rural population cases (OR 3.411, 95% CI 3.320-3.505) and bacteriologically confirmed PTB cases (OR 1.213, 95%CI 1.193-1.234). The annual reported incidence of total, elderly, pulmonary bacteriologically confirmed cases were 35.21, 68.84, 35.63 (per 100,000), respectively. The annual reported incidence of PTB in the whole population, the elderly group and the non-elderly group has shown a slow downward trend since 2008. The joinpoint regression model showed that the overall reported incidence of PTB in the elderly significantly decreased from 2007 to 2017 (APC = -5.3, P < 0.05). The reported incidence of bacteriologically confirmed PTB among elderly patients declined rapidly from 2005 to 2014(2005-2010 APC = -7.2%, P < 0.05; 2010-2014 APC = -22.6%, P < 0.05; 2014-2017 APC = -9.0%, P = 0.1). The reported incidence of clinically diagnosed PTB among elderly patients from 2005 to 2017 (11.48-38.42/100,000) increased by about 235%. It rose significantly from 2007 to 2014 (APC = 9.4, P<0.05). CONCLUSIONS: Compared with the non-elderly population, the reported incidence of PTB in the elderly population is higher. The main burden of PTB will shift to the elderly, men, rural population, and clinically diagnosed patients. With the intensification of aging, more researches on elderly PTB prevention and treatment will facilitate the realization of the global tuberculosis (TB) control targets.

Homocysteine induced a calcium-mediated disruption of mitochondrial function and dynamics in endothelial cells.

Homocysteine (Hcy) is a sulfur-containing amino acid that originated in methionine metabolism and the elevated level of Hcy in plasma is considered to be an independent risk factor for cardiovascular diseases (CVD). Endothelial dysfunction plays a major role in the development of CVD, while the potential mechanism of Hcy-induced endothelial dysfunction is still unclear. Here, in Hcy-treated endothelial cells, we observed the destruction of mitochondrial morphology and the decline of mitochondrial membrane potential. Meanwhile, the level of ATP was reduced and the reactive oxygen species was increased. The expressions of dynamin-related protein 1 (Drp1) and phosphate-Drp1 (Ser616) were upregulated, whereas the expression of mitofusin 2 was inhibited by Hcy treatment. These findings suggested that Hcy not only triggered mitochondrial dysfunction but also incurred an imbalance of mitochondrial dynamics in endothelial cells. The expression of mitochondrial calcium uniporter (MCU) was activated by Hcy, contributing to calcium transferring into mitochondria. Interestingly, the formation of mitochondria-associated membranes (MAMs) was increased in endothelial cells after Hcy administration. The inositol 1,4,5-triphosphate receptor (IP3R)-glucose-regulated protein 75 (Grp75)-voltage-dependent anion channel (VDAC) complex, which was enriched in MAMs, was also increased. The accumulation of mitochondrial calcium could be blocked by inhibiting with the IP3R inhibitor Xestospongin C (XeC) in Hcy-treated cells. Then, we confirmed that the mitochondrial dysfunction and the increased mitochondrial fission induced by Hcy could be attenuated after Hcy and XeC co-treatment. In conclusion, Hcy-induced mitochondrial dysfunction and dynamics disorder in endothelial cells were mainly related to the increase of calcium as a result of the upregulated expressions of the MCU and the IP3R-Grp75-VDAC complex in MAMs.

The chemical diversity, the attractant, anti-acetylcholinesterase, and antifungal activities of metabolites from biocontrol Trichoderma harzianum uncovered by OSMAC strategy.

Eight new compounds (1-8) were discovered from Trichoderma harzianum associated with edible mushroom by the one strain many compounds (OSMAC) strategy. Triharzianin A (1) is the first naturally scaffold characterized by a C13-prostaglandin skeleton. The configurations of 1-3, and 5 were determined by the Mosher's method, experimental and calculated ECD spectra, and plausible biosynthesis of stereospecific epoxidation. Most compounds indicated obvious feeding attractant activities to silkworm with attraction rates at 30-90%. Compound 7 showed anti-acetylcholinesterase (anti-AChE) activity with a ratio of 29% at a concentration of 50 µM for insecticidal potential. So 2,​3-​dialkylchromone (7) had potential of chemical entrapment and killing of insects. Compounds 2, 3 and 7-11 showed antifungal activities against Aspergillus fumigates, and Trichoderma sp. from mushroom with MICs ≤ 300 µM. The four fermentation extracts also indicated obvious feeding attractant activities to silkworm for the activities brought by active metabolites from T. harzianum. The material base of biocontrol induced by the interaction of host-fungal symbiont can be investigated by the antifungal metabolites against pathogen fungi.

Association between body mass index and newly diagnosed drug-resistant pulmonary tuberculosis in Shandong, China from 2004 to 2019.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. METHODS: 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. RESULTS: Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726-0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049-1.730; adjusted OR (aOR) 1.31, 95% CI 1.017-1.686), P < 0.05. In addition, overweight were positively associated with MDR-TB (OR 1.603, 95% CI 1.002-2.566; aOR 1.639, 95% CI 1.02-2.633), isoniazid + rifampicin + streptomycin resistance (OR 1.948, 95% confidence interval (CI): 1.061-3.577; aOR 2.113, 95% CI 1.141-3.912), Any isoniazid + streptomycin resistance (OR 1.472, 95% CI 1.013-2.14; aOR 1.483, 95% CI 1.017-2.164), P < 0.05. CONCLUSIONS: The higher risk of MDR-TB, isoniazid + rifampicin + streptomycin resistance, Any isoniazid + streptomycin resistance, and co-morbidity among overweight population implies that routine screening for drug sensitivity and more attention on co-morbidity among overweight TB cases may be necessary. In addition, underweight TB cases have a higher risk of isoniazid resistance. Our study suggests that an in-depth study of the interaction between host metabolic activity and infection of DR-TB may contribute more to novel treatment options or preventive measures, and accelerate the implementation of the STOP TB strategy.

Aflatoxin B1 alters meat quality associated with oxidative stress, inflammation, and gut-microbiota in sheep.

Aflatoxin B1 (AFB1) is an unavoidable contaminant in animal feed and agricultural products. AFB1 has been found to impair the liver and kidney function of sheep. However, few data are available, which explain the toxic damage of AFB1 exposure on meat quality. In the study, male Dorper RAMS sheep (6-month-old) were orally administrated with AFB1 at the dose of 1 mg/kg body weight once. The body temperature, serum biochemistry, meat quality-related parameters, oxidation indicators in meat and serum, the mRNA expression of pro-inflammatory cytokines and anti-inflammatory, and microbiota composition of feces were measured 24 h after AFB1 exposure. The results showed that the body temperature was slightly increased, the mental state of mutton sheep was suppressed, and biochemical indicators were significantly changed after AFB1 exposure. AFB1 impaired mutton quality reflected by the structure of muscle fibers was changed, and increased muscle drip loss and lightness (L*), and decreased muscle redness (a*). Moreover, we found that AFB1 caused changes in the oxidative stress indicators T-SOD, T-AOC, MDA, GSH level, and GSH/GSSG ratio, and inflammation damage of mutton reflected by increasing pro-inflammatory TNF-α and reducing anti-inflammatory IL-10 mRNA levels, disrupts the secretion of inflammatory factors, and changed the composition of gut microbiota reflected by significantly increased Firmicutes/Bacteroidetes ratio and decreased the abundances of Butyrivibrio, which are related to the quality of the mutton. In summary, gut microbiota participates in AFB1 to damage mutton quality, which may be co-mediated by oxidative stress, inflammation, and gut microbiota.

Ambient air pollutants, diabetes and risk of newly diagnosed drug-resistant tuberculosis.

BACKGROUND: Drug-resistant tuberculosis (DR-TB), diabetes and exposure to air pollution are thought to be important threat to human health, but no studies have explored the effects of ambient air pollutants on DR-TB when adjusting diabetes status so far. METHODS: We performed a study among 3759 newly diagnosed TB cases with drug-susceptibility testing results, diabetes status, and individual air pollution data in Shandong from 2015 to 2019. Generalized linear mixed models (GLMM) including three models (Model 1: without covariates, Model 2: adjusted by diabetes status only, Model 3: with all covariates) were applied. RESULTS: Of 3759 TB patients enrolled, 716 (19.05%) were DR-TB, and 333 (8.86%) had diabetes. High exposure to O3 was associated with an increased risk of RFP-resistance (Model 2 or 3: odds ratio (OR) = 1.008, 95% confidence intervals (CI): 1.002-1.014), ethambutol-resistance (Model 3: OR = 1.015, 95%CI: 1.004-1.027) and any rifampicin+streptomycin resistance (Model 1,2,3: OR = 1.01, 95%CI: 1.002-1.018) at 90 days. In contrast, NO2 was associated with a reduced risk of DR-TB (Model 3: OR = 0.99, 95%CI: 0.981-0.999) and multidrug-resistant TB (MDR-TB) (Model 3: OR = 0.977, 95%CI: 0.96-0.994) at 360 days. Additionally, SO2 (Model 1, 2, 3: OR = 0.987, 95%CI: 0.977-0.998) showed a protective effect on MDR-TB at 90 days. PM2.5 (90 days, Model 2: OR = 0.991, 95%CI: 0.983-0.999), PM10 (360 days, Model 2: OR = 0.992, 95%CI: 0.985-0.999) had protective effects on any RFP+SM resistance. CONCLUSIONS: O3 contributed to an elevated risk of TB resistance but PM2.5, PM10, SO2, NO2 showed an inverse effect. Air pollutants may affect the development of drug resistance among TB cases by adjusting the status of diabetes.

The Cocultured Nigrospora oryzae and Collectotrichum gloeosporioides, Irpex lacteus, and the Plant Host Dendrobium officinale Bidirectionally Regulate the Production of Phytotoxins by Anti-phytopathogenic Metabolites.

The distinctive nature of the endophyte Irpex lacteus, host plant, and the phytopathogen Collectotrichum gloeosporioides resulted in both negative and positive regulation of the production of phytotoxins from Nigrospora oryzae. The coculture of nonhomologous I. lacteus and N. oryzae resulted in a greater number of anti-phytopathogenic metabolites from the dominant endophyte than the coculture of homologous I. lacteus and N. oryzae. The coculture of the phytopathogen N. oryzae and either the nonhomologous (isolation of I. lacteus and N. oryzae from the different plants) or homologous (isolation of I. lacteus and N. oryzae from the same plant) endophyte I. lacteus from different sources indicated that the nonhomologous I. lacteus grew faster than the homologous I. lacteus, and the production of phytotoxic azaphilone from the phytopathogenic N. oryzae decreased due to the inhibition resulting from being cocultured with nonhomologous I. lacteus. On the other hand, the production of phytotoxic azaphilone was promoted by the coculture of two phytopathogens, N. oryzae and C. gloeosporioides. The extract of the host plant, Dendrobium officinale, also increased anti-phytopathogenic metabolite production. Six new phytotoxic azaphilones from N. oryzae, four new tremulane sesquiterpenes from I. lacteus, and a new polyketone were isolated. The endophyte-phytopathogen, phytopathogen-phytopathogen, and endophyte-phytopathogen-host interactions can induce the chemical diversity of novel anti-phytopathogenic metabolites.

Association between economic development level and tuberculosis registered incidence in Shandong, China.

BACKGROUND: Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. METHODS: By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention. RESULTS: Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (<9772.8086 China Yuan(CNY); 9772.8086-33,835.5391 CNY; >33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are - 0.0015682, - 0.0028132 and - 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. CONCLUSION: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.

Inducing Intermediates in Biotransformation of Natural Polyacetylene and A Novel Spiro-γ-Lactone from Red Ginseng by Solid Co-Culture of Two Gut Chaetomium globosum and The Potential Bioactivity Modification by Oxidative Metabolism.

The ω-hydroxyl-panaxytriol (1) and ω-hydroxyl-dihydropanaxytriol (2)-are rare examples of polyacetylene metabolism by microbial transformation, and these new metabolites (1, 2) from fermented red ginseng (FRG) by solid co-culture induction of two Chaetomium globosum should be the intermediates of biotransformation of panaxylactone (metabolite A). The metabolic pathway of panaxylactone was also exhibited. The ingredients of red ginseng (RG) also induced the production of rare 6/5/5 tricyclic ring spiro-γ-lactone skeleton (3). The ω-hydroxylation of new intermediates (1, 2) decreases cytotoxicity and antifungal activity against C. globosum compared with that of its bioprecursor panaxytriol. Additionally, compounds 1 and 2 indicated obvious inhibition against nitric oxide (NO) production, with ratios of 44.80 ± 1.37 and 23.10 ± 1.00% at 50 µM. 1 has an equivalent inhibition of NO production compared with the positive drug. So, the microbial biotransformation that occurred in FRG fermented by gut C. globosum can change the original bioactivity of polyacetylene, which gave a basis about the metabolic modification of red ginseng by intestinal fungus fermentation.

Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018.

BACKGROUND: Primary drug-resistant tuberculosis (DR-TB) has contributed to a significant health and economic burden on a global scale, especially in China. we sought to estimate epidemiological characteristics of primary DR-TB in China from 2004 to 2018. METHODS: Eleven thousand four hundred sixty-seven newly diagnosed and 1981 retreated TB cases with drug susceptibility data were included. Chi-Square test for trends, linear regression, a joinpoint regression model and temporal trend in proportions of the different resistance patterns were carried out. RESULTS: The proportion of primary DR-TB and mono-resistant TB (MR-TB) in China had reduced by more than 12% since 2004, and were 21.38%, 13.35% in 2018 respectively. Among primary DR-TB cases (2173,18.95%), the percentage of multiresistant TB (MDR-TB, from 5.41 to 17.46%), male (from 77.03 to 84.13%), cavity (from 13.51 to 43.92%), rifampicin(RFP)-resistant TB (from 8.11 to 26.98%), streptomycin(SM)-resistant TB (from 50.00 to 71.43%) increased significantly (P < 0.05). On the contrary, the proportion of female, non-cavity, isoniazide(INH)-resistant TB (from 55.41 to 48.15%) and MR-TB (from 82.43 to 62.43%) decreased significant (P < 0.05). The primary drug resistance rate among female, cavity, smoking, drinking, 15 to 44 year-old TB subgroups increased by 0.16, 6.24, 20.95, 158.85, 31.49%, respectively. The percentage of primary DR-TB, RFP-resistant TB dropped significantly during 2004-2007 in Joinpoint regression model. CONCLUSION: The total rate of drug resistance among new TB cases showed a downward trend in Shandong, China, from 2004 to 2018. Primary drug resistance patterns were shifting from female, non-cavity, INH-resistant TB, and MR-TB groups to male, cavity, RFP/SM-resistant TB, and MDR-TB groups. Considering the rising drug resistance rate among some special population, future control of primary DR-TB in China may require an increased focus on female, cavity, smoking, drinking, or 15 to 44 year-old TB subgroups.

A Safe and Efficient Strategy for the Rapid Elimination of Blood Lead In†Vivo Based on a Capture-Fix-Separate Mechanism.

Lead poisoning is an important problem because of its serious effects on human health. Yet a solution is not available due to an incomplete understanding of the state of lead ions in blood. Since most blood lead binds to hemoglobin (Hb) in red blood cells, identifying and capturing lead-contaminated Hb in RBCs is important. Herein, a magnetic blood lead remover with hyperbranched poly(amidoamine)s (HPAM) as template/co-adsorbent and core-shell mesoporous structure was synthesized. Lead-containing Hb was selectively captured and then fixed by mesoporous channels. The magnetic separation technology was used to separate the magnetic remover from blood. A related blood lead clean-up apparatus was used to remove lead from the blood of a pig in vivo. Results of physical/chemical characterizations, biocompatibility experiments, animal tests, and theoretical simulation verify the safety and efficiency of this removal strategy and the high efficiency of the blood lead clean-up apparatus.