Metal-Organic Framework Based Sensors for Benzene Vapor.

Sensing of benzene vapor is a hot spot due to the volatile drastic carcinogen even at trace concentration. However, achieving convenient and rapid detection is still a challenge. As a sort of functional porous material, metal-organic frameworks (MOFs) have been developed as detection sensors by adsorbing benzene vapor and converting it into other signals (fluorescence intensity/wavelength, chemiresistive, weight or color, etc.). Supramolecular interaction between benzene molecules and the host framework, aperture size/shape and structural flexibility are influential factors in the performance of MOF-based sensors. Therefore, enhancing the host-guest interactions between the host framework and benzene molecules, or regulating the diffusion rate of benzene molecules by changing the aperture size/shape and flexibility of the host framework to enhance the detection signal are effective strategies for constructing MOF-based sensors. This concept highlights several types of MOF-based sensors for the detection of benzene vapor.

[Zi Huangjing TM Preparation Relieves Cancer-Related Fatigue During Chemotherapy: A Prospective Single-Arm Multicenter Clinical Trial].

Objective: To primarily explore the efficacy of Zi Huangjing TM preparation in patients with cancer-related fatigue (CRF) during chemotherapy. Methods: This study was designed as a prospective, single-arm, multicenter clinical trial. According to the plan of the study, patients with malignant tumors who had received at least one cycle of chemotherapy and had moderate-to-severe CRF (Piper Fatigue Scale score≥4) were enrolled. All the enrolled patients took Zi Huangjing TM preparation (2.1 g, twice a day) every day during the two subsequent cycles of chemotherapy and were followed up. During the period, the enrolled patients independently completed the Piper Fatigue Scale and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale, and part of their biochemical and immunological indicators were measured at the baseline, before the second cycle of chemotherapy (day 21), and before the third cycle of chemotherapy (day 42). The primary endpoint was the change in Piper Fatigue Scale scores between the baseline and day 42. Results: Eventually, 47 patients completed the entire study. After treatment, the mean score of the Piper Fatigue Scale assessed before the third cycle of chemotherapy (day 42) was 3.21±1.67, which was significantly lower than that at baseline (5.89±1.36) ( P=0.000), and the patients' CRF was significantly improved. In terms of quality of life, the patient's global quality of life, physical functions, role function, emotional function, cognitive function, and social function were significantly improved. In terms of symptom management, the patient's symptoms, such as fatigue, nausea and vomiting, insomnia, and appetite loss also significantly improved. No severe adverse reactions (grades 3 and 4) occurred during the observation period of this study. After evaluation, the adverse reactions that the patients actually had were considered to be related to chemotherapy, but unrelated to Zi Huangjing TM preparation. Conclusion: According to our preliminary investigation, Zi Huangjing TM preparation is safe and has the potential therapeutic effect of improving CRF in cancer patients during chemotherapy. However, further larger-scale randomized controlled clinical studies are needed to confirm the efficacy of Zi Huangjing TM in improving CRF.

Integrative Analyses Followed by Functional Characterization Reveal TMEM180 as a Schizophrenia Risk Gene.

Recent large-scale integrative analyses (including Transcriptome-Wide Association Study [TWAS] and Summary-data-based Mendelian Randomization [SMR]) have identified multiple genes whose cis-regulated expression changes may confer risk of schizophrenia. Nevertheless, expression quantitative trait loci (eQTL) data and genome-wide associations used for integrative analyses were mainly from populations of European ancestry, resulting in potential missing of pivotal biological insights in other continental populations due to population heterogeneity. Here we conducted TWAS and SMR integrative analyses using blood eQTL (from 162 subjects) and GWAS data (22 778 cases and 35 362 controls) of schizophrenia in East Asian (EAS) populations. Both TWAS (P = 2.89 × 10-14) and SMR (P = 6.04 × 10-5) analyses showed that decreased TMEM180 mRNA expression was significantly associated with risk of schizophrenia. We further found that TMEM180 was significantly down-regulated in the peripheral blood of schizophrenia cases compared with controls (P = 8.63 × 10-4 in EAS sample), and its expression was also significantly lower in the brain tissues of schizophrenia cases compared with controls (P = 1.87 × 10-5 in European sample from PsychENCODE). Functional explorations suggested that Tmem180 knockdown affected neurodevelopment, ie, proliferation and differentiation of neural stem cells. RNA sequencing showed that pathways regulated by Tmem180 were significantly enriched in brain development and synaptic transmission. In conclusion, our study provides convergent lines of evidence for the involvement of TMEM180 in schizophrenia, and highlights the potential and importance of resource integration and sharing at this big data era in bio-medical research.

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Functional Genomics Identify a Regulatory Risk Variation rs4420550 in the 16p11.2 Schizophrenia-Associated Locus.

BACKGROUND: Genome-wide association studies (GWASs) have reported hundreds of genomic loci associated with schizophrenia, yet identifying the functional risk variations is a key step in elucidating the underlying mechanisms. METHODS: We applied multiple bioinformatics and molecular approaches, including expression quantitative trait loci analyses, epigenome signature identification, luciferase reporter assay, chromatin conformation capture, homology-directed genome editing by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/Cas9), RNA sequencing, and ATAC-Seq (assay for transposase-accessible chromatin using sequencing). RESULTS: We found that the schizophrenia GWAS risk variations at 16p11.2 were significantly associated with messenger RNA levels of multiple genes in human brain, and one of the leading expression quantitative trait loci genes, MAPK3, is located ∼200 kb away from these risk variations in the genome. Further analyses based on the epigenome marks in human brain and cell lines suggested that a noncoding single nucleotide polymorphism, rs4420550 (p = 2.36 × 10-9 in schizophrenia GWAS), was within a DNA enhancer region, which was validated via in vitro luciferase reporter assays. The chromatin conformation capture experiment showed that the rs4420550 region physically interacted with the MAPK3 promoter and TAOK2 promoter. Precise CRISPR/Cas9 editing of a single base pair in cells followed by RNA sequencing further confirmed the regulatory effects of rs4420550 on the transcription of 16p11.2 genes, and ATAC-Seq demonstrated that rs4420550 affected chromatin accessibility at the 16p11.2 region. The rs4420550-[A/A] cells showed significantly higher proliferation rates compared with rs4420550-[G/G] cells. CONCLUSIONS: These results together suggest that rs4420550 is a functional risk variation, and this study illustrates an example of comprehensive functional characterization of schizophrenia GWAS risk loci.

Recent Positive Selection Drives the Expansion of a Schizophrenia Risk Nonsynonymous Variant at SLC39A8 in Europeans.

Natural selection has played important roles in optimizing complex human adaptations. However, schizophrenia poses an evolutionary paradox during human evolution, as the illness has strongly negative effects on fitness, but persists with a prevalence of ~0.5% across global populations. Recent studies have identified numerous risk variations in diverse populations, which might be able to explain the stable and high rate of schizophrenia morbidity in different cultures and regions, but the questions about why the risk alleles derived and maintained in human gene pool still remain unsolved. Here, we studied the evolutionary pattern of a schizophrenia risk variant rs13107325 (P < 5.0 × 10(-8) in Europeans) in the SLC39A8 gene. We found the SNP is monomorphic in Asians and Africans with risk (derived) T-allele totally absent, and further evolutionary analyses showed the T-allele has experienced recent positive selection in Europeans. Subsequent exploratory analyses implicated that the colder environment in Europe was the likely selective pressures, ie, when modern humans migrated "out of Africa" and moved to Europe mainland (a colder and cooler continent than Africa), new alleles derived due to positive selection and protected humans from risk of hypertension and also helped them adapt to the cold environment. The hypothesis was supported by our pleiotropic analyses with hypertension and energy intake as well as obesity in Europeans. Our data thus provides an intriguing example to illustrate a possible mechanism for maintaining schizophrenia risk alleles in the human gene pool, and further supported that schizophrenia is likely a product caused by pleiotropic effect during human evolution.

Bleeding after bevacizumab treatment in patients with metastatic colorectal cancer.

AIMS AND BACKGROUND: To evaluate the adverse events (AEs) of bleeding caused by bevacizumab/5-fluorouracil/leucovorin (5-FU/LV) combination chemotherapy with addition of irinotecan or oxaliplatin in patients with metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted to evaluate the bleeding AEs associated with bevacizumab and to explore potential associations between bleeding and baseline patient characteristics. The National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 were used to classify the severity of AEs. AEs were divided into five grades: grade 1, mild: intervention not indicated; grade 2, moderate: medical intervention or minor cauterization indicated; grade 3, severe: transfusion, radiological, endoscopic or elective surgical intervention indicated; grade 4, life threatening: urgent intervention indicated; and grade 5, death. RESULTS: Sixty-two patients were evaluated. Bleeding occurred in 26 (41%) patients; the incidence of grade 3 bleeding was 1.6% while no grade 4-5 bleeding occurred. Grade 1 epistaxis and grade 2 hemoptysis events were observed in 25.8% and 3.2% of patients, respectively. Hematochezia events occurred in 12 (19.4%) patients, one (1.6%) of whom required bevacizumab discontinuation. The incidence of hematochezia was higher in patients with unresected primary tumors, prior intestinal bleeding, and tumor response (p<0.05). CONCLUSIONS: These data provide important information about the incidence of clinically significant bleeding AEs, including minor mucocutaneous hemorrhage and major tumor-related bleeding such as hemoptysis and hematochezia in bevacizumab-treated mCRC patients. In addition, unresected primary tumor, prior bleeding, and tumor response were significant risk factors for hematochezia.

Failure of replicating the association between hippocampal volume and 3 single-nucleotide polymorphisms identified from the European genome-wide association study in Asian populations.

Hippocampal volume is a key brain structure for learning ability and memory process, and hippocampal atrophy is a recognized biological marker of Alzheimer's disease. However, the genetic bases of hippocampal volume are still unclear although it is a heritable trait. Genome-wide association studies (GWASs) on hippocampal volume have implicated several significantly associated genetic variants in Europeans. Here, to test the contributions of these GWASs identified genetic variants to hippocampal volume in different ethnic populations, we screened the GWAS-identified candidate single-nucleotide polymorphisms in 3 independent healthy Asian brain imaging samples (a total of 990 subjects). The results showed that none of these single-nucleotide polymorphisms were associated with hippocampal volume in either individual or combined Asian samples. The replication results suggested a complexity of genetic architecture for hippocampal volume and potential genetic heterogeneity between different ethnic populations.

[Optimized cultivation of a bioflocculant M-C11 produced by Klebsiella pneumoniae and its application in sludge dewatering].

A bioflocculant-producing Klebsiella pneumoniae strain C11 was screened out from activated sludge and the optimal medium conditions for the production of microbial flocculant M-C11 were determined. The bioflocculant was used in activated sludge dewatering and compared with conventional chemical conditioners. Effects of pH, CaCl2 dosages and M-C11 dosages on sludge dewaterability were investigated. The optimized conditions for M-C11 production indicated that the optimal medium carbon, nitrogen, metal ion were 30 g x L(-1) glucose, 2 g x L(-1) NaNO3 and 0.5 g x L(-1) MgSO4, respectively. The flocculating rate with kaolin suspension was as high as 91.70%, when incubated in a rotary shaker at 150 r x min(-1) and 37 degrees C for 48 h. The microbial focculant showed excellent pH and thermal stability over a pH range of 4-8 and a temperature range of 20-60 degrees C. Then the bioflocculant M-C11 produced by Klebsiella pneumoniae was employed to enhance the sludge dewaterability. The sludge resistance to filtration (SRF) and cake moisture decreased from 11.64 x 10(12) m x kg(-1) and 98.86% to 4.66 x 10(12) m x kg(-1) and 83.74%, respectively. Sludge dewatering performance was more significantly improved with the optimal conditioning dosages (pH = 6, 3 mL M-C11, 4 mL CaCl2), than inorganic flocculating reagents such as aluminum sulfate and polymeric aluminum chloride (PAC). The microbial flocculant has advantages over traditional sludge conditioners for its lower cost, benign biodegradability and ignorable secondary pollution. In addition, it was favorably adapted to the sludge pH and salinity. The novel bioflocculant could be used as a potential conditioner for sludge dewatering.

[Sludge dewaterability with combined conditioning using Fenton's reagent and CPAM].

The moisture of sludge significantly influenced its dewaterability and the disposal cost. Cationic polyacrylamide (CPAM) and Fenton's reagent were investigated for sludge dewatering with separate and combined conditioning. Several parameters were used to evaluate the dewatering performance and to analyze the conditioning mechanism, such as cake moisture, soluble COD, protein and polysaccharide contents in supernatant and sludge particle size. The results indicated that favorable dewaterability was achieved when the sludge was conditioned at higher CPAM degrees, and sludge dewatering ability was further improved at acidic conditions. In Fenton reaction, higher H2O2 dosages enhanced the dewatering performance of sludge. Combined conditioning using Fenton's reagent and CPAM led to considerable improved sludge dewaterability. At the optimized dosages of FeSO4 (2 g x L(-1)) and H2O2 (6 g x L(-1)), the sludge moisture declined to 76.7% from 85.5% (raw sludge), while a moisture as low as 74.8% was obtained by combined conditioning using CPAM (3 kg x t(-1)). Sludge particle size went down and the specific surface area grew bigger after Fenton reaction. As a result of disintegration of extracellular polymeric substances (EPS), the adsorbed and intrinsic water were released from microorganisms and sludge flocs. CPAM addition remarkably promoted the coagulating and flocculating of dispersed flocs. Sludge particle size changed from 35.16 microm to 50.50 microm, and the specific surface area declined from 0.39 m2 x g(-1) to 0.20 m2 x g(-1). The combined conditioning using Fenton's reagent and CPAM was proved to be more effective in improving sludge dewaterability, compared with the separate conditioning.

Understanding the role of mitochondria in the pathogenesis of chronic pain.

Chronic pain is a major public health problem. Mitochondria play important roles in a myriad of cellular processes and mitochondrial dysfunction has been implicated in multiple neurological disorders. This review aims to provide an insight into advances in understanding of the role of mitochondrial dysfunction in the pathogenesis of chronic pain. The results show that the five major mitochondrial functions (the mitochondrial energy generating system, reactive oxygen species generation, mitochondrial permeability transition pore, apoptotic pathways and intracellular calcium mobilisation) may play critical roles in neuropathic and inflammatory pain. Therefore, protecting mitochondrial function would be a promising strategy to alleviate or prevent chronic pain states. Related chronic inflammatory and neuropathic pain models, as well as the spectral characteristics of current fluorescent probes to detect mitochondria in pain studies, are also discussed.

[Investigation of HIV and syphilis infection and AIDS-related behaviors among money boys, in Guangzhou, China].

OBJECTIVE: To explore the HIV and syphilis infection and AIDS-related behaviors among money boys (MB) in Guangzhou. METHODS: A total of 152 subjects were recruited from MB gathering place (clubs, parks, Internet etc.) by a local NGO. Of which, 151 individuals completed the investigation and blood sample collection. An anonymous face to face interview were used to obtain data of AIDS-related behavior, knowledge and attitudes. Venous blood samples were collected for HIV and syphilis antibody test. χ(2) test were used to compare the characteristics of HIV and syphilis infection subjects and P < 0.05 was counted as significant. RESULTS: HIV and current syphilis infection rate were 11.3% (17/151) and 19.9% (30/151), respectively. Among the subjects, 47.0% (71/151) had unprotected anal intercourse (UAI) with commercial male sex partners, 43.7% (66/151) had UAI with non-commercial male sex partners in the past six month. 85.4% (129/151) were aware of AIDS-related knowledge, while 34.4% (52/151) thought they have no risk of HIV infection, 24.5% (37/151) didn't know the prevalence of HIV among MSM in China, and 55.0% (83/151) had no idea of HIV prevalence or thought HIV prevalence was not serious at all among MB. MB who had experienced sex after drunk/used drugs had higher proportion of syphilis infection (33.3% vs 16.5%; χ(2) = 4.26, P = 0.039), and who had ever been experiencing condom broken during sex had much higher syphilis infection rate than those didn't (36.7% vs 15.7%; χ(2) = 6.64, P = 0.010). A multi-Logistics regression analysis showed that subjects had ever been experiencing condom broke during sex in the past six month were associated with syphilis infection (χ(2) = 6.24, P = 0.012; OR = 3.11, 95%CI = 1.28 - 7.57). CONCLUSION: Money boys have high prevalence of HIV and syphilis infection. They are lack of perception of HIV risk and active in unsafe sex behavior.

[Comparing patients' quality of life after phacoemulsification with intraocular lens implantation with that after extracapsular cataract extraction with intraocular lens implantation].

OBJECTIVE: To Compare the effects of phacoemulsification with intraocular lens implantation (PHACO + IOL) to extracapsular cataract extraction with intraocular lens implantation (ECCE + IOL) on quality of life. METHODS: The study population consisted of 116 patients receiving PHACO + IOL and 93 patients receiving ECCE + IOL. They were interviewed using the quality of life questionnaire, and the clinical outcomes were obtained before surgery and in 1 week, 1 month, 3 months after surgery respectively. RESULTS: Patients receiving PHACO + IOL reported larger benefit in quality of life and all sub-scales than did those receiving ECCE + IOL in 1 week after surgery. Subjects underwent PHACO + IOL showed better improvement in quality of life and two sub-scales (social and mental) than did those underwent ECCE + IOL in 1 month and 3 months after surgery. However, the improvement in other two sub-scales (self-care and mobility) was similar between two surgical groups in 1 month and 3 months after surgery. CONCLUSION: The patients receiving PHACO + IOL reported better and more rapid improvement in quality of life within 3 months after surgery. PHACO + IOL and ECCE + IOL have the same effects on improvement in self-care and mobility. So quality of life in patients receiving PHACO + IOL are better than those of ECCE + IOL.