Search

Background: Immune checkpoint inhibitors (ICIs) have significantly changed the current approach to cancer treatment. Although the use of ICIs has become the standard of care for advanced melanoma, reports of ICI use among Asian populations with melanoma are limited. Therefore, we conducted this retrospective study to assess the efficacy and safety of ICI use in Taiwanese patients.Patients: Patients with histologically confirmed melanoma treated with ICIs at Linkou Chang Gung Memorial Hospital from January 2014 to July 2019 were retrospectively reviewed. Univariant and multivariant analyses were performed to identify possible prognostic factors.Results: Among 80 patients, 45 were treatment-naïve (56.3%), and 35 received prior systemic drugs other than ICIs. Regarding treatment regimens, patients were treated with ipilimumab (n = 9), nivolumab (n = 33), pembrolizumab (n = 16), or combination drugs (n = 22). Nine patients achieved either a complete (n = 2) or partial (n = 7) response and 13 patients were stable, with a resulting response rate of 11.3% and disease control rate of 27.5%. As of the last follow-up in January 2020, patients treated with combination drugs had longer median progression-free survival (PFS) of 5.6 (95% confidence interval [CI]: 1.6–9.6) months than nivolumab (2.9 months, 95% CI: 1.9–3.9 months), pembrolizumab (3.2 months, 95% CI: 2.6–3.8 months), and ipilimumab (2.6 months, 95% CI: 2.4–2.8 months; p = 0.011). No significant differences in overall survival (OS) among the four regimens (p = 0.891) were noted. In the multivariate analysis, combination treatment, disease control, and performance ≤ 1 were independent prognostic factors for PFS. Liver metastases and no disease control were independent unfavorable prognostic factors for OS. The most common factor was skin toxicity (45%), followed by endocrine toxicity (18.8%). Patients undergoing combination treatment experienced more frequent and serious adverse events than patients undergoing monotherapy.Conclusion: ICIs demonstrated efficacy and safety in Taiwanese patients with melanoma. Combination treatment showed the greatest efficacy, but this was also accompanied by greater toxicity among the four regimens. In addition, we identified important prognostic factors, such as liver metastases, performance status, and tumor response, for both PFS and OS. These findings could provide physicians with more information to justify clinical outcomes observed in Asian patients with advanced melanoma.

Many Gram-negative bacterial pathogens utilize the type III secretion system (T3SS) to inject virulence factors, named effectors, into host cells. These T3SS effectors manipulate host cellular signaling pathways to facilitate bacterial pathogenesis. Death receptor signaling plays an important role in eukaryotic cell death pathways. NleB from enteropathogenic Escherichia coli (EPEC) and SseK1/3 from Salmonella enterica serovar Typhimurium (S. Typhimurium) are T3SS effectors. They are defined as a family of arginine GlcNAc transferase to modify a conserved arginine residue in the death domain (DD) of the death receptor TNFR and their corresponding adaptors to hijack death receptor signaling. Here we identified that these enzymes, NleB, SseK1, and SseK3 could catalyze auto-GlcNAcylation. Residues, including Arg13/53/159/293 in NleB, Arg30/158/339 in SseK1, and Arg153/184/305/335 in SseK3 were identified as the auto-GlcNAcylation sites by mass spectrometry. Mutation of the auto-modification sites of NleB, SseK1, and SseK3 abolished or attenuated the capability of enzyme activity toward their death domain targets during infection. Loss of this ability led to the increased susceptibility of the cells to TNF- or TRAIL-induced cell death during bacterial infection. Overall, our study reveals that the auto-GlcNAcylation of NleB, SseK1, and SseK3 is crucial for their biological activity during infection.

Ethnopharmacological RelevanceDiarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrheal disease and Pulsatilla decoction (PD), a TCM, has been found effective against DHD.ObjectiveThe aim of this study was to clarify the mechanism of action of PD in DHD using an untargeted lipidomics strategy.Materials and MethodsWistar rats were randomized to four groups, including the control group, model group, PD groups and self-healing group. The PD groups were given a daily intragastric gavage of PD at doses of 3.76 g/kg. The rat model of DHD established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment, drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of DHD. Then the clinical symptoms and signs, blood routine, serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed to evaluate DHD model and therapeutic effect of PD. Lipid biomarkers of DHD were selected by comparing the control and model groups with the colon lipidomics technology and an ultra-high performance liquid chromatography (UHPLC) coupled with Q Exactive plus mass analyzer. Multivariate statistical analysis and pattern recognition were employed to examine different lipids within the colon of PD-treated rats.ResultsThe clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of DHD. After treatment with PD, the clinical symptoms and signs of the rats with DHD were improved; the indexes of blood routine and inflammatory cytokines levels tended to be normal. The lipidomics profile of the model group were evidently disordered when compared to the control group. A total of 42 significantly altered lipids between the model-control groups were identified by multivariate statistical analysis. DHD may result from such lipid disorders which are related to glycerophospholipid metabolism, arachidonic acid (AA) metabolism, and sphingolipid metabolism. After PD treatment, the lipidomic profiles of the disorders tended to recover when compared to the model group. Twenty lipid molecules were identified and some glycerophospholipids and AA levels returned close to the normal level.ConclusionGlycerophospholipid metabolism may play an important role in the treatment of dampness-heat induced diarrhea using PD.

The acidulant is widely used in the production of animal husbandry, and its use is affected by many factors, including environmental factors, dosage, diet composition, and animal’s own factors, so only the correct use of the acidulant can bring good results in animal production and financial income. This article takes acidifier as an example to study the application of compound chemical treatment in livestock farms. In this paper, the effect of using acidulant in the first 1 to 3 weeks after early weaning of piglets is obvious through this experimental study. The effect gradually decreases after 3 weeks and basically has no effect after 4 weeks. Experimental studies have found that the combination of organic acids, antibiotics, and high copper is the most effective. These three have different functions and have complementary or additive effects. Under harsh feeding conditions, especially when the environmental sanitation and environmental conditions are relatively poor, the effect of acidulants is better than good feeding conditions. Experimental data show that fulvic acid depletes milk’s somatic cells in a short period of time and then quickly activates immune function, which is indicated by the increase in lymphocytes in the blood. When a large number of somatic cells migrate to the breast, the somatic cells in milk will also increase, thereby improving the immunity mediated by human cells. The experimental results show that the BFA formula added 1% to the cattle feed. After the research control of this experiment, the milk output increased by 9–17%, and the quality milk output increased by 19.12%, so the use of acidulant increased feed compensation and reduces gastrointestinal diseases and the reproduction of microorganisms in the rumen of dairy cows.

Abstract Background Drugs that inhibit the MEK/ERK pathway have therapeutic benefit in bladder cancer treatment but responses vary with patients, for reasons that are still not very clear. Interferon-α (IFN-α) is also used as a therapeutic agent for bladder cancer treatment but the response rate is low. It was found that IFN-α could enhance the cytotoxic effect of MEK inhibition. However, the potential mechanisms of that are still unclear. Understanding of the cross-talk between the IFN-α and MEK/ERK pathway will help enhance the efficacy of IFN-α or MEK inhibitors on bladder cancer. Methods Immunoprecipitation and pull-down assay were used to reveal the formation of signaling complex. The protein expressions were detected by western blot and immunohistochemistry. The cAMP level, Phosphodiesterase 4D (PDE4D) activity and Prostaglandin E2 (PGE2) concentration in cells, serum and tissues were detected by enzyme-linked immunosorbent assay. The role of PDE4D in bladder tumorigenesis in vivo was examined by the xenograft model. Tissue microarray chips were used to investigate the prognostic roles of PDE4D and tumor progression locus 2 (TPL2) in bladder cancer patients. Results IFN-α down-regulated the cyclooxygenase-2 (COX-2) expression in bladder cancer cells through the inhibition of TPL2/NF-κB pathway; IFN-α also inhibited COX-2 expression by suppressing cAMP signaling through TPL2-ERK mediated PDE4D activity. Reduction of the intracellular cAMP level by PDE4D potentiated the antitumor effect of IFN-α against bladder cancer in vitro and in vivo. Further analysis of clinical samples indicated that low PDE4D expression and high level of TPL2 phosphorylation were correlated to the development and poor prognosis in bladder cancer patients. Conclusions Our data reveal that IFN-α can exert its antitumor effect through a non-canonical JAK-STAT pathway in the bladder cancer cells with low activity of IFN pathway, and the TPL2 inhibition is another function of IFN-α in the context of bladder cancer therapy. The antitumor effects of IFN-α and MEK inhibition also depend on the PDE4D-mediated cAMP level in bladder cancer cells. Suppression of the TPL2 phosphorylation and intracellular cAMP level may be possible therapeutic strategies for enhancing the effectiveness of IFN-α and MEK inhibitors in bladder cancer treatment.

Abstract Background Molybdenum (Mo) is an essential micronutrient for almost all biological systems, which holds key positions in several enzymes involved in carbon, nitrogen and sulfur metabolism. In general, this transition metal needs to be coordinated to a unique pterin, thus forming a prosthetic group named molybdenum cofactor (Moco) at the catalytic sites of molybdoenzymes. The biochemical functions of many molybdoenzymes have been characterized; however, comprehensive analyses of the evolution of Mo metabolism and molybdoproteomes are quite limited. Results In this study, we analyzed almost 5900 sequenced organisms to examine the occurrence of the Mo utilization trait at the levels of Mo transport system, Moco biosynthetic pathway and molybdoproteins in all three domains of life. A global map of Moco biosynthesis and molybdoproteins has been generated, which shows the most detailed understanding of Mo utilization in prokaryotes and eukaryotes so far. Our results revealed that most prokaryotes and all higher eukaryotes utilize Mo whereas many unicellular eukaryotes such as parasites and most yeasts lost the ability to use this metal. By characterizing the molybdoproteomes of all organisms, we found many new molybdoprotein-rich species, especially in bacteria. A variety of new domain fusions were detected for different molybdoprotein families, suggesting the presence of novel proteins that are functionally linked to molybdoproteins or Moco biosynthesis. Moreover, horizontal gene transfer event involving both the Moco biosynthetic pathway and molybdoproteins was identified. Finally, analysis of the relationship between environmental factors and Mo utilization showed new evolutionary trends of the Mo utilization trait. Conclusions Our data provide new insights into the evolutionary history of Mo utilization in nature.

Background: We evaluated the prognostic factors of metastatic testicular non-seminomatous germ cell tumor (NSGCT) after chemotherapy. Materials and methods: Data from 20 metastatic testicular NSGCT patients were retrospectively collected between January 2002 and December 2015. The evaluation of prognostic factors included age, pulmonary metastasis, cancer stage, International Germ Cell Cancer Collaborative Group (IGCCCG) classification, and histology. Results: Twelve (60%) and eight (40%) patients had stage 2 and 3 disease, respectively. Good, intermediate, and poor prognoses were ten, six, and four patients, respectively. Eight patients (40%) were aged above 30 years at detection of testicular; cancer, and seven patients (35%) had pulmonary metastases. Sixteen patients had mixed germ cell tumors (MGCTs) only, Four were unfavorable histology (two MGCTs with choriocarcinoma-predominant, one pure choriocarcinoma and MGCTs with embryonal rhabdomyosarcoma transformation). Thirteen patients (65%) showed no evidence of disease (NED), and 7 patients (35%) that did not survive post therapy. Pulmonary metastases (P = 0.02), unfavorable histology (P = 0.007) were found to be prognostic factors of NED in patients with metastatic testicular NSGCTs. Age (P = 0.06) and stage (P = 0.06) showed considerable trend of significance. But risk group of IGCCCG exhibited no significant difference (P = 1). Conclusion: The presence of pulmonary metastases, and unfavorable histology but not GCCCG classification were associated with poor prognosis in in patients with metastatic testicular NSGCTs. Prognostic reclassification for IGCCCG groups is suggested from our study. Keywords: Testis, Non-seminomatous germ cell tumor, Age, Pulmonary metastasis, Prognostic factors, No evidence of disease

Abstract Background Iron accumulation in basal ganglia accompanies neuronal loss in Huntington’s disease (HD) patients and mouse disease models. Disruption of HD brain iron homeostasis occurs before the onset of clinical signs. Therefore, investigating the mechanism of iron accumulation is essential to understanding its role in disease pathogenesis. Methods N171-82Q HD transgenic mice brain iron was detected by using Diaminobenzidine-enhanced Perls’ stain. Iron homeostatic proteins including iron response protein 1 (IRP1), transferrin (Tf), ferritin and transferrin receptor (TfR) were determined by using western blotting and immunohistochemistry, and their relative expression levels of RNA were measured by RT-PCR in both N171-82Q HD transgenic mice and HEK293 cells expressing N-terminal of huntingtin. Results Iron was increased in striatum and cortex of N171-82Q HD transgenic mice. Analysis of iron homeostatic proteins revealed increased expression of IRP1, Tf, ferritin and TfR in N171-82Q mice striatum and cortex. The same results were obtained in HEK293 cells expressing N-terminal of mutant huntingtin containing 160 CAG repeats. Conclusion We conclude that mutant huntingtin may cause abnormal iron homeostatic pathways by increasing IRP1 expression in Huntington’s disease, suggesting potential therapeutic target.

A study has been conducted based on the drilling data and geochemical data from the Y1 Well in Chengkou of Northeastern Chongqing, including total organic carbon (TOC), kerogen microcomponent, equivalent vitrinite reflectance (Ro) and carbon isotope composition, which are the organic geochemistry characteristics of Wufeng-Longmaxi Formation shale. The characteristics of shale gas accumulation were determined by analyzing the microstructure, homogenization temperature and laser Raman data of fluid inclusions in the shale. Results show that carbonaceous shale is well developed in Upper Ordovician Wufeng Formation and Lower Silurian Longmaxi Formation in the Y1 Well. Organic-rich shale (TOC>2%) has a thickness up to 83 m. The kerogen type of the samples is mainly TypeⅠ, belonging to the moisture hydrocarbon generation stage. Numerous hydrocarbon inclusions and hydrocarbon-rich brine inclusions with methane gas in the fractured veins of shale indicate that the shale of Wufeng Formation-Longmaxi Formation in the Chengkou area has been supplied with sufficient shale gas. The associated brine inclusions with high homogenization temperature and high salinity indicate good preservation conditions during the shale gas accumulation period in the Chengkou area. The exploration results of the Y1 Well reveal good exploration prospects for shale gas in the lower Paleozoic strata in the Chengkou area.

Background: Remote ischemic postconditioning (RIPostC) appears to protect distant organs from ischemia-reperfusion injury (IRI). However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC. Methods: CNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated. Results: A total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks (RR = 0.37; 95% CI: 0.26–0.55; P < 0.00001). Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score (MD: 1.96; 95% CI: 2.18–1.75; P < 0.00001), modified Rankin Scale score (MD: 0.73; 95% CI: 1.20–0.25; P = 0.00300), and high-sensitivity C-reactive protein (MD: 4.17; 95% CI: 4.71–3.62; P < 0.00001) between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration. Conclusion: The present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI.

This article discusses the clinical outcomes of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) in patients with cirrhosis and esophageal varices. The study found that ESD was safe and effective in achieving complete resection of SEN in these patients, with high rates of successful removal. The results suggest that ESD may be a viable treatment option for this patient population. Another study discussed in the document found that ESD was feasible and safe in cirrhotic patients with SEN near esophageal varices, with high rates of successful removal and low rates of complications. The study suggests that ESD can be a potential treatment option for cirrhotic patients with SEN, even in the presence of esophageal varices. [Extracted from the article]

Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) and alcohol consumption have both increased in recent years, and there is debate as to whether nonheavy alcohol use is safe in MASLD. We analyzed the association between different nonheavy alcohol use patterns and at‐risk liver fibrosis among individuals with MASLD. Methods: We conducted a cross‐sectional study of 1072 eligible National Health and Nutrition Examination Survey participants with MASLD who reported nonheavy alcohol consumption. We used vibration‐controlled transient elastography to define the primary outcome of at‐risk liver fibrosis as >8.2 kPa (stage F2‐F4). Multivariable logistic regression models were used to determine the association of different alcohol consumption patterns (average drinks/day, drinking days/week, weekly alcohol intake, type of alcoholic beverage) and at‐risk hepatic fibrosis, controlling for demographic/socioeconomic, lifestyle/dietary, and metabolic risk factors. Results: Exclusive liquor or cocktail drinkers had a 5.02‐fold odds of at‐risk fibrosis (95% CI: 1.15–21.95) compared with non‐drinkers when controlling for potential confounders. While consuming an average of 2 drinks/day, ≥3 drinking days/week, or 1–3 drinks/week appeared to have a lower association with at‐risk fibrosis when controlling for demographic/socioeconomic risk factors, the association was not present after controlling for lifestyle/dietary and metabolic risk factors. Conclusions: There is an association between exclusive liquor/cocktail consumption and at‐risk liver fibrosis in patients with MASLD who report nonheavy alcohol consumption. In a nationally representative sample of US adults with metabolic dysfunction‐associated steatotic liver disease (MASLD), exclusive liquor or cocktail consumption is associated with a 5.02‐fold increased risk of liver fibrosis among nonheavy alcohol users. Nonheavy alcohol use overall was not associated with F2 or greater liver fibrosis after adjusting for confounders. Our findings highlight the need to investigate subcategories of drinking behavior that may lead to liver fibrosis even among those without heavy drinking. [ABSTRACT FROM AUTHOR]

A novel one-dimensional erbium complex [ErL2(NO3)(H2O)2]n (HL = 2-picolinic acid) was synthesized by hydrothermal methods, and its crystal structure was determined by single crystal x-ray diffraction. The complex crystallize in monoclinic system, space group C2/c with a = 15.7525(5) Å, b = 11.4958(4) Å, c = 9.7977(3) Å, β = 102.862(3) °, V = 1729.72(10) Å 3, C12H10ErN309, Mr = 507.49, Z = 4, Dc = 1.949 g⋅cm-3, F(000) = 972, μ = 4.901 mm-1, S = 1.119, λ(MoKα) = 0.071073 nm, R = 0.0239 and wR = 0.0668. The 2-picolinic acid ligand adopts bidentate bridging coordination mode to connect adjacent erbium ions to form a one-dimensional chain structure. A series of properties of the complex were measured by solid-state photoluminescence, solid-state diffuse reflection and differential scanning calorimetry. [ABSTRACT FROM AUTHOR]

Abstract Background microRNAs (miRNAs) are important regulators in plant growth and development. miR159 is a conserved miRNA among different plant species and has various functions in plants. Studies on miR159 are mostly done on model plant, Arabidopsis thaliana. In rice, studies on miR159 were either based upon genome-wide expression analyses focused upon responses to different nitrogen forms and abiotic stress or upon phenotypic studies of transgenic plants overexpressing its precursor. STTM (Short Tandem Target Mimic) is an effective tool to block the activity of endogenous mature miRNA activity in plant. Therefore, specific roles of miR159 in rice could be explored by down regulating miR159 through STTM. Results In this study, expression of mature miR159 was successfully suppressed by STTM which resulted in the increased expressions of its two targets genes, OsGAMYB and OsGAMYBL1 (GAMYB-LIKE 1). Overall, STTM159 plants exhibited short stature along with smaller organ size and reduction in stem diameter, length of flag leaf, main panicle, spikelet hulls and grain size. Histological analysis of stem, leaf and mature spikelet hull showed the reduced number of small vascular bundles (SVB), less number of small veins (SV) between two big veins (LV) and less cell number in outer parenchyma. Gene Ontology (GO) enrichment analysis of differentially expressed genes between wild type plants and STTM159 transgenic plants showed that genes involved in cell division, auxin, cytokinin (CK) and brassinosteroids (BRs) biosynthesis and signaling are significantly down-regulated in STTM159 plants. Conclusion Our data suggests that in rice, miR159 positively regulates organ size, including stem, leaf, and grain size due to the promotion of cell division. Further analysis from the RNA-seq data showed that the decreased cell divisions in STTM159 transgenic plants may result, at least partly from the lower expression of the genes involved in cell cycle and hormone homeostasis, which provides new insights of rice miR159-specific functions.

Abstract Background The APOL1 gene variants has been shown to be associated with an increased risk of multiple kinds of diseases, particularly in African Americans, but not in Caucasians and Asians. In this study, we explored the single nucleotide polymorphism (SNP) and haplotype diversity of APOL1 gene in different races provided by 1000 Genomes project. Methods Variants of APOL1 gene in 1000 Genome Project were obtained and SNPs located in the regulatory region or coding region were selected for genetic variation analysis. Total 2504 individuals from 26 populations were classified as four groups that included Africa, Europe, Asia and Admixed populations. Tag SNPs were selected to evaluate the haplotype diversities in the four populations by HaploStats software. Results APOL1 gene was surrounded by some of the most polymorphic genes in the human genome, variation of APOL1 gene was common, with up to 613 SNP (1000 Genome Project reported) and 99 of them (16.2%) with MAF ≥ 1%. There were 79 SNPs in the URR and 92 SNPs in 3’UTR. Total 12 SNPs in URR and 24 SNPs in 3’UTR were considered as common variants with MAF ≥ 1%. It is worth noting that URR-1 was presents lower frequencies in European populations, while other three haplotypes taken an opposite pattern; 3’UTR presents several high-frequency variation sites in a short segment, and the differences of its haplotypes among different population were significant (P

Abstract The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. In this study, poly(L-γ-glutamyl-glutamine)-paclitaxel (PGG-PTX), as a model polymer, was chemically conjugated with Gd-DTPA (Gd-diethylenetriaminepentaacetic acid), a T1-contrast agent of MRI, to prepare a Gd-DTPA-conjugated PGG-PTX (PGG-PTX-DTPA-Gd) delivery system used for tumor theranostics. PGG-PTX-DTPA-Gd can be self-assembled to NPs in water with a z-average hydrodynamic diameter about 35.9 nm. The 3 T MRI results confirmed that the relaxivity of PGG-PTX-DTPA-Gd NPs (r1 = 18.98 mM−1S−1) was increased nearly 4.9 times compared with that of free Gd-DTPA (r1 = 3.87 mM−1S−1). The in vivo fluorescence imaging results showed that PGG-PTX-DTPA-Gd NPs could be accumulated in the tumor tissue of NCI-H460 lung cancer animal model by EPR effect, which was similar to PGG-PTX NPs. The MRI results showed that compared with free Gd-DTPA, PGG-PTX-DTPA-Gd NPs showed significantly enhanced and prolonged signal intensity in tumor tissue, which should be attributed to the increased relaxivity and tumor accumulation. PGG-PTX-DTPA-Gd NPs also showed effective antitumor effect in vivo. These results indicated that PGG-PTX-DTPA-Gd NPs are an effective delivery system for tumor theranostics, and should have a potential value in personalized treatment of tumor.

We carried out a pool culture experiment to determine the optimal water treatment depth in loam and clay soils during the late growth stage of super rice. Three controlled water depth treatments of 0–5, 0–10 and 0–15 cm below the soil surface were established using alternate wetting and drying irrigation, and the soil water potential (0 to –25 kPa) was measured at 5, 10 and 15 cm. A 2-cm water layer was used as the control. We measured soil enzyme activities, root antioxidant enzyme activities, chlorophyll fluorescence parameters, and rice yield. The results showed that the 0–5-cm water depth treatment significantly increased root antioxidant enzyme activities in loam soil compared with the control, whereas soil enzyme activities, chlorophyll fluorescence parameters and yield did not differ from those of the control. The 0–10- and 0–15-cm water depth treatments also increased root antioxidant enzyme activities, whereas soil enzyme activities, chlorophyll fluorescence parameters and yield decreased. In clay soil, the soil enzyme activities, root antioxidant enzyme activities, chlorophyll fluorescence parameters, and yield did not change with the 0–5-cm water treatment, whereas the 0–10- and 0–15-cm water treatments improved these parameters. Therefore, the appropriate depths for soil water during the late growth period of rice with a 0 to –25 kPa water potential were 5 cm in loam and 15 cm in clay soil.

Background: Cadmium (Cd), a common environmental heavy metal and endocrine disruptor, is known to exert toxic effects on the testes. However, the mechanisms accounting for its toxicity in mature spermatozoa remain unclear. Methods: Adult male C57BL/6 mice were orally administered with CdCl2 for 5 weeks at 3 mg·kg-1·day-1. Additionally, mouse spermatozoa were incubated in vitro with different doses of CdCl2 (0, 10, 50, 250 µM). Several sperm functions including the sperm motility, viability and acrosome reaction (AR) ratio were then examined. Furthermore, the current and expression levels of both the sperm-specific Ca2+ channel (CatSper) and the sperm-specific K+ channel (KSper) were evaluated by patch-clamping and western blotting, respectively. Results: Our data showed that the motility, viability and AR of sperm exposed to cadmium significantly decreased in vivo and in vitro. Interestingly, these changes were correlated with changes in CatSper but not KSper. Conclusion: The findings indicate sperm dysfunction during both chronic and acute cadmium exposure as well as a specific role for CatSper in the reproductive toxicity of cadmium.

Nitrogen is one of the most important nutrient indicators for the growth of crops, and is closely related to the chlorophyll content of leaves and thus influences the photosynthetic ability of the crops. In this study, five hybrid rice varieties were cultivated during one entire growing period in one experimental field supplied with six nitrogen fertilizer levels. Visible and near infrared (vis/NIR) reflectance spectroscopy combined with multivariate analysis was used to identify hybrid rice varieties and nitrogen fertilizer levels, as well as to detect chlorophyll content associated with nitrogen levels. The support vector machine (SVM) algorithm was applied to identify five varieties of hybrid rice and six levels of nitrogen fertilizer. The results demonstrated that different varieties of hybrid rice for each nitrogen level can be well distinguished except for the highest nitrogen level, and no nitrogen level for each rice variety can be completely identified from the other five nitrogen levels. Further, 12 spectral indices combined with partial least square (PLS) analysis were applied for estimating chlorophyll content of rice leaves from plants subjected to different nitrogen levels, and a root mean square error of cross-validation (RMSECV) of 0.506, a coefficient of determination (R2) of 97.8% and a ratio of performance to deviation (RPD) of 4.6 for all rice varieties indicated this as a preferable procedure. This study demonstrates that Vis/NIR spectroscopy can have a great potential for identification of rice varieties and evaluation of nitrogen fertilizer levels.

BACKGROUND:The treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients in the 1990s in Taiwan was not satisfactory. To strengthen programmatic management of drug-resistant tuberculosis (PMDT), Taiwan MDR-TB Consortium (TMTC) was established in 2007. We assess the performance and epidemiologic impact of TMTC. METHODOLOGY/PRINCIPLE FINDINGS:We analyzed the trends of proportion of TB cases with drug susceptibility testing, enrollment of MDR-TB patients into TMTC and outcomes of treatment of all MDR-TB patients in Taiwan from 2007-2016. We computed the trends of both incidence and prevalence of MDR-TB from 2007-2016. We assessed the trends of MDR-TB among both new and recurrent TB cases. The proportion of TB cases with drug susceptibility testing results increased from 24.2% in 2007 to 97.9% in 2016. Of the 1,452 MDR-TB patients who were eligible for TMTC care, 1,197 (82.4%) were enrolled in TMTC, in whom 82.9% had treatment success. MDR-TB incidence was 9.0 cases per million in 2007, which declined to 4.6 cases per million in 2016 (p