Differential Expression of KIF18B in Gastric Cancer and Its Role in Chemotherapy Sensitivity.

Gastric cancer (GC) is a main cause of cancer death in the world, and improving the chemotherapy sensitivity can enhance the chemotherapy efficacy of GC. The study objective is to explore the differential KIF18B expression in GC and its effect on GC chemotherapy sensitivity. The KIF18B expression in GC tissues and adjacent normal tissues was analyzed by real-time quantitative polymerase chain reaction. The relationship between differential KIF18B expression and different clinicopathological features was detected. It was found that KIF18B was highly expressed in GC tissues, and KIF18B expression was differential in patients with different clinicopathological features. The upregulation of KIF18B has a positive correlation with the poor therapeutic effect and high KIF18 was associated with lower 3-year overall survival and disease-free survival. The KIF18B-downregulated NCI-N87 cells were constructed and tested by cell counting kit-8 assay and colony formation. Cell migration and invasion were detected by Transwell assay. The xenograft tumor model was established to observe the effect of KIF18B on the efficacy of chemotherapy. The upregulation of KIF18B reduced the chemotherapy sensitivity of GC cells and enhanced their proliferation, migration, and invasion. Silencing KIF18B inhibited tumor growth and promoted chemotherapy efficacy in vivo. In summary, KIF18B inhibitor may have a potential function for improving the efficacy of chemotherapy in GC.

TIM22 and TIM29 inhibit HBV replication by up-regulating SRSF1 expression.

Hepatitis B virus (HBV) infection is a serious global health problem. After the viruses infect the human body, the host can respond to the virus infection by coordinating various cellular responses, in which mitochondria play an important role. Evidence has shown that mitochondrial proteins are involved in host antiviral responses. In this study, we found that the overexpression of TIM22 and TIM29, the members of the inner membrane translocase TIM22 complex, significantly reduced the level of intracellular HBV DNA and RNA and secreted HBV surface antigens and E antigen. The effects of TIM22 and TIM29 on HBV replication and transcription is attributed to the reduction of core promoter activity mediated by the increased expression of SRSF1 which acts as a suppressor of HBV replication. This study provides new evidence for the critical role of mitochondria in the resistance of HBV infection and new targets for the development of treatment against HBV infection.

Comparative study of female pelvic floor among undeformed high-resolution thin-sectional anatomical (visible human) images and MRI and ultrasound images.

PURPOSE: Using visible human, MRI and ultrasound images, we aim to provide an anatomical basis for the identification and diagnosis of pelvic floor structure and disease by ultrasound imaging. METHODS: One Chinese visible human (CVH) image, one American visible human image, 9 MRI images of normal volunteers, and 40 ultrasound images of normal volunteers or pelvic organ prolapse patients were used. Pelvic organs, pelvic floor muscles, and the connective tissue in CVH, VHP, MRI, and ultrasound images were selected for comparative study. RESULTS: We successfully identified the boundary of the anal sphincter complex, including the subcutaneous, superficial, and deep parts of the external anal sphincter, conjoined longitudinal muscles and internal anal sphincter; the levator ani muscle (LAM), including the internal and external parts of the pubovisceral muscle and the superficial and deep parts of the puborectal muscle; the urethral sphincter complex, including the urethral sphincter proper and the urethral compressor; and the perineal body, the rectoperineal muscle and superficial transverse perineal muscle. CONCLUSIONS: We successfully recognized and studied the location, subdivisions, 2D morphology and spatial relationships of the LAM, anal sphincter complex, urethral sphincter complex and perineal body in ultrasound images, thereby helping sonologists or clinicians accurately identify pelvic floor muscles and supporting structures in ultrasound images.

The role of iTr35 cells in the inflammatory response and fibrosis progression of systemic sclerosis.

OBJECTIVE: To evaluate the role of induced immunosuppressive T regulatory (iTr) 35 cells in SSc-related inflammation and fibrosis. METHODS: Sixty-eight SSc patients were enrolled in this study. Subsets of iTr35 and Tr1 were measured by flow cytometry. IL-35 and IL-10 levels were measured using ELISA. Expressions of iTr35, Tr1, fibrosis-related genes and proteins associated with signalling pathways were determined using immunofluorescence, western blot and immunohistochemistry assays. RESULTS: In peripheral blood, the proportions of the iTr35 cells were higher and Tr1 cells were lower than the control group. Similarly, IL-35 expression was increased, while IL-10 levels were decreased. In fibroblasts from skin tissue, the expression levels of EBI3, IL-12Ap35, Foxp3 and IL-10 were decreased, but collagen I, TGF-ß, alpha smooth muscle actin (α-SMA) and fibronectin levels were increased. Phosphorylated STAT3/6 were increased, but iTr35 and Tr1 cell levels were significantly decreased. When CD4+ cells were incubated with both recombinant human (rh)IL-35 and rhIL-10, the cell numbers of iTr35 and Tr1 were greater than the same type of cells treated with rhIL-35 or rhIL-10 alone. However, the viability of conventional CD4+ T cells was decreased by gradually increasing iTr35 cells. Moreover, iTr35 cells affected α-SMA expression through the STAT3/6 signalling pathway. CONCLUSION: Both iTr35 and Tr1 cells are involved in SSc-related inflammation and fibrosis. IL-35 can induce iTr35 cells, showing a synergistic effect with IL-10. We also found that iTr35 cells can inhibit T cell proliferation and differentiation via the STAT3/6 signalling pathway, thereby causing fibrosis.

Exosomes from adipose-derived mesenchymal stem cells improve liver fibrosis by regulating the miR-20a-5p/TGFBR2 axis to affect the p38 MAPK/NF-κB pathway.

OBJECTIVE: Human adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) are active constituents for treating liver fibrosis. This paper attempted to preliminarily explain the functional mechanism of ADSC-Exos in liver fibrosis through the p38 MAPK/NF-κB pathway. METHODS: The cell models of hepatic fibrosis were established by inducing LX-2 cells with TGF-ß1. Mouse models of liver fibrosis were established by treating mice with CCl4. The in vivo and in vitro models of liver fibrosis were treated with ADSC-Exos. ADSCs were identified by flow cytometry/Alizarin red/oil red O/alcian blue staining. ADSC-Exos were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. LX-2 cell proliferation/viability were evaluated by MTT/BrdU assays. Exosomes were tracked in vivo and body weight changes in mice were monitored. Hepatic pathological changes were observed by HE/Masson staining. α-SMA/collagen I levels in liver tissues were assessed by immunohistochemistry. HA/PIIINP concentrations were measured using the magnetic particle chemiluminescence method. Liver function was assessed using an automatic analyzer. miR-20a-5p level was measured by RT-qPCR. The mRNA levels of fibrosis markers were determined by RT-qPCR, and their protein levels and levels of MAPK/NF-κB pathway-related proteins, as well as TGFBR2 protein level were measured by Western blot. The P65 nuclear expression in mouse liver tissues was quantified by immunofluorescence. RESULTS: ADSC-Exos suppressed TGF-ß1-induced LX-2 cell proliferation and fibrosis and reduced mRNA and protein levels of fibrosis markers in vitro. ADSC-Exos ameliorated liver fibrosis by inhibiting the p38 MAPK/NF-κB pathway activation. ADSC-Exos inhibited activation of the p38 MAPK/NF-κB pathway via regulating the miR-20a-5p/TGFBR2 axis. The in vivo experiment asserted that ADSC-Exos were mainly distributed in the liver, and ADSC-Exos relieved liver fibrosis in mice, which was evidenced by alleviating decreased body weight, reducing collagen and enhancing liver function, and repressed the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis. CONCLUSION: ADSC-Exos attenuated liver fibrosis by suppressing the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis.

Effects of secondary release of chromium and vanadium on soil properties, nutrient cycling and bacterial communities in contaminated acidic paddy soil.

Although the contamination situation of chromium (Cr) and vanadium (V) have been revealed, the effects of their re-release on ecological risk in contaminated acidic paddy soil are unclear. To evaluate the effects, we assigned soil microcosms across three different concentration (100, 200, 300 mg/L) and introduced Cr and V alone or combination into an already slightly contaminated acidic soil. We found that Cr and V alone or interacted to increased soil bioavailable-metals, changed soil properties and nutrients to varying degrees. Meanwhile, soil ammoniacal nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) contents, nitrogen (N) -cycling enzyme activities, microbial mass N were significantly influenced by Cr addition. Which demonstrated that Cr re-release may disturb soil N cycle. However, V alone significantly improved soil NO3--N contents, cellulase and dehydrogenase activities, soil respiration intensity and microbial mass carbon: nitrogen. Meanwhile, V addition also decreased bacterial diversity while Cr addition increased bacterial diversity and shaped new bacterial community, some V(V) and Cr (VI) reducing bacteria were identified. Heatmap of Pearson correlation and Redundancy analysis showed that NH4+-N, NO3--N, Potassium, Phosphorus, and Cr played an important role in bacterial community structure. These findings suggested that re-release of Cr and V disturbed soil function and raised ecological risks, and the power to destroy the ecosystem stability originated from Cr was much stronger than V. This study was contributed to understand the effects of Cr and V re-release on microecology in contaminated acidic agricultural soil.

Altered CD4+ T cell and cytokine levels in peripheral blood and skin samples from systemic sclerosis patients and IL-35 in CD4+ T cell growth.

OBJECTIVE: This study explored the role of IL-35 in CD4+ T lymphocyte and human skin fibroblast (HSF) activity and cytokine levels in systemic sclerosis. METHODS: Blood and skin biopsies were collected from 41 patients and 39 healthy controls to assess CD4+ T lymphocytes and IL-35-related factors. CD4+ T lymphocytes were co-cultured with HSFs, recombinant human IL-35 and IL-35 mAb to evaluate the cell viability, activation of CD4+ T lymphocytes and HSF cells. RESULTS: The proportion of blood Th1/Th2 was lower and Th17/Treg was higher in patients than in controls (P < 0.05). IL-35 and IL-17A levels were higher and IFN-γ, IL-10 and TGF-ß levels were lower in patients than in controls. IL-17A, forkhead box P3, TGF-ß1 and collagen type I (COL-1) mRNA and phospho (p)-signal transducer and activator of transcription (STAT) 1 and p-STAT4 were higher in skin tissues from patients than in those from controls (P < 0.05). IL-6 levels were higher, whereas IL-10 levels were lower in cell culture supernatants. α-Smooth muscle actin (α-SMA) and COL-1 proteins and Ki67 positivity were higher in CD4+ T + HSF cells from patients than in those from controls. Recombinant human IL-35 treatment inhibited proliferation (P < 0.001), but increased IL-10 and decreased IL-17A, α-SMA and COL-1 secretion into the conditioned medium of CD4+ T lymphocytes + HSFs from patients compared with those from controls. IL-35 mAb blocked the effects of IL-35 in CD4+ T + HSF cells (P < 0.05). CONCLUSIONS: IL-35 plays an inhibitory role in CD4+ T lymphocyte proliferation but induces Treg cell differentiation by STAT1 signalling activation, HSF proliferation and collagen expression in systemic sclerosis.

Electrochemically functionalized graphene for highly sensitive detection of nitrofurazone.

Graphene nanosheets (GS) were prepared by ultrasonic exfoliation of bulk graphite in N-methyl-2-pyrrolidone with the assistance of sodium pyrophosphate. The obtained GS suspension was modified on a glassy carbon electrode (GS/GCE), and then functionalized at different voltages (e.g. 1.0, 1.4 and 1.6 V) for 2 min in pH 7.0 phosphate buffer. The electrochemically functionalized GS/GCE (i.e. EGS/GCE) possesses more oxygen-containing groups and a higher defect level. More importantly, the active response area, electron transfer ability and interface adsorption capacity of the EGS/GCE enhanced remarkably. The possible mechanism of the performance enhancement is discussed, and the sensing application of the EGS/GCE in the detection of nitrofurazone (NFZ) is investigated. Compared with the GS/GCE, the EGS/GCE is much more active for NFZ oxidation and greatly increases the detection sensitivity. As a result, a highly sensitive electrochemical detection method has been developed for NFZ, with a detection limit of 2.1 nM. The practical application of the EGS/GCE was tested in fish meat samples, showing good accuracy and feasibility.

Cepharanthine sensitizes human triple negative breast cancer cells to chemotherapeutic agent epirubicin via inducing cofilin oxidation-mediated mitochondrial fission and apoptosis.

Inhibition of autophagy has been accepted as a promising therapeutic strategy in cancer, but its clinical application is hindered by lack of effective and specific autophagy inhibitors. We previously identified cepharanthine (CEP) as a novel autophagy inhibitor, which inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. In this study we investigated whether and how inhibition of autophagy/mitophagy by cepharanthine affected the efficacy of chemotherapeutic agent epirubicin in triple negative breast cancer (TNBC) cells in vitro and in vivo. In human breast cancer MDA-MB-231 and BT549 cells, application of CEP (2 µM) greatly enhanced cepharanthine-induced inhibition on cell viability and colony formation. CEP interacted with epirubicin synergistically to induce apoptosis in TNBC cells via the mitochondrial pathway. We demonstrated that co-administration of CEP and epirubicin induced mitochondrial fission in MDA-MB-231 cells, and the production of mitochondrial superoxide was correlated with mitochondrial fission and apoptosis induced by the combination. Moreover, we revealed that co-administration of CEP and epirubicin markedly increased the generation of mitochondrial superoxide, resulting in oxidation of the actin-remodeling protein cofilin, which promoted formation of an intramolecular disulfide bridge between Cys39 and Cys80 as well as Ser3 dephosphorylation, leading to mitochondria translocation of cofilin, thus causing mitochondrial fission and apoptosis. Finally, in mice bearing MDA-MB-231 cell xenografts, co-administration of CEP (12 mg/kg, ip, once every other day for 36 days) greatly enhanced the therapeutic efficacy of epirubicin (2 mg/kg) as compared with administration of either drug alone. Taken together, our results implicate that a combination of cepharanthine with chemotherapeutic agents could represent a novel therapeutic strategy for the treatment of breast cancer.

Transthoracic, thoracoabdominal, and transabdominal surgical approaches for gastric cardia adenocarcinomas: a survival evaluation based on a cohort of 7103 patients.

BACKGROUND: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. METHODS: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan-Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. RESULTS: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages. CONCLUSION: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Hypothesis generation: Quantitative research to levator ani muscle injury based on MRI texture analysis.

AIM: Patients with pelvic organ prolapse (POP) mostly have injury to the levator ani muscle (LAM). We aimed to assess LAM injury in POP patients by quantifying texture feature (TF) ratios between the LAM and the obturator internus muscle (OIM) using texture analysis. METHODS: This study retrospectively enrolled 32 participants, including 24 patients with POP and eight people with normal pelvic floor muscles. TFs of the LAM and the OIM were extracted using LIFEx version 6.30, and an independent samples t-test was performed to determine TF ratios characterizing LAM injury. After dimension reduction and binary logic analysis, the optimal TF ratio was obtained and the LAM injury quantitative evaluation was proposed. Spearman's correlation was performed to explore the correlations between TF ratios and clinical characteristics. We compared the diagnostic performance of quantitative evaluation and visual evaluation. RESULTS: There were significant differences in 13 TF ratios between the POP and control groups. The area under the receiver operating characteristic curve of the integrated TF ratio was 0.948. Integrated TF ratio was significantly correlated with body mass index, pregnancies, and vaginal deliveries but had no correlation with LAM volume, hiatal area or abortions. Compared with the visual evaluation, the diagnostic accuracy of the quantitative evaluation had improved by 63.2% and 14.3% in the "minor defect" and "major defect" categories, respectively. CONCLUSION: The integrated TF ratio can be used as a new quantifiable index to characterize LAM injury. The TF evaluation provides a potential role in LAM injury noninvasive diagnostic.

HIF-1α Causes LCMT1/PP2A Deficiency and Mediates Tau Hyperphosphorylation and Cognitive Dysfunction during Chronic Hypoxia.

Chronic hypoxia is a risk factor for Alzheimer's disease (AD), and the neurofibrillary tangle (NFT) formed by hyperphosphorylated tau is one of the two major pathological changes in AD. However, the effect of chronic hypoxia on tau phosphorylation and its mechanism remains unclear. In this study, we investigated the role of HIF-1α (the functional subunit of hypoxia-inducible factor 1) in tau pathology. It was found that in Sprague-Dawley (SD) rats, global hypoxia (10% O2, 6 h per day) for one month induced cognitive impairments. Meanwhile it induced HIF-1α increase, tau hyperphosphorylation, and protein phosphatase 2A (PP2A) deficiency with leucine carboxyl methyltransferase 1(LCMT1, increasing PP2A activity) decrease in the rats' hippocampus. The results were replicated by hypoxic treatment in primary hippocampal neurons and C6/tau cells (rat C6 glioma cells stably expressing human full-length tau441). Conversely, HIF-1α silencing impeded the changes induced by hypoxia, both in primary neurons and SD rats. The result of dual luciferase assay proved that HIF-1α acted as a transcription factor of LCMT1. Unexpectedly, HIF-1α decreased the protein level of LCMT1. Further study uncovered that both overexpression of HIF-1α and hypoxia treatment resulted in a sizable degradation of LCMT1 via the autophagy--lysosomal pathway. Together, our data strongly indicated that chronic hypoxia upregulates HIF-1α, which obviously accelerated LCMT1 degradation, thus counteracting its transcriptional expression. The increase in HIF-1α decreases PP2A activity, finally resulting in tau hyperphosphorylation and cognitive dysfunction. Lowering HIF-1α in chronic hypoxia conditions may be useful in AD prevention.

Effect of slow-released biomass alkaline amendments oyster shell on microecology in acidic heavy metal contaminated paddy soils.

Soil ecosystem functions and microbial community structure were severely impaired with long-term cadmium (Cd) contamination and acidification. To investigate the effect of amendments on soil physiochemical parameters and soil micro-ecology in acidic Cd contaminated soil, this study was conducted in a pot experiment with the application of calcium amendments, oyster shell powders (OS) and limestone (LM). Each amendment applied at ratios of 1.0%, 3.0%, and 5.0% (w/w), respectively. The results showed that the application of amendments increased the soil pH by 2.10-2.88, the bioavailable Cd decreased by 12.49%-19.48%, and un-bioavailable Cd increased by 96.57%-200.7%. The OS increased the richness index (Chao and Ace increased by 13.23%-16.20% and 7.13%-47.63%), and LM increased the microbial diversity index (Shannon increased by 1.14%-8.72% and Simpson indexes decreased by 28.00%-63.61%). In LM groups, soil microbial communities were significantly altered with increasing application concentrations, the relative abundance of phylum Proteobacteria, Bacteroidota and Gemmatimonadota increased, while Firmicute, Actinobacteria, Chloroflexi decreased. In OS treatments, the soil microbial community structure was basically unchanged. The correlation analysis showed that pH, TN, TP, CEC, OM were the dominant factors affecting the microbial community. This study has shown that application of amendments could effectively reduce the Cd bioavailability in soil, but LM altered the soil microbial community structure, while OS maintained the soil microbiological structure.

Simultaneous detection of 4-chlorophenol and 4-nitrophenol using a Ti3C2Tx MXene based electrochemical sensor.

Developing a sensitive and rapid detection method for 4-chlorophenol (4-CP) and 4-nitrophenol (4-NP) is very important due to their high toxicity. In this work, bulk Ti3AlC2 powder was etched to Ti3C2Tx for the first time through a hydrothermal reaction in NaF/HCl solution. After ultrasonication in N-methylpyrrolidone (NMP), Ti3C2Tx powder was successfully exfoliated into multilayered Ti3C2Tx nanosheets (i.e. Ti3C2Tx MXene). The prepared Ti3C2Tx MXene not only has a large electrochemical surface area for the oxidation of 4-CP and 4-NP, but also lowers their electron transfer resistance. As a result, the oxidation signals of 4-CP and 4-NP are significantly improved on the surface of the Ti3C2Tx MXene. Based on the remarkable signal amplification of the Ti3C2Tx MXene, a sensitive and rapid method was developed for the simultaneous detection of 4-CP and 4-NP. The linear range is from 0.1 to 20.0 µM for 4-CP, and from 0.5 to 25.0 µM for 4-NP, with detection limits of 0.062 µM (4-CP) and 0.11 µM (4-NP). This method was used in wastewater samples, and the accuracy was confirmed to be good by high-performance liquid chromatography.

First Report of Athelia rolfsii Causing Southern Blight on Sarcandra glabra in China.

Sarcandra glabra, belonging to the family Chloranthaceae, is a Chinese medicinal plant. The whole dry plant can be used as a medicine; it is rich in bioactive phytochemicals that possess anti-bacterial, anti-inflammatory, anti-oxidant, and anti-tumor properties (Xie et al. 2020). The current market price of S. glabra is around US$5/kg, and the annual demand is 3 500 000~4 000 000 kg in China (Pan et al. 2007). To meet consumer demand for safe and high-quality herbal products, the artificial cultivation of S. glabra has been vigorously promoted. In 2020, it was observed that a plant disease affected S. glabra growth in Hunan province. The disease symptoms included constriction at the base of the stem, with decay and a white mycelium covering. The plants finally died with a disease incidence ranging from 15% to 20%. Using our previously published methods (Yi et al. 2019), one fungal isolate was isolated from the cultured symptomatic stem tissue on potato dextrose agar (PDA) medium and was named as Kb. The isolate was subsequently transferred into 70% glycerol for preservation. The Kb colony varied in color from white to light yellow. The septate hyphae grew rapidly on PDA medium, at approximately 25 mm/day, at 28 °C. On the fifth day, rhizomorphs were formed at the edge and on the center of the PDA plate. On the sixth day, sclerotia developed into a rapeseed shape (d = 1.2~2.3 mm) with a smooth surface, and with white, yellow, or chestnut brown coloring. Morphologically, Kb was similar to Sclerotium rolfsii (Sun et al. 2020). Vigorously growing aerial hyphae were selected for molecular identification. The internal transcribed spacers (ITS) were amplified using the primer pairs ITS1/ITS4 (Glass et al. 1995). BLAST searches against Genbank indicated that Kb's ITS sequence shared 97% similarity with that of Athelia rolfsii (MN696630.1). Based on morphological and molecular characteristics, Kb was identified as A. rolfsii. The sequence was deposited in GenBank (MW288292). Pathogenicity tests were carried out using the following procedures. Three healthy S. glabra seedlings were inoculated at the stem base with a PDA plug (5 mm in diameter) covered with 5-day-old fungal mycelium cultured at 28 °C, while the remaining three seedlings were inoculated with distilled water only, as the control. Plants were incubated in a greenhouse at 28 °C. At 7 days post inoculation, the inoculated sites infected with the putative pathogen displayed identical constrictions as previously observed in the field. In contrast, the controls remained symptomless. The pathogen was reisolated from these infected seedlings, and its culture showed the same morphological and molecular traits as the original isolates. No pathogens were isolated from the control plants. Pathogenicity tests were repeated three times. Koch's postulates were fulfilled. Although S. rolfsii has been previously reported to cause Southern Blight on mung bean crops in China (Sun et al. 2020), this is the first report on A. rolfsii causing similar symptoms of Southern Blight on S. glabra in Hunan Province, China. Identification of the pathogens causing each disease is important for the development of effective disease management strategies and for extensive artificial cultivation.

Dark response genes: a group of endogenous pendulum/timing players in maize?

MAIN CONCLUSION: Maize has a set of dark response genes, expression of which is influenced by multiple factor and varies with maize inbred lines but without germplasm specificity. The response to photoperiod is a common biological issue across the species kingdoms. Dark is as important as light in photoperiod. However, further in-depth understanding of responses of maize (Zea mays) to light and dark transition under photoperiod is hindered due to the lack of understanding of dark response genes. With multiple public "-omic" datasets of temperate and tropical/subtropical maize, 16 maize dark response genes, ZmDRGs, were found and had rhythmic expression under dark and light-dark cycle. ZmDRGs 6-8 were tandemly duplicated. ZmDRGs 2, 13, and 14 had a chromosomal collinearity with other maize genes. ZmDRGs 1-11 and 13-16 had copy-number variations. ZmDRGs 2, 9, and 16 showed 5'-end sequence deletion mutations. Some ZmDRGs had chromatin interactions and underwent DNA methylation and/or m6A mRNA methylation. Chromosomal histones associated with 15 ZmDRGs were methylated and acetylated. ZmDRGs 1, 2, 4, 9, and 13 involved photoperiodic phenotypes. ZmDRG16 was within flowering-related QTLs. ZmDRGs 1, 3, and 6-11 were present in cis-acting expression QTLs (eQTLs). ZmDRGs 1, 4, 6-9, 11, 12, and 14-16 showed co-expression with other maize genes. Some of ZmDRG-encoded ZmDRGs showed obvious differences in abundance and phosphorylation. CONCLUSION: Sixteen ZmDRGs 1-16 are associated with the dark response of maize. In the process of post-domestication and/or breeding, the ZmDRGs undergo the changes without germplasm specificity, including epigenetic modifications, gene copy numbers, chromatin interactions, and deletion mutations. In addition to effects by these factors, ZmDRG expression is influenced by promoter elements, cis-acting eQTLs, and co-expression networks.

Research progress on alternative non-classical mechanisms of PCSK9 in atherosclerosis in patients with and without diabetes.

The proprotein convertase subtilisin/kexin type 9 (PCSK9) acts via a canonical pathway to regulate circulating low-density lipoprotein-cholesterol (LDL-C) via degradation of the LDL receptor (LDLR) on the liver cell surface. Published research has shown that PCSK9 is involved in atherosclerosis via a variety of non-classical mechanisms that involve lysosomal, inflammatory, apoptotic, mitochondrial, and immune pathways. In this review paper, we summarized these additional mechanisms and described how anti-PCSK9 therapy exerts effects through these mechanisms. These additional pathways further illustrate the regulatory role of PCSK9 in atherosclerosis and offer an in-depth interpretation of how the PCSK9 inhibitor exerts effects on the treatment of atherosclerosis.

Spatio-temporal dynamics of EEG features during sleep in major depressive disorder after treatment with escitalopram: a pilot study.

BACKGROUND: Previous studies have shown escitalopram is related to sleep quality. However, effects of escitalopram on dynamics of electroencephalogram (EEG) features especially during different sleep stages have not been reported. This study may help to reveal pharmacological mechanism underlying escitalopram treatment. METHODS: The spatial and temporal responses of patients with major depressive disorder (MDD) to escitalopram treatment were analyzed in this study. Eleven MDD patients and eleven healthy control subjects who completed eight weeks' treatment of escitalopram were included in the final statistics. Six-channel sleep EEG signals were acquired during sleep. Power spectrum and nonlinear dynamics were used to analyze the spatio-temporal dynamics features of the sleep EEG after escitalopram treatment. RESULTS: For temporal dynamics: after treatment, there was a significant increase in the relative energy (RE) of Î´1 band (0.5 - 2 Hz), accompanied by a significant decrease in the RE of ß2 band (20 - 30 Hz). Lempel-Ziv complexity and Co - complexity values were significantly lower. EEG changes at different sleep stages also showed the same regulation as throughout the night sleep. For spatio dynamics: after treatment, the EEG response of the left and right hemisphere showed asymmetry. Regarding band-specific EEG complexity estimations, δ1 and ß2 in stage-1 and δ1 in stage-2 sleep stage in frontal cortex is found to be much more sensitive to escitalopram treatment in comparison to central and occipital cortices. CONCLUSIONS: The sleep quality of MDD patients improved, EEG response occurred asymmetry in left and right hemispheres due to escitalopram treatment, and frontal cortex is found to be much more sensitive to escitalopram treatment. These findings may contribute to a comprehensive understanding of the pharmacological mechanism of escitalopram in the treatment of depression.

[Distribution characteristics of Chinese medicine resources in Turpan Basin, Xinjiang].

Based on the results of the fourth national survey of traditional Chinese medicine resources in Turpan city, Xinjiang, this study counted the types of traditional Chinese medicine resources in Turpan Basin. The spatial distribution differences of traditional Chinese medicine resources in Turpan Basin of Xinjiang were analyzed by using grid technology, trend surface analysis, global spatial autocorrelation analysis, and local spatial autocorrelation analysis, so as to clarify the overall change trend and aggregation degree of traditional Chinese medicine resources in Turpan Basin in horizontal and vertical directions. The results showed the following: in the horizontal direction, the species richness of traditional Chinese medicine resources in the central part of Turpan Basin was high, and there were great differences in the species richness of traditional Chinese medicine resources in Turpan Basin under different grid sizes. The spatial scale effect of the richness of traditional Chinese medicine resources in Turpan Basin is obvious. Among them, under the 30 km×30 km scale, the richness of the types of Chinese medicine resources shows a high spatial correlation, and the richness of the types of Chinese medicine resources at 5 km×5 km scale presents a near random distribution state, and the richness of the types of Chinese medicine resources at 80, 90, and 100 km scale sits negatively related. Vertical direction, Chinese medicine resources appear rich at the range of-154-150 m and 900-1 050 m following by range of 1 050-1 200 m.

Desmin deficiency is not sufficient to prevent corneal fibrosis.

The type III intermediate filament (IF) proteins vimentin and desmin are sequentially overexpressed in stromal myofibroblasts over the period when fibrosis sets in after corneal injury. Prior findings have revealed vimentin-deficient mice are significantly protected from corneal fibrosis after alkali injury, which has implicated this IF protein as an important regulator of corneal fibrosis. It has remained as yet unproven whether desmin contributes in any significant manner to corneal fibrosis. Here we have employed desmin-deficient (Des KO) mice in the corneal alkali injury model and show that injured Des KO mice develop fibrosis and show similar levels of corneal opacity at 14 days post-injury as wild type (WT) mice and retain this phenotype even at 30d post injury. Des KO corneas from injured mice show upregulation of vimentin and alpha-smooth muscle actin expression to equivalent levels as WT corneas, illuminating that desmin deficiency does not interfere with myofibrobast differentiation. Employing the small molecule withaferin A (WFA), an inhibitor of vimentin, we show that WFA treatment causes the decrease in steady state levels of vimentin and serine 38 phosphorylated vimentin, the latter a biomarker associated with corneal fibrosis, and improved corneal clarity through blockade of myofibroblast differentiation. To investigate further the mechanism of fibrosis in desmin deficiency, we examined keratin 8 expression in the epithelium, and found reduced levels of this cytokeratin in injured Des KO corneas compared to WT corneas. This finding also corroborates the decrease of cell proliferation in injured Des KO corneas compared to that in WT corneas. The fibrotic phenotype of Des KO corneas also features abundant vascularization, further exemplifying the magnitude of corneal pathology. Together, these findings illuminate that desmin does not contribute significantly to corneal fibrosis in this injury model.