Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

Machine Learning Analysis Classifies Patients with Primary Angle-Closure Glaucoma Using Abnormal Brain White Matter Function.

Objective: Primary angle-closure glaucoma (PACG) is a globally prevalent, irreversible eye disease leading to blindness. Previous neuroimaging studies demonstrated that PACG patients were associated with gray matter function changes. However, whether the white matter(WM) function changes in PACG patients remains unknown. The purpose of the study is to investigate WM function changes in the PACG patients. Methods: In total, 40 PACG patients and 40 well-matched HCs participated in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We compared between-group differences between PACG patients and HC in the WM function using amplitude of low-frequency fluctuations (ALFF). In addition, the SVM method was applied to the construction of the PACG classification model. Results: Compared with the HC group, ALFF was attenuated in right posterior thalamic radiation (include optic radiation), splenium of corpus callosum, and left tapetum in the PACG group, the results are statistically significant (GRF correction, voxel-level P < 0.001, cluster-level P < 0.05). Furthermore, the SVM classification had an accuracy of 80.0% and an area under the curve (AUC) of 0.86 for distinguishing patients with PACG from HC. Conclusion: The findings of our study uncover abnormal WM functional alterations in PACG patients and mainly involves vision-related regions. These findings provide new insights into widespread brain damage in PACG from an alternative WM functional perspective.

DNA-methylome-derived epigenetic fingerprint as an immunophenotype indicator of durable clinical immunotherapeutic benefits in head and neck squamous cell carcinoma.

BACKGROUND: Cancer immunotherapy provides durable response and improves survival in a subset of head and neck squamous cell carcinoma (HNSC) patients, which may due to discriminative tumor microenvironment (TME). Epigenetic regulations play critical roles in HNSC tumorigenesis, progression, and activation of functional immune cells. This study aims to identify an epigenetic signature as an immunophenotype indicator of durable clinical immunotherapeutic benefits in HNSC patients. METHODS: Unsupervised consensus clustering approach was applied to distinguish immunophenotypes based on five immune signatures in The Cancer Genome Atlas (TCGA) HNSC cohort. Two immunophenotypes (immune 'Hot' and immune 'Cold') that had different TME features, diverse prognosis, and distinct DNA methylation patterns were recognized. Immunophenotype-related methylated signatures (IPMS) were identified by the least absolute shrinkage and selector operation algorithm. Additionally, the IPMS score by deconvolution algorithm was constructed as an immunophenotype classifier to predict clinical outcomes and immunotherapeutic response. RESULTS: The 'Hot' HNSC immunophenotype had higher immunoactivity and better overall survival (p = 0.00055) compared to the 'Cold' tumors. The immunophenotypes had distinct DNA methylation patterns, which was closely associated with HNSC tumorigenesis and functional immune cell infiltration. 311 immunophenotype-related methylated CpG sites (IRMCs) was identified from TCGA-HNSC dataset. IPMS score model achieved a strong clinical predictive performance for classifying immunophenotypes. The area under the curve value (AUC) of the IPMS score model reached 85.9% and 89.8% in TCGA train and test datasets, respectively, and robustness was verified in five HNSC validation datasets. It was also validated as an immunophenotype classifier for predicting durable clinical benefits (DCB) in lung cancer patients who received anti-PD-1/PD-L1 immunotherapy (p = 0.017) and TCGA-SKCM patients who received distinct immunotherapy (p = 0.033). CONCLUSIONS: This study systematically analyzed DNA methylation patterns in distinct immunophenotypes to identify IPMS with clinical prognostic potential for personalized epigenetic anticancer approaches in HNSC patients. The IPMS score model may serve as a reliable epigenome prognostic tool for clinical immunophenotyping to guide immunotherapeutic strategies in HNSC.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.

SHMT2 Mediates Small-Molecule-Induced Alleviation of Alzheimer Pathology Via the 5'UTR-dependent ADAM10 Translation Initiation.

It is long been suggested that one-carbon metabolism (OCM) is associated with Alzheimer's disease (AD), whereas the potential mechanisms remain poorly understood. Taking advantage of chemical biology, that mitochondrial serine hydroxymethyltransferase (SHMT2) directly regulated the translation of ADAM metallopeptidase domain 10 (ADAM10), a therapeutic target for AD is reported. That the small-molecule kenpaullone (KEN) promoted ADAM10 translation via the 5' untranslated region (5'UTR) and improved cognitive functions in APP/PS1 mice is found. SHMT2, which is identified as a target gene of KEN and the 5'UTR-interacting RNA binding protein (RBP), mediated KEN-induced ADAM10 translation in vitro and in vivo. SHMT2 controls AD signaling pathways through binding to a large number of RNAs and enhances the 5'UTR activity of ADAM10 by direct interaction with GAGGG motif, whereas this motif affected ribosomal scanning of eukaryotic initiation factor 2 (eIF2) in the 5'UTR. Together, KEN exhibits therapeutic potential for AD by linking OCM with RNA processing, in which the metabolic enzyme SHMT2 "moonlighted" as RBP by binding to GAGGG motif and promoting the 5'UTR-dependent ADAM10 translation initiation.

Altered functional connectivity between the default mode network in primary angle-closure glaucoma patients.

Previous studies have recognized glaucoma as a neurodegenerative disease that causes extensive brain damage and is closely associated with cognitive function. In this study, we employed functional MRI to examine the intrinsic functional connectivity patterns of the default mode network (DMN) in patients diagnosed with primary angle-closure glaucoma (PACG), exploring its association with cognitive dysfunction. A total of 34 patients diagnosed with PACG and 34 healthy controls (HC), who were matched in terms of sex, age, and education, were included in the control group. The posterior cingulate cortex (PCC) was selected as the region of interest to examine functional connectivity alterations. Compared with the HC group, functional connectivity was attenuated in left anterior cingulum cortex and left paracentral lobule between with PCC in the PACG group, the results are statistically significant. Our study revealed that patients with PACG exhibit weakened functional connectivity within the DMN. This finding suggests the presence of a neurological mechanism that is associated with both visual dysfunction and cognitive impairments in PACG patients. Furthermore, our study provides neuroimaging evidence that can aid in the exploration of spontaneous neurological alterations and facilitate a deeper investigation of alterations in the visual conduction pathways of PACG patients.

Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease.

The purpose of this study was to examine the characteristics of proximal and distal gastroesophageal reflux in patients with gastroesophageal reflux disorder and analyze their clinical symptoms. A total of 67 patients with typical esophageal symptoms were selected for this study. All participants completed the reflux disease questionnaire and a questionnaire survey of extraesophageal symptoms. Diagnosis was made using a 24-h impedance-pH detection and proton pump inhibitor. The results showed that the proximal reflux group had a higher number of acid reflux episodes compared to the distal reflux group (P < 0.05). Similarly, the proximal reflux group also had a higher number of gas reflux episodes compared to the distal reflux group (P < 0.05). On the other hand, the distal reflux group had a higher number of mixed reflux episodes compared to the proximal reflux group (P < 0.05). These differences were statistically significant. This study revealed that acid reflux and gas reflux were more predominant in the proximal reflux group, while mixed reflux was more predominant in the distal reflux group.

[Effects of Polystyrene Microplastics on Growth, Physiology, Biochemistry, and Canopy Temperature Characteristics of Chinese Cabbage Pakchoi (Brassica chinensis L.)].

The aim of this study was to clarify the response characteristics of Chinese cabbage pakchoi (Brassica chinensis L.) under two particle size (100 nm and 1000 nm) polystyrene microplastic (PS-MPs) stress conditions. This study can provide a theoretical basis and experimental reference for the interpretation of the physiological and ecological mechanism of microplastic pollution and the bioremediation of microplastic-contaminated soil. Hydroponic experiments were carried out to study the effects of two particle sizes (100 nm and 1000 nm) of PS-MPs on growth, photosynthetic physiology, antioxidant enzyme activities, nutritional quality, anatomical structure, and canopy temperature in Chinese cabbage pakchoi. The results showed that PS-MPs stress significantly inhibited the growth and development of Chinese cabbage pakchoi. When PS-MPs stress was increased, the phenotypic indicators were significantly reduced. Meanwhile, PS-MPs stress significantly enhanced the oxidative stress response of Chinese cabbage pakchoi, such as the activities of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX) and the content of malondialdehyde (MDA) in leaves. Such a change tended to decrease the thickness of fenestrated and leaf and spongy tissues. Moreover, PS-MPs stress significantly increased the canopy population temperature of the Chinese cabbage pakchoi leaves. Microplastic stress had obvious inhibitory effects and toxic damage on the growth, development, and physical and chemical properties of Chinese cabbage pakchoi.

[Modulation of autophagy in the rats with acute intracerebral hemorrhage by acupuncture based on JNK pathway].

OBJECTIVE: To investigate the effects of acupuncture on JNK pathway and autophagy level in rats with intracerebral hemorrhage （ICH） and explore the partial mechanism of acupuncture against ICH. METHODS: SD rats were randomly divided into blank group, model group and acupuncture group. Each group was divided into Day 1, Day 3 and Day 7 subgroups respectively, with 5 rats in each group. The autologous blood injection was adopted to duplicate rat model of ICH. In the acupuncture group, the needle was inserted from "Baihui" （GV20） towards "Qubin" （GB7） on the affected side, stimulating for 30 min each time, once daily； the same acupuncture technique was opera-ted in each subgroup for 1, 3 and 7 days, separately. Using Bederson scale, the neurological deficit was evaluated in each group. Western blot was adopted to detect the protein expression levels of Beclin1, LC3Ⅰ/Ⅱ, phosphorylated c-Jun amino-terminal kinase （p-JNK） and the phosphorylated （p）-c-Jun around hematoma lesion of the brain tissue of rats in each group. RESULTS: After treatment, the neurological deficit score of rats in the model group was higher than that of the blank group at each time point （P<0.05）, and the score of the acupuncture group started declining since the 3rd day of treatment when compared with the model group （P<0.05）. At each time point, compared with the blank group, the protein expression levels of LC3Ⅰ/Ⅱ, Beclin1, p-c-Jun and p-JNK was increased （P<0.01）. Compared with the model group, the protein expression level of LC3Ⅰ/Ⅱ was reduced （P<0.05）； the protein expression levels of Beclin1, p-c-Jun and p-JNK was increased （P<0.05, P<0.01） on day 3 and 7 in the acupuncture group. CONCLUSION: Acupuncture can activate the JNK pathway in the brain tissue of rats with ICH and increase the level of autophagy, thereby improving the neurological function of the rats with ICH.

N-acetylcysteine ameliorates erectile dysfunction in rats with hyperlipidemia by inhibiting oxidative stress and corpus cavernosum smooth muscle cells phenotypic modulation.

Hyperlipidemia is a major risk factor for erectile dysfunction (ED). Oxidative stress and phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) are the key pathological factors of ED. N-acetylcysteine (NAC) can inhibit oxidative stress; however, whether NAC can alleviate pathological variations in the corpus cavernosum and promote erectile function recovery in hyperlipidemic rats remains unclear. A hyperlipidemia model was established using 27 eight-week-old male Sprague-Dawley (SD) rats fed a high-fat and high-cholesterol diet (hyperlipidemic rats, HR). In addition, 9 male SD rats were fed a normal diet to serve as controls (NC). HR rats were divided into three groups: HR, HR+normal saline (NS), and HR+NAC (n = 9 for each group; NS or NAC intraperitoneal injections were administered daily for 16 weeks). Subsequently, the lipid profiles, erectile function, oxidative stress, phenotypic modulation markers of CCSMCs, and tissue histology were analyzed. The experimental results revealed that erectile function was significantly impaired in the HR and HR + NS groups, but enhanced in the HR + NAC group. Abnormal lipid levels, over-activated oxidative stress, and multi-organ lesions observed in the HR and HR + NS groups were improved in the HR + NAC group. Moreover, the HR group showed significant phenotypic modulation of CCSMCs, which was also inhibited by NAC treatment. This report focuses on the therapeutic effect of NAC in restoring erectile function using a hyperlipidemic rat model by preventing CCSMC phenotypic modulation and attenuating oxidative stress.

cdh23 affects congenital hearing loss through regulating purine metabolism.

Introduction: The pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown. Methods: In this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23, subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23-/-. To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed. Results: The YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23. RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23-/- embryos can partially recover the mutant phenotype. Conclusion: In conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.

Network pharmacology, molecular docking and experimental verification help unravel chelerythrine's potential mechanism in the treatment of gastric cancer.

Gastric cancer (GC) is a deadly malignant tumor with a high fatality rate and limited curative options. A growing body of research suggests that network pharmacology can replace traditional methods for determining the precise mechanism of action of medicinal substances in conditions such as cancer. The goal of this study was to clarify the biological mechanism of chelerythrine (CHE) and develop a prediction target for CHE against GC using network pharmacology. First, the genes related to GC were identified from the databases Genecards, Disgenet, Online Mendelian Inheritance in Man, Therapeutic Target Database, and Drugbank, and the targets of CHE were obtained from the SwissTargetPrediction database. Fifty linked targets were identified as anti-GC targets of CHE. Functional enrichment and pathway analyses revealed important biological mechanisms mediated by these targets. The core target PIK3CA of CHE anti-GC was obtained using the protein-protein interaction network, CytoHubba plug-in, and Human Protein Atlas. Molecular docking studies revealed that CHE has a strong affinity for PIK3CA (-10.5 kcal/mol). In addition, we used MTT, colony formation, wound-healing, Transwell®, and flow cytometry experiments to confirm that CHE inhibited the proliferation and migration of GC cells and induced cell cycle arrest and apoptosis. Finally, western blotting results showed that CHE downregulated the expression of the PIK3CA protein and inhibited the activation of the PI3K/AKT signaling pathway. Therefore, we concluded that CHE inhibited GC cell proliferation and migration and induced cell cycle arrest and apoptosis by targeting the PIK3CA protein to inhibit the PI3K/AKT pathway activity.

Comparisons of artificial intelligence algorithms in automatic segmentation for fungal keratitis diagnosis by anterior segment images.

Purpose: This study combines automatic segmentation and manual fine-tuning with an early fusion method to provide efficient clinical auxiliary diagnostic efficiency for fungal keratitis. Methods: First, 423 high-quality anterior segment images of keratitis were collected in the Department of Ophthalmology of the Jiangxi Provincial People's Hospital (China). The images were divided into fungal keratitis and non-fungal keratitis by a senior ophthalmologist, and all images were divided randomly into training and testing sets at a ratio of 8:2. Then, two deep learning models were constructed for diagnosing fungal keratitis. Model 1 included a deep learning model composed of the DenseNet 121, mobienet_v2, and squeezentet1_0 models, the least absolute shrinkage and selection operator (LASSO) model, and the multi-layer perception (MLP) classifier. Model 2 included an automatic segmentation program and the deep learning model already described. Finally, the performance of Model 1 and Model 2 was compared. Results: In the testing set, the accuracy, sensitivity, specificity, F1-score, and the area under the receiver operating characteristic (ROC) curve (AUC) of Model 1 reached 77.65, 86.05, 76.19, 81.42%, and 0.839, respectively. For Model 2, accuracy improved by 6.87%, sensitivity by 4.43%, specificity by 9.52%, F1-score by 7.38%, and AUC by 0.086, respectively. Conclusion: The models in our study could provide efficient clinical auxiliary diagnostic efficiency for fungal keratitis.

Dipicolinic acid enhances kiwifruit resistance to Botrytis cinerea by promoting phenolics accumulation.

BACKGROUND: Kiwifruit is highly susceptible to fungal pathogens, such as Botrytis cinerea, which reduce crop production and quality. In this study, dipicolinic acid (DPA), which is one of the main components of Bacillus spores, was evaluated as a new elicitor to enhance kiwifruit resistance to B. cinerea. RESULTS: DPA enhances antioxidant capacity and induces the accumulation of phenolics in B. cinerea-infected 'Xuxiang' kiwifruit. The contents of the main antifungal phenolics in kiwifruit, including caffeic acid, chlorogenic acid and isoferulic acid, increased after DPA treatment. DPA enhanced H2 O2 levels after 0 and 1 days, which promoted catalase (CAT) and superoxide dismutase (SOD) activities, reducing long-term H2 O2 levels. DPA promoted the up-regulation of several kiwifruit defense genes, including CERK1, MPK3, PR1-1, PR1-2, PR5-1 and PR5-2. Furthermore, DPA at 5 mM inhibited B. cinerea symptoms in kiwifruit (95.1% lesion length inhibition) more effectively than the commercial fungicides carbendazim, difenoconazole, prochloraz and thiram. CONCLUSIONS: The antioxidant properties of DPA and the main antifungal phenolics of kiwifruit were examined for the first time. This study uncovers new insights regarding the potential mechanisms used by Bacillus species to induce disease resistance. © 2023 Society of Chemical Industry.

Altered dynamic functional connectivity in the primary visual cortex in patients with primary angle-closure glaucoma.

Purpose: Glaucoma is the main blindness-causing disease in the world. Previous neuroimaging studies demonstrated that glaucoma not only causes the loss of optic ganglion cells but also leads to the abnormal function of the optic nerve pathway and the visual cortex. However, previous studies also reported that patients with glaucoma have dysfunction in the visual cortex in a static state. Whether or not patients with primary angle-closure glaucoma (PACG) were accompanied by dynamic functional connectivity (FC) changes in the primary visual cortex (V1) remains unknown. Methods: A total of 34 patients with PACG (23 men and 11 women) and 34 well-matched healthy controls (HCs) were enrolled in the study. The dynamic functional connectivity (dFC) with the sliding window method was applied to investigate the dynamic functional connectivity changes in the V1. Results: Compared with HCs, patients with PACG showed increased dFC values between left V1 and bilateral calcarine (CAL). Meanwhile, patients with PACG showed increased dFC values between right V1 and bilateral CAL. Conclusion: Our study demonstrated that patients with PACG showed increased dFC within the visual network, which might indicate the increased variability FC in the V1 in patients with PACG.

Transcriptional regulation of host insulin signaling pathway genes controlling larval development by Microplitis manilae parasitization.

Idiobiont parasitoids using other insects as hosts sabotage the host growth and development to ensure their offspring survival. Numerous studies have discovered that insect development is subtly regulated by the conserved insulin signaling pathway. However, little is known about how wasp parasitization disrupts host development controlled by the insulin signaling pathway. Here we address this study to determine the effect of wasp parasitism on host Spodoptera frugiperda development using the idiobiont parasitoid Microplitis manilae as a model. Upon M. manilae parasitization, the body weight, body length, and food consumption of host insect were dramatically reduced compared to the unparasitized S. frugiperda. We next identified the core genes involved in host insulin signaling pathway and further analyzed the domain organizations of these genes. Phylogenetic reconstruction based on the insulin receptors clustered S. frugiperda together with other noctuidae insects. In the latter study, we profiled the expression patterns of host insulin signaling pathway genes in response to M. manilae parasitization at 2, 24, and 48 h, significant decreases in mRNA levels were recorded in S. frugiperda larvae upon 24 and 48 h parasitization. These current findings substantially add to our understanding of the physiological interaction between parasitoid and host insects, thus contributing to revealing the molecular mechanism of parasitic wasps regulating host development.

Warm acupuncture therapy alleviates neuronal apoptosis after spinal cord injury via inhibition of the ERK signaling pathway.

PURPOSE: Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: The rat SCI models were established by the impact method. SCI rat models were subjected to WA treatment at Dazhui (GV14) and Jiaji points (T10), Yaoyangguan (GV3), Zusanli (ST36), and Ciliao (BL32). The rat SCI models were established by the impact method. WA and U0126 treatments were performed on the SCI rats. Motor function and neuronal apoptosis were detected. The relative mRNA of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), the phosphorylation level of ERK 1/2 and levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and caspase-3 in spinal cord tissue were tested. RESULTS: After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI. CONCLUSION: Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.

Seasonal Variation of Hypolithic Microbiomes in the Gobi Desert : Seasonal Variation of Hypolithic Microbiomes in the Gobi Desert.

Understanding how microbial communities adapt to environmental stresses is critical for interpreting ecological patterns and microbial diversity. In the case of the Gobi Desert, little is known on the environmental factors that explain hypolithic colonization under quartz stones. By analyzing nine hypolithic communities across an arid gradient and the effects of the season of the year in the Hexi Corridor of this desert, we found a significant decrease in hypolithic colonization rates (from 47.24 to 15.73%) with the increasing drought gradient and found two distinct communities in Hot and Cold samples, which survived or proliferated after a hot or a cold period. While Cold communities showed a greater species diversity and a predominance of Cyanobacteria, Hot communities showed a predominance of members of the Proteobacteria and the Firmicutes. In comparison, Cold communities also possessed stronger functions in the photosynthesis and carbon metabolism. Based on the findings of this study, we proposed that the hypolithic communities of the Hexi Corridor of the Gobi Desert might follow a seasonal developmental cycle in which temperature play an important role. Thus after a critical thermal threshold is crossed, heterotrophic microorganisms predominate in the hot period, while Cyanobacteria predominate in the cold period.

Diquafossol sodium combined with Qingrun Yangmu oral liquid for the treatment of dry eye after cataract operation / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of diquafosol sodium(DQS)eye drops combined with Qingrun Yangmu oral liquid in the treatment of dry eye after phacoemulsification and intraocular lens implantation.METHODS:A total of 57 patients(65 eyes)with dry eye after cataract surgery, who were admitted to the ophthalmology department of our hospital from September 2020 to January 2021, were selected as the research objects. They were divided into a control group(28 cases, 32 eyes, treated with 3% DQS eye drops)and an observation group(29 cases, 33 eyes, treated with 3% DQS eye drops combined with the Qingrun Yangmu oral liquid)based on a random number table method. Indicators, such as ocular surface disease index(OSDI), non-invasive tear film break-up time(NIBUT), Schirmer I test(SIt), corneal fluorescein sodium staining(CFS), and TCM symptom score, were compared and analyzed between the two groups 1d before, 1wk after(before treatment), and 1mo after(after treatment)surgery.RESULTS:The total effective rates of the observation group and the control group after treatment were 88% and 75%, respectively. The OSDI, NIBUT and SIt of the two groups after treatment showed significant improvement compared to those before treatment(P&#x003C;0.05). The NIBUT, SIt, CFS, and TCM symptom scores of the observation group after treatment were better than those of the control group(P&#x003C;0.05). No adverse reactions were observed in both groups.CONCLUSION:Combined use of DQS eye drops and the Qingrun Yangmu oral liquid can improve symptoms and clinical indicators of dry eye after cataract surgery, providing a new treatment method for ocular surface management of dry eye during the perioperative period of cataract surgery.

Circular RNA circRSF1 binds to HuR to promote radiation-induced inflammatory phenotype in hepatic stellate cells / 南方医科大学学报

OBJECTIVE@#To investigate whether circular RNA circRSF1 regulates radiation-induced inflammatory phenotype of hepatic stellate cells (HSCs) by binding to HuR protein and repressing its function.@*METHODS@#Human HSC cell line LX2 with HuR overexpression or knockdown was exposed to 8 Gy X-ray irradiation, and the changes in the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) were detected by qRT-PCR. The expressions of IκBα and phosphorylation of NF-κB were detected with Western blotting. The binding of circRSF1 to HuR was verified by RNA pull-down assay and RNA-binding protein immunoprecipitation (RIP). The expressions of inflammatory factors, IκBα and the phosphorylation of NF-κB were detected after modifying the interaction between circRSF1 and HuR.@*RESULTS@#Knockdown of HuR significantly up- regulated the expressions of IL-1β, IL-6 and TNF-α, decreased IκBα expression and promoted NF-κB phosphorylation in irradiated LX2 cells, whereas overexpression of HuR produced the opposite changes (P < 0.05). Overexpression or knockdown of circRSF1 did not significantly affect the expression of HuR. RNA pull-down and RIP experiments confirmed the binding between circRSF1 and HuR. Overexpression of circRSF1 significantly reduced the binding of HuR to IκBα and down-regulated the expression of IκBα (P < 0.05). Overexpression of circRSF1 combined with HuR overexpression partially reversed the up-regulation of the inflammatory factors, down-regulated IκBα expression and increased phosphorylation of NFκB in LX2 cells, while the opposite effects were observed in cells with knockdown of both circRSF1 and HuR (P < 0.05).@*CONCLUSION@#circRSF1 reduces IκBα expression by binding to HuR to promote the activation of NF-κB pathway, thereby enhancing radiation- induced inflammatory phenotype of HSCs.