Transplantation of insulin-producing cells derived from human MSCs to treat diabetes in a non-human primate model.

BACKGROUND: Islet cell transplantation is an emerging therapy in the treatment of diabetes mellitus. Differentiation of islet cells from mesenchymal stem cells (MSCs) is a potential solution to the challenge of insufficient donor sources. This study investigated whether human umbilical cord-derived MSCs could effectively differentiate into insulin-producing cells (IPCs) and evaluated the therapeutic efficacy of IPCs in treating diabetes. METHODS: IPCs were induced from MSCs by a two-step protocol. IPC expression products were evaluated by western blot and real-time PCR. IPC insulin secretion was evaluated by ELISA. The viability of IPCs was measured by FDA/PI and dithizone staining. The non-human primate tree shrew was used as a diabetes model. After a single STZ induction into a diabetes model, a single intraportal transplantation of IPCs, MSCs, or normal saline was performed (n = 6 per group). Blood glucose was monitored for 3 weeks, then the animals were euthanized and the distribution of IPCs in the liver was examined pathologically. RESULTS: After about 3 weeks of in vitro induction, IPCs formed microspheres of 100-200 µm, with >95% viable cells that were dithizone stain positive. IPCs expressed islet-related genes and proteins and secreted high levels of insulin whether stimulated by low or high levels of glucose. After transplantation of IPCs into diabetic tree shrews, blood glucose levels decreased rapidly to near normal and were significantly lower than the MSC or saline groups for 3 weeks thereafter. CONCLUSION: We present the novel discovery that IPCs derived from human umbilical cord MSCs exert a therapeutic effect in a non-human primate model of diabetes. This study provides a preliminary experimental basis for the use of autologous MSC-derived IPCs in the treatment of human diabetes.

Retracted: Anticancer Activity of Mukonal Against Human Laryngeal Cancer Cells Involves Apoptosis, Cell Cycle Arrest, and Inhibition of PI3K/AKT and MEK/ERK Signalling Pathways.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. Reference: Liu Li, Lu Huizhi, Wang Binu, Deng Xinxin, Wu Longjun, Yang Liping, Zhang Yingying. Anticancer Activity of Mukonal Against Human Laryngeal Cancer Cells Involves Apoptosis, Cell Cycle Arrest, and Inhibition of PI3K/AKT and MEK/ERK Signalling Pathways. Med Sci Monit, 2018; 24: 7295-7302. DOI: 10.12659/MSM.910702.

The changes in bone turnover markers of female systemic lupus erythematousus patients without glucocorticoid.

OBJECTIVES: SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. METHODS: A total of 865 female subjects were recruited from Zhejiang Provincial People's Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of ß - I collagen (ß-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. RESULTS: In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and ß-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of ß-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, ß-CTX reached a high value in summer and PINP reached a low value in winter. CONCLUSION: The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.

Anticancer Activity of Mukonal Against Human Laryngeal Cancer Cells Involves Apoptosis, Cell Cycle Arrest, and Inhibition of PI3K/AKT and MEK/ERK Signalling Pathways.

BACKGROUND Laryngeal cancer is one of the major malignancies of the neck and head and is responsible for considerable mortality across the globe. The treatments for laryngeal cancer mainly involve surgical interventions followed by chemotherapy. However, due to unsatisfactory results, constant relapses and the adverse effects associated with the currently used drugs, there is pressing need to develop effective drug options for treatment of laryngeal cancer. Therefore, this study was undertaken to investigate the anticancer effects of a plant-derived alkaloid, Mukonal, against human AMC-HN-8 laryngeal cancer cells. MATERIAL AND METHODS The WST-1 and clonogenic assays were employed to determine the cell viability. Apoptosis was detected by Hoechst and AO/EB staining. Cell migration and cell cycle analysis was performed by Transwell assay and flow cytometry, respectively. Protein expression was examined by Western blotting. RESULTS The results revealed that Mukonal reduced the viability of laryngeal cancer cells dose-dependently. The IC50 of Mukonal was found to be 10 µM. However, the effects of Mukonal on the normal HuLa-PC cells was found to be 140 µM. The decrease in the viability of the AMC-HN-8 laryngeal cancer cells was found to be due to the induction of apoptosis and G2/M cell cycle arrest. Mukonal also suppressed the cell migration and of the AMC-HN-8 laryngeal cancer cells. Mukonal could also inhibit the PI3K/AKT and MEK/ERK signalling pathways in a concentration-dependent manner. CONCLUSIONS Taken together, we conclude that Mukonal could prove a beneficial lead molecule for the treatment of laryngeal cancer.

Exosomal-microRNAs Improve Islet Cell Survival and Function In Islet Transplantation.

Exosomal-microRNAs (Exo-miRNAs) are key regulators of islet cell function, including insulin expression, processing, and secretion. Exo-miRNAs have a significant impact on the outcomes of islet transplantation as biomarkers for evaluating islet cell function and survival. Furthermore, they have been linked to vascular remodeling and immune regulation following islet transplantation. Mesenchymal stem cell-derived exosomes have been shown in preliminary studies to improve islet cell viability and function when injected or transplanted into mice. Overall, Exo-miRNAs have emerged as novel agents for improving islet transplantation success rates. The role of islet-derived Exo-miRNAs and mesenchymal stem cells-derived Exo-miRNAs as biomarkers and immunomodulators in islet regeneration, as well as their role in improving islet cell viability and function in islet transplantation, are discussed in this review.

The role of orthographic and phonological processing during reading Chinese sentences: Evidence from eye movements.

The role of phonological and orthographic processing and their time course during lexical processing and sentence reading remain controversial. By adopting a misspelled-characters disruption paradigm and eye-tracking technique, we manipulated the writing for the first characters of two-character target words to investigate the relative role of orthographic and phonological processing on word recognition in Chinese reading. There are four conditions: (a) correct character, (b) misspelled character with a stroke missing, (c) misspelled homographic character, and (d) misspelled homophonic character. The results showed that homophonic errors caused more disruptions than other conditions in the early (first-pass reading times) and later (total reading time) stages of lexical processing during Chinese reading. Homographic errors and omitted stroke errors lead to equal disruptions at the early stage of word recognition, but homographic errors cause more disruptions at the later stage. These results suggest that orthography plays a dominant role in word recognition during Chinese reading, whereas phonology plays a weaker and more limited role. The direct access and dual-rote hypothesis may well explain the mechanism of lexical processing in Chinese reading.

Effectiveness and safety of Pingxiao capsule as adjuvant therapy in treatment of breast cancer: a systematic review and Meta-analysis.

OBJECTIVE: To systematically review the effectiveness and safety of Pingxiao capsule adjuvant chemotherapy in the treatment of breast cancer. METHODS: A total of 8 databases including the Cochrane Library, PubMed, EMBASE, Engineering Index, Chinese Biomedical Literature Database, Wanfang database, China National Knowledge Infrastructure Database, and China Science and Technology Journal Database were searched for the Randomized Controlled Trials (RCTs) of Pingxiao capsule combined with chemotherapy in the treatment of breast cancer published before June 2022. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. R language was used for estimating risks of bias of included studies, data analysis, and plotting. RESULTS: A total of 15 RCTs involving 1272 patients were included in this study. Meta-analysis results indicated that compared with chemotherapy alone, Pingxiao capsule combined with chemotherapy could significantly improve breast cancer patients' objective response rate of breast cancer patients [rate ratio () = 1.35, 95% confidence interval () (1.12, 1.63), = 0.0017], the disease control rate [=1.16, 95% (1.08, 1.25), < 0.0001], the quality of life [ =1.42, 95% (1.16, 1.74), = 0.007], and the level of the immune cells [CD3+: standardized mean difference () =1.42, 95% (0.76, 2.09), < 0.001; CD4+: =1.18, 95% (0.70, 1.66), < 0.001]. In addition, Pingxiao capsule combined with chemotherapy can also significantly reduce CD8+ level ( < 0.0001) and reduce the symptoms of decreased white blood cell count [ = 0.62, 95% (0.39, 0.85), < 0.0001], and the occurrence of adverse reactions such as gastrointestinal adverse reactions and limb pain ( < 0.05). CONCLUSIONS: Pingxiao capsule can significantly improve the efficacy of chemotherapy, the quality of life and immune function of patients, and reduce the clinical side effects caused by chemotherapy. However, high-quality randomized clinical trials with large samples are required for further verification of these results.

The phenotypic variation mechanisms of Atractylodes lancea post-cultivation revealed by conjoint analysis of rhizomic transcriptome and metabolome.

The wild Atractylodes lancea rhizomes have been traditionally used as herbal medicine. As the increasingly exhaustion of wild A. lancea, the artificial cultivation mainly contributed to the medicinal material production. However, besides the phenotypic variation of rhizome phenotypic trait alteration, the qualities of cultivated A. lancea decrease compared with the wild counterpart. To unveil the physiological and molecular mechanism beneath the phenotypic variation, GC-MS-based volatile organic compounds (VOCs) profiling and RNAseq-based transcriptome analysis were conducted. The volatile metabolomics profiling revealed 65 differentially accumulated metabolites (DAMs) while the transcriptomic profiling identified 12 009 differentially expressed unigenes (DEGs) post-cultivation. The volatile active compounds including atractylone, and eudesmol accumulated more in wild rhizome than in the cultivated counterpart, and several unigenes in terpene synthesis were downregulated under cultivated condition. Compared with the wild A. lancea rhizome, the contents of bioactive Jasmonic Acid (JAs) in cultivated A. lancea rhizome were higher, and evidences that JAs negatively regulate the terpenes biosynthesis in the cultivated A. lancea rhizome were also provided. The combinational omics analysis further indicated the high correlation between the ten cultivation-suppressed VOCs and the cultivation-altered genes for sesquiterpenoids biosynthesis in A. lancea. The network of the cultivation-altered transcription factors (TFs) and the ten VOCs suggested TFs (e.g. Arabidopsis ERF13 homologs and WRKY50) are involved in the regulation of terpenes biosynthesis. These results laid a theoretical basis for developing geo-herbalism medicinal plants with "high quality and optimal shape".

Exosomal microRNAs as diagnostic biomarkers and therapeutic applications in neurodegenerative diseases.

Originating from slow irreversible and progressive loss and dysfunction of neurons and synapses in the nervous system, neurodegenerative diseases (NDDs) affect millions of people worldwide. Common NDDs include Parkinson's disease, Alzheimer's disease multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Currently, no sensitive biomarkers are available to monitor the progression and treatment response of NDDs or to predict their prognosis. Exosomes (EXOs) are small bilipid layer-enclosed extracellular vesicles containing numerous biomolecules, including proteins, nucleic acids, and lipids. Recent evidence indicates that EXOs are pathogenic participants in the spread of neurodegenerative diseases, contributing to disease progression and spread. EXOs are also important tools for diagnosis and treatment. Recently, studies have proposed exosomal microRNAs (miRNAs) as the targets for therapies or biomarkers of NDDs. In this review, we outline the latest research on the roles of exosomal miRNAs in NDDs and their applications as potential diagnostic and therapeutic biomarkers, targets, and drugs for NDDs.

Toxic effect of BDE-47 on the marine alga Skeletonema costatum: Population dynamics, photosynthesis, antioxidation and morphological changes.

The toxic effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on the marine alga Skeletonema costatum were studied, including the population dynamics, chlorophyll fluorescence characteristics, pigment content, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and morphology. High doses (200-600 µg L-1) of BDE-47 significantly suppressed the population growth of S. costatum, with a 96 h EC50 value of 293 µg L-1. Photosynthetic parameters (Fv/Fm, rETRmax and ΦPSⅡ) of photosystem II (PSII) were significantly inhibited with increasing BDE-47 concentrations. The chlorophyll c (chl c) concentration was also inhibited by exposure to BDE-47. In contrast, chl a and carotenoid concentrations were elevated after exposure to high concentrations of BDE-47 for 72 and 96 h. The SOD activity was generally higher at concentrations of 100-600 µg L-1 than those of the control when the exposure time was less than 48 h. With increasing time, the SOD activity generally decreased, and significantly higher SOD activity only occurred in the treatment with high doses of BDE-47. High MDA contents occurred after exposure for 96 h in all BDE-47 treatments. With increasing BDE-47 concentrations, drastic deformation of the silicious valve and detachment of the strutted processes were found. In addition, drastic decreases in the BDE-47 concentration in culture medium indicated the bioaccumulation of BDE-47 by S. costatum. Our results revealed multiple responses of S. costatum to BDE-47 exposure, and indicated the potential risk of BDE-47 in the East China Sea based on these responses.

Determination of effective complex refractive index of a turbid liquid with surface plasmon resonance phase detection.

The dependence of the surface plasmon resonance (SPR) phase difference curve on the complex refractive index of a sample in Kretschmann configuration is discussed comprehensively, based on which a new method is proposed to measure the complex refractive index of turbid liquid. A corresponding experiment setup was constructed to measure the SPR phase difference curve, and the complex refractive index of turbid liquid was determined. By using the setup, the complex refractive indices of Intralipid solutions with concentrations of 5%, 10%, 15%, and 20% are obtained to be 1.3377+0.0005 i, 1.3427+0.0028 i, 1.3476+0.0034 i, and 1.3496+0.0038 i, respectively. Furthermore, the error analysis indicates that the root-mean-square errors of both the real and the imaginary parts of the measured complex refractive index are less than 5x10(-5).

Expression and Clinical Value of Serum miR-4429 and miR-19-3p in Patients with Pelvic Floor Dysfunctional Disease / 现代检验医学杂志

Objective To investigate the expression and significance of microRNA(miR)-4429 and microRNA(miR)-19-3p level in patients with pelvic floor dysfunctional(PFD)disease.Methods A total of 90 PFD patients admitted to the Second People's Hospital of Hengshui from June 2021 to June 2022 were selected as the PFD group.They were grouped into the pelvic organ prolapse(POP)group(n=50),the stress urinary incontinence(SUI)group(n=25),and the POP combined with SUI group(n=15).Meanwhile,80 healthy women who were examined in the Second People's Hospital of Hengshui were collected as the control group.The general data such as delivery mode,previous abortion history and family history were compared between the control group and the PFD group.The levels of serum miR-4429 and miR-19-3p in each group were compared.The diagnostic value of serum miR-4429 and miR-19-3p levels in PFD was analyzed by receiver operating characteristic(ROC)analysis.Logistic regression analysis was applied to analyze the factors affecting PFD.The paired sample t-test was applied to compare the changes in serum miR-4429 and miR-19-3p levels before and after PFD treatment.Results There were significant differences between the PFD group and the control group in terms of delivery mode,previous abortion history,and PFD family history,and the differences were statistically significant(t=4.415,6.444,4.707,all P＜0.05).The serum miR-4429(0.71±0.19 vs 1.00±0.25)level in the PFD group was lower than that in the control group,while the miR-19-3p(1.44±0.35 vs 1.01±0.28)level was higher than that in the control group,and the differences was statistically significant(t=8.927,8.772,all P＜0.05).The serum miR-4429(0.73±0.22,0.74±0.16 vs 0.59±0.16)level in the POP and SUI groups was higher than that in the POP combined SUI group,while the serum miR-19-3p(1.35±0.39,1.41±0.31 vs 1.77±0.56)level in the POP group and SUI group was lower than that in the POP combined with SUI group,with significant differences(t=3.531,3.411;5.003,3.865,all P＜0.05).ROC analysis showed that the areas under curve(AUC)for miR-4429 and miR-19-3p to assist in assessing whether PFD occurs were 0.805 and 0.825,respectively.The AUC of the combined detection was 0.865.Multivariate logistic regression analysis showed that miR-19-3p was a risk factor affecting PFD,while miR-4429 was a protective factor.After treatment,serum miR-4429(0.93±0.23 vs 0.71±0.19)level in PFD patients increased,while the miR-19-3p(1.12±0.29 vs 1.44±0.35)level decreased,the diffences were statistically significant(t=6.996,6.679,all P＜0.05).Conclusion The serum miR-4429 level in patients with PFD decreased,while the miR-19-3p level increased.The levels of miR-4429 and miR-19-3p in serum were closely related to the occurrence and development of PFD diseases,which can be used as evaluation indicators to predict PFD.

Establishment of nomogram model of acute kidney injury risk prediction based on clinical database / 中华肾脏病杂志

Objective:To construct the risk prediction nomogram model of acute kidney injury (AKI) with R language and traditional statistical methods based on the large sample clinical database, and verify the accuracy of the model.Methods:It was a a retrospective case control study. The patients who met the diagnostic criteria of AKI in Tongji Hospital of Tongji University from January 1 to December 31, 2021 were screened in the clinical database, and the patients with monitored serum creatinine within 48 hours but without AKI were included as the control group. The demographic data, disease history, surgical history, medication history and laboratory test data were collected to screen the risk factors of AKI in clinic.Firstly, based on multivariate logistic regression analysis and forward stepwise logistic regression analysis, the selected risk factors were included to construct the nomogram model. At the same time, cross validation, bootstrap validation and randomly split sample validation were used for internal verification, and clinical data of patients in the sane hospital after one year (January to December, 2022) were collected for external verification. The receiver-operating characteristic curve was used to determine the discrimination of the model, and calibration curve and decision curve analysis were carried out to evaluate the accuracy and clinical net benefit, respectively.Results:A total of 5 671 patients were enrolled in the study, with 1 884 AKI patients (33.2%) and 3 787 non-AKI patients (66.7%). Compared with non-AKI group, age, and proportions of surgical history, renal replacement therapy, hypertension, diabetes, cerebrovascular accident,chronic kidney disease, drug use histories and mortality in AKI group were all higher (all P<0.05). Multivariate logistic regression analysis showed that the independent influencing factors of AKI were surgical history, hypertension, cerebrovascular accident, diabetes, chronic kidney disease, diuretics, nitroglycerin, antidiuretic hormones, body temperature, serum creatinine, C-reactive protein, red blood cells, white blood cells, D-dimer, myoglobin, hemoglobin, blood urea nitrogen, brain natriuretic peptide, aspartate aminotransferase, alanine aminotransferase, triacylglycerol, lactate dehydrogenase, total bilirubin, activated partial thromboplastin time, blood uric acid and potassium ion (all P<0.05). Finally, the predictive factors in the nomogram were determined by forward stepwise logistic regression analysis, including chronic kidney disease, hypertension, myoglobin, serum creatinine and blood urea nitrogen, and the area under the curve of the prediction nomogram model was 0.926 [95% CI 0.918-0.933, P<0.001]. The calibration curve showed that the calibration effect of nomogram was good ( P>0.05). The decision curve showed that when the risk threshold of nomogram model was more than 0.04, the model construction was useful in clinic. In addition, the area under the curve of receiver-operating characteristic curve predicted by nomograph model in external validation set was 0.876 (95% CI 0.865-0.886), which indicated that nomograph model had a high discrimination degree. Conclusion:A nomogram model for predicting the occurrence of AKI is established successfully, which is helpful for clinicians to find high-risk AKI patients early, intervene in time and improve the prognosis.

Clinical value of genetic polymorphism analysis of hypertension drugs for individualized treatment of hypertension patients in the southern Anhui region / 中国临床药理学与治疗学

AIM: To analyze the distribution frequency of gene polymorphisms of β receptor blockers, angiotensin receptor antagonists, angiotensin converting enzyme inhibitors, calcium antagonists, and diuretics in hypertensive patients from southern Anhui province, and provide a theoretical basis for gene detection of hypertension drugs and personalized medication. METHODS: Drug gene testing information from 839 hospitalized patients with hypertension at Yijishan Hospital of Wannan Medical College from July 2021 to April 2023 were collected, and the distribution frequency of each gene locus were analyzed. RESULTS: The genotype frequencies of ACE (I/D) I/I, I/D, and D/D were 42.1%, 46.0%, and 11.9%, respectively. the genotype frequencies of ADRB1 (1165G>C) G/G, G/C, and C/C were 8.3%, 40.0%, and 51.6%, respectively. The genotype frequencies of AGTR1 (1166A>C) A/A, A/C, and C/C were 90.2%, 9.8%, and 0.0%. The genotype frequencies of CYP2C9*3 (1075A>C) *1/*1, *1/*3, and *3/*3 were 91.3%, 8.7%, and 0.0%, respectively; the genotype frequencies of CYP2D6* 10 (100C > T) *1/*1, *1/*10, and *10/*10 were 25.0%, 36.6%, and 38.4%, respectively. The genotype frequencies of CYP3A5*3 (6986A>G) *1/*1, *1/*3, and *3/*3 were 7.0%, 39.0%, and 54.0%, respectively. The frequencies of NPPA (2238T>C) T/T, T / C, and C / C genotypes were 97.9%, 2.1%, and 0.0%, respectively. In addition, there was a significant difference in the genotype distribution frequency of multiple drug related gene loci in southern Anhui compared to other regions in China (P< 0.05). CONCLUSION: The genotype distribution frequency of hypertensive drug related gene loci had certain bias in southern Anhui, and were significant different from other regions in China, indicating that conducting genetic polymorphism testing of hypertensive drugs had certain guiding significance for the individualized application of hypertensive drugs in southern Anhui.

The mediating effect of mother-infant attachment on the relationship between maternal body image during pregnancy and postpartum depression / 中国实用护理杂志

Objective:To investigate the current status of maternal body image during pregnancy, mother-infant attachment and postpartum depression and explore the mediating effect of mother-infant attachment on maternal body image during pregnancy and postpartum depression, in order to effectively reduce the incidence of postpartum depression and provide reference and guidance for alleviating depressive symptoms.Methods:A total of 362 pregnant women admitted to obstetric wards in Women′s Hospital of Nanjing Medical University were selected for a cross-sectional investigation by applying the Edinburgh Postnatal Depression Scale, the Body Image in Pregnancy Scale and the Maternal Postnatal Attachment Scale by convenient sampling from July to September 2022. Model 4 in the SPSS macro program PROCESS was used to test the mediating effect of maternal infant attachment between body image and postpartum depression.Results:Totally 362 valid questionnaires were retrieved including 194 individuals aged ≤30 years old and 168 individuals aged >30 years old. The scores of maternal body image during pregnancy, mother-infant attachment and postpartum depression were (89.24 ± 15.56), (71.40 ± 8.05), 7.50 (4.00, 11.00) points.Conclusions:Body image during pregnancy can not only directly predict postpartum depression, but also indirectly predict postpartum depression through the mediating effect of mother-infant attachment. In order to prevent or reduce the occurrence of postpartum depression, nursing staff should carry out intervention research based on influencing the path of postpartum depression from the perspective of positive psychology.

Advances of peptide-centric data-independent acquisition analysis algorithms and software tools / 生物工程学报

Data-independent acquisition (DIA) is a high-throughput, unbiased mass spectrometry data acquisition method which has good quantitative reproducibility and is friendly to low-abundance proteins. It becomes the preferred choice for clinical proteomic studies especially for large cohort studies in recent years. The mass-spectrometry (MS)/MS spectra generated by DIA is usually heavily mixed with fragment ion information of multiple peptides, which makes the protein identification and quantification more difficult. Currently, DIA data analysis methods fall into two main categories, namely peptide-centric and spectrum-centric. The peptide-centric strategy is more sensitive for identification and more accurate for quantification. Thus, it has become the mainstream strategy for DIA data analysis, which includes four key steps: building a spectral library, extracting ion chromatogram, feature scoring and statistical quality control. This work reviews the peptide-centric DIA data analysis procedure, introduces the corresponding algorithms and software tools, and summarizes the improvements for the existing algorithms. Finally, the future development directions are discussed.

Construction of "lock-key" biological living material based on double engineered bacteria and its application on intestinal retention in vivo / 生物工程学报

At present, the research of biological living materials mainly focuses on applications in vitro, such as using a single bacterial strain to produce biofilm and water plastics. However, due to the small volume of a single strain, it is easy to escape when used in vivo, resulting in poor retention. In order to solve this problem, this study used the surface display system (Neae) of Escherichia coli to display SpyTag and SpyCatcher on the surface of two strains, respectively, and constructed a double bacteria "lock-key" type biological living material production system. Through this force, the two strains are cross-linked in situ to form a grid-like aggregate, which can stay in the intestinal tract for a longer time. The in vitro experiment results showed that the two strains would deposit after mixing for several minutes. In addition, confocal imaging and microfluidic platform results further proved the adhesion effect of the dual bacteria system in the flow state. Finally, in order to verify the feasibility of the dual bacteria system in vivo, mice were orally administrated by bacteria A (p15A-Neae-SpyTag/sfGFP) and bacteria B (p15A-Neae-SpyCatcher/mCherry) for three consecutive days, and then intestinal tissues were collected for frozen section staining. The in vivo results showed that the two bacteria system could be more detained in the intestinal tract of mice compared with the non-combined strains, which laid a foundation for further application of biological living materials in vivo.

Regulation of the TGF-β type I Receptor/Smad Pathway Inhibits Renal Fibrosis by Shenkang Injection / 世界科学技术-中医药现代化

Objective Chinese herbal injections called Shenkang injections(SKI)have become widely used for treating chronic kidney disease in the clinic.An investigation into the underlying mechanisms of SKI inhibition of renal tubular epithelial cell trans differentiation treated with TGF-β1 was carried out in this study.Methods To create an in vitro model of RF,HK-2 cells were treated with TGF-1(10 ng·mL-1)at 37℃for 48 h.After the cells were treated with SKI for 48 h,the morphology of the cells was observed by electron microscope.And Western blot,RT-PCR and immunofluorescence techniques were used to detect α-Smooth muscle actin(α-SMA),type III collagen(COI-Ⅲ),TGF-β1,Smad3,Smad7 and TβR-I expression changes of proteins and genes.Results SKI can significantly reduce expressed proteins and genes related to renal fibrosis,such as α-Smooth muscle actin(α-SMA)and type Ⅲ collagen(COI-Ⅲ).SKI control the production of proteins associated with the TGF-β/Smad signaling pathway.By downregulating TGF-β1,Smad3,and TβR-I protein expression,as well as upregulating Smad7 protein expression,it is able to prevent cell trans differentiation.Conclusions SKI can inhibit renal tubular epithelial cell mesenchymal trans differentiation.In addition,this drug may prevent chronic kidney disease by downregulating the expression of TβR-I and regulating the TGF-β/Smad pathway-related molecules.

Difference analysis of chemical components in roots and rhizomes of 3 medicinal plants of Gentiana from the same origin / 中国药房

OBJECTIVE To provide reference for exploring alternative resources of Gentiana rigescens from the plants of Gentiana. METHODS The contents of four components （gentiopicroside， swertiamarin， swertioside and amarogentin） in the roots and rhizomes from 3 plants of Gentiana （G. rigescens， G. cephalantha， G. delavayi） were determined by high-performance liquid chromatography （HPLC）. The chemical compositions in the above roots and rhizomes were identified by ultra-performance liquid chromatography electrospray ionization quarter-time of flight mass spectrometry （UPLC-ESI-Q-TOF-MS）， and the differences were analyzed by principal component analysis （PCA）. RESULTS Four active components such as gentiopicroside， swertiamarin， swertioside and amarogentin were detected in the roots and rhizomes of G. rigescens and G. cephalantha， and the contents of the four components were similar in both. The contents of gentiopicroside in the root and rhizome of G. cephalantha and G.rigescens were more than four times of the limit standard of the Chinese Pharmacopoeia （Part Ⅰ） in 2020； However， only swertiamarin， swertioside and amarogentin were detected in the roots and rhizomes of G.delavayi， and the contents of swertioside and amarogentin were 34.12 and 8.81 times of those of G. rigescens， respectively. In addition， a total of 33 compounds 术。E-mail：515227235@qq.com were identified from the roots and rhizomes of 3 plants of Gentiana by UPLC-ESI-Q-TOF-MS， mainly iridoids. Additionally， G. rigescens and G. cephalantha contained xantones， G. delavayi contained flavonoids. PCA showed that there was a small difference between G. rigescens and G. cephalantha； however， there was a big difference between G. delavayi and G. rigescens. CONCLUSIONS The difference between the roots and rhizomes of G. cephalantha and G. rigescens from the same origin is small and there is substitutability； while the difference in the chemical components from roots and rhizomes between G. delavayi and G. rigescens is great and G. delavayi cannot be used as medicine instead of G. rigescens.

Clinical Application Advances of Antipsychotic Drugs in Female Schizophrenic Patients / 医药导报

Female patients with schizophrenia exhibit a slower rate of absorption and excretion,leading to higher blood levels of antipsychotic drugs in their bodies and consequently causing more drug side effects.Women also have different levels of estrogen at different stages of life,and estrogen improves the efficacy of antipsychotic drugs by increasing dopamine D2receptor sensitivity.It is necessary to adjust the dosage of antipsychotic medication based on the level of estrogen,while also monitoring indicators such as blood glucose,triglycerides,cholesterol,and prolactin to minimize medication side effects.Nevertheless,the current literatures do not provide specific treatment plans for schizophrenia tailored to different genders,which is not the optimal treatment strategy for female patients.This review aims to summarize and categorize the differences in prescription,pharmacokinetics,pharmacodynamics,efficacy,and side effects in female patients with schizophrenia,and to provide scientific recommendations for drug treatment strategies in different stages of a woman's life(premenopausal,pregnancy,lactation,postmenopausal).