Potential mechanisms of ZiGongDing in treating HPV-induced cervical intraepithelial neoplasia: a network pharmacology and experimental verification study.

The onset of cervical intraepithelial neoplasia (CIN) is strongly associated with persistent infection caused by high-risk human papillomavirus (HPV). ZiGongDing (ZGD), a traditional Chinese medicine, has progressed to clinical application in HPV-induced CIN treatment, yet the underlying mechanism remains unclear. The objective of this paper is to explore the mechanism of ZGD in treating HPV-induced CIN by integrating a combination of network pharmacology and experimental validation. The active ingredients and targets of ZGD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. CIN-related targets were sourced from GeneCards and the Online Mendelian Inheritance in Man (OMIM) database. Protein-protein interaction (PPI) and functional enrichment analyses were conducted to determine the potential molecular mechanism. The herb-active ingredient-target network was constructed by Cytoscape software. To further validate the therapeutic mechanism, molecular docking and in vitro experiments were performed. In this study, we identified 60 active ingredients in ZGD and 46 common targets in of CIN treatment. The PPI network analysis revealed estrogen receptor 1 (ESR1) as a pivotal target in ZGD against CIN. Functional enrichment analysis showed that the estrogen signaling pathway was mostly enriched, and ESR1 was involved. The herb-active ingredient-target network and relative literature identified cnidimol B as the primary active ingredient. Molecular docking demonstrated a strong binding affinity between ESR1 and cnidimol B. Cellular experiments revealed that cnidimol B could significantly decrease the viability of HeLa and CaSki cells. Moreover, the expression of ESR1 was notably upregulated in HeLa and CaSki cells after treatment with cnidimol B. Our study proposes a novel mechanism underlying ZGD against CIN, which involves the modulation of ESR1. This insight lays a solid foundation for further exploring and optimizing ZGD's therapeutic potential.

Development and validation of a nomogram to predict poor efficacy of imatinib in the treatment of newly diagnosed chronic phase chronic myeloid leukemia patients.

Background: Imatinib is the most widely used tyrosine kinase inhibitor (TKI) in patients with newly diagnosed chronic-phase chronic myeloid leukemia(CML-CP). However, failure to achieve optimal response after imatinib administration, and subsequent switch to second-generation TKI therapy results in poor efficacy and induces drug resistance. In the present study, we developed and validated a nomogram to predict the efficacy of imatinib in the treatment of patients newly diagnosed with CML-CP in order to help clinicians truly select patients who need 2nd generation TKI during initial therapy and to supplement the risk score system. Methods: We retrospectively analyzed 156 patients newly diagnosed with CML-CP who met the inclusion criteria and were treated with imatinib at the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2012 to June 2022. The patients were divided into a poor-response cohort (N = 60)and an optimal-response cohort (N = 43) based on whether they achieved major molecular remission (MMR) after 12 months of imatinib treatment. Using univariate and multivariate logistic regression analyses, we developed a chronic myeloid leukemia imatinib-poor treatment (CML-IMP) prognostic model using a nomogram considering characteristics like age, sex, HBG, splenic size, and ALP. The CML-IMP model was internally validated and compared with Sokal, Euro, EUTOS, and ELTS scores. Results: The area under the curve of the receiver operator characteristic curve (AUC)of 0.851 (95% CI 0.778-0.925) indicated satisfactory discriminatory ability of the nomogram. The calibration plot shows good consistency between the predicted and actual observations. The net reclassification index (NRI), continuous NRI value, and the integrated discrimination improvement (IDI) showed that the nomogram exhibited superior predictive performance compared to the Sokal, EUTOS, Euro, and ELTS scores (P < 0.05). In addition, the clinical decision curve analysis (DCA) showed that the nomogram was useful for clinical decision-making. In predicting treatment response, only Sokal and CML-IMP risk stratification can effectively predict the cumulative acquisition rates of CCyR, MMR, and DMR (P<0.05). Conclusion: We constructed a nomogram that can be effectively used to predict the efficacy of imatinib in patients with newly diagnosed CML-CP based on a single center, 10-year retrospective cohort study.

Chronic myeloid leukemia with two rare fusion gene transcripts of atypical BCR::ABL: A case report and literature review.

RATIONALE: Imatinib is a standard treatment for Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML), but its efficacy in rare BCR::ABL variants is underexplored. PATIENT CONCERNS: A 67-year-old woman was admitted to the Second Affiliated Hospital of Xi'an Jiaotong University in March 2022 due to elevated white blood cells. DIAGNOSIS: Karyotype analysis revealed clonal abnormalities involving the variant t(9;22) and positive results for atypical BCR::ABL variants (e14a3 and e13a3). The clinical diagnosis was CML, chronic phase, Ph+, with rare BCR::ABL-e13a3- and BCR::ABL-e14a3-positive findings. INTERVENTION: The patient was administered daily imatinib mesylate (400 mg). OUTCOMES: After 4 weeks, a swift molecular response was observed: BCR::ABL-e13a3 transcript level at 2.82 × 10-1 (28.24%), and BCR::ABL-e14a3 transcript level at 4.68 × 10-1 (46.76%). Within 3 months, a complete cytogenetic response was achieved, with a Ph chromosome ratio of 0. Early molecular response was evident as BCR::ABL-e13a3 transcript level reached 5.11 × 10-3 (0.51%), and BCR::ABL-e14a3 transcript level at 6.26 × 10-3 (0.63%). The imatinib mesylate treatment continued without significant toxicity. LESSONS: This case emphasizes the potential effectiveness of imatinib mesylate in managing rare BCR::ABL fusion gene variants of CML. Screening for these atypical variants is advised for suspected CML patients who test negative for common BCR::ABL fusion gene variants. The presented case underscores the positive outcomes achieved with imatinib treatment for a patient with rare BCR::ABL variants, contributing valuable insights for the management of similar cases. Screening for unusual fusion gene variants should be a consideration in CML diagnosis for comprehensive treatment strategies.

Efficacy of recombinant human interleukin-11 in preventing and treating oral mucositis after chemotherapy for patients with acute leukemia.

OBJECTIVE: This study aimed to investigate the clinical effects of recombinant human interleukin-11 (rhIL-11) gargle on preventing and treating oral mucositis (OM) after chemotherapy for acute leukemia. METHODS: This single-site, prospective, observer-blinded, nonrandomized controlled trial was conducted on 74 patients with acute leukemia, who were divided into the experimental and control groups. The patients in the experimental group were treated with IL-11 gargle, and those in the control group were treated with sodium bicarbonate gargle. We examined the time and severity of oral mucositis, severity and duration of associated pain, healing time of mucositis, effects of OM on eating, and levels of T-cell subset indicators before and after treatment to evaluate the effects of IL-11 treatment. RESULTS: The proportion of patients with severe OM was significantly lower in the experimental group than in the control group. Mucositis occurred later in the experimental group compared with the control group. The degree and duration of pain, ulcer healing time, and effects on eating were lower in the experimental group compared with the control group. Following treatment, the levels of all T-cell subset indicators improved in each of the two groups. However, the rate of improvement was significantly higher in the experimental group than in the control group. These differences were statistically significant (P < 0.05). CONCLUSIONS: IL-11 gargle reduced the severity of OM after chemotherapy for acute leukemia. Treatment with IL-11 relieved pain, promoted healing, and improved the curative effect of the condition, making it worthy of clinical promotion.

[Comparison of results of prenatal diagnosis by different techniques for fetuses with increased nuchal translucency].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness. METHODS: Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13+6 gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test. RESULTS: The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13+4 weeks (11+5 ~ 13+6 weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS. CONCLUSION: NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.

Clinical Features and Blood Indicators for Severity and Prognosis in COVID-19 Patients.

BACKGROUND: This study aimed to analyze the clinical manifestations and blood indicators to deepen the understanding of Coronavirus disease 2019 (COVID-19). METHODS: COVID-19 patients admitted to C10 West Ward, Tongji Hospital in Wuhan City ("West Ward") between January 31 and March 28, 2020, were retrospectively analyzed. RESULTS: A total of 61 COVID-19 patients were hospitalized, wherein the non-critical Group had 30 cases, while the critical group had 31 (including 14 survivors and 17 deaths). Age, the proportion of fever cases, white blood cell (WBC), basophils, red blood cell (RBC), hemoglobin, lactate dehydrogenase (LDH), C-reactive protein (CRP), high-sensitivity troponin, pro-BNP (brain natriuretic peptide), prothrombin time (PT), and D-dimer were higher in the critical group while lymphocytes, eosinophils, albumin were lower compared with those of the non-critical group (all p < 0.05). WBC (p = 0.008), basophils (p = 0.034), and LDH (p = 0.005) of the death subgroup climbed remarkably in comparison with those of the survival subgroup. CONCLUSIONS: Advanced age, high fever, increases in indicators such as WBC, basophils, CRP, LDH, high-sensitivity troponin, pro-BNP, and D-dimer, and decreases in indicators, including lymphocytes, eosinophils, and albumin, might forebode a critical condition.

Comprehensive Analysis of Novel Genes and Pathways Associated with Osteogenic Differentiation of Adipose Stem Cells.

Background: Adipose-derived stem cells (ADSCs) are an important alternative source of mesenchymal stem cells (MSCs) and show great promise in tissue engineering and regenerative medicine applications. However, identifying the novel genes and pathways and finding the underlying mechanisms regulating ADSCs osteogenic differentiation remain urgent. Methods: We downloaded the gene expression profiles of GSE63754 and GSE37329 from the Gene Expression Omnibus (GEO) Database. We derived differentially expressed genes (DEGs) before and after ADSC osteogenic differentiation, followed by Gene Ontology (GO) functional and KEGG pathway analysis and protein-protein interaction (PPI) network analysis. 211 differentially expressed genes (142 upregulated genes and 69 downregulated genes) were aberrantly expressed. GO analysis revealed that these DEGs were associated with extracellular matrix organization, protein extracellular matrix, and semaphorin receptor binding. Conclusions: Our study provides novel genes and pathways that play important roles in regulating ADSC osteogenic differentiation, which may have potential therapeutic targets for clinic.

A tRNA-derived fragment of ginseng protects heart against ischemia/reperfusion injury via targeting the lncRNA MIAT/VEGFA pathway.

Traditional Chinese medicines (TCMs) have been widely used for treating ischemic heart disease (IHD), and secondary metabolites are generally regarded as their pharmacologically active components. However, the effects of nucleic acids in TCMs remain unclear. We reported for the first time that a 22-mer double-strand RNA consisting of HC83 (a tRNA-derived fragment [tRF] from the 3' end of tRNAGln(UUG) of ginseng) and its complementary sequence significantly promoted H9c2 cell survival after hypoxia/reoxygenation (H/R) in vitro. HC83_mimic could also significantly improve cardiac function by maintaining both cytoskeleton integrity and mitochondrial function of cardiomyocytes. Further in vivo investigations revealed that HC83_mimic is more potent than metoprolol by >500-fold against myocardial ischemia/reperfusion (MI/R) injury. In-depth studies revealed that HC83 directly downregulated a lncRNA known as myocardial infarction-associated transcript (MIAT) that led to a subsequent upregulation of VEGFA expression. These findings provided the first evidence that TCM-derived tRFs can exert miRNA-like functions in mammalian systems, therefore supporting the idea that TCM-derived tRFs are promising RNA drug candidates shown to have extraordinarily potent effects. In summary, this study provides a novel strategy not only for discovering pharmacologically active tRFs from TCMs but also for efficiently exploring new therapeutic targets for various diseases.

Comprehensive Therapy for Infant Vascular Tumor Associated With Kasabach-Merritt Phenomenon-Single-Center Primary Experience.

Objective: To introduce our single-center experience of infant vascular tumor associated with Kasabach-Merritt phenomenon (KMP) which received combined medicine treatment with intralesional laser photocoagulation (ILP) and sclerotherapy. Methods: A retrospective study was conducted using medical records of all children with a diagnosis of kaposiform hemangioendothelioma (KHE) or tufted angioma (TA) associated with KMP treated with medicine, intralesional laser photocoagulation (ILP), and sclerotherapy between February 2017 and November 2020. Clinical features, response to comprehensive therapy, and outcomes were recorded. Results: A total of 23 patients including nine females (39%) and 14 males (61%) were identified. The mean age was 6.9 months (age range, 11 days-2 years) at the time of treatment. Nine children (39%) demonstrated sensitivity to single corticosteroid therapy; 14 children (61%) received combined therapy with intravenous Vincristine (VCR) and corticosteroid therapy. All children had at least two ILP and sclerotherapy performed, with a mean of 3.5 procedures (range: 2-6). Of these 14 children, only one experienced a relapse of thrombocytopenia and the remaining 13 children had no clinical symptoms recurred. Conclusion: The combined therapy modalities could induce a more rapid tumor response and resolution of KMP and decrease the rebound rates. This research presents a novel and safe multi-modality treatment for infant vascular tumors associated with KMP.

Analysis of influencing factors of community-acquired pneumonia with deep venous thrombosis in elderly communities.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the common infectious diseases that threaten human health, venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE), is a global health care problem. Acute infection and age ≥70 years are important risk factors for VTE in internal medicine inpatients. There is increasing evidence that acute infectious diseases caused by bacterial and viral infections can induce coagulation, platelet (PLT) activation and inhibit the activity of anticoagulant factors. However, there is no consensus on whether patients with CAP suffer from DVT. Finding out the clinical characteristics and risk factors of DVT in elderly patients with CAP is helpful for early identification of high-risk patients with VTE and timely prevention, which can significantly reduce the occurrence of VTE in hospitals. METHODS: Data was collected from 505 patients with CAP aged ≥70 years old hospitalized in the Department of Respiratory and Critical Care Medicine. 133 patients with DVT were selected as the DVT group. DVT score and risk grading were performed for all patients using Padua. Fifty-seven cases were diagnosed as having severe pneumonia, including 50 cases diagnosed as having septic shock. Padua, D-dimer, between the DVT group and the control group, the severe pneumonia group and the non-severe pneumonia group, and the severe pneumonia DVT group and the control group were compared. RESULTS: (I) The incidence of DVT with severe pneumonia was much higher than with non-severe pneumonia (P<0.001). The incidence of DVT in patients with septic shock and non-septic shock was 74.0% (37/50) and 28.6% (2/7) respectively (P=0.0154). (II) There were significant differences in Padua scores between the DVT group and the control group and between the severe pneumonia group and non-severe pneumonia group (P<0.001). (III) There were significant differences in D-dimer level between the DVT group and the control group and between the severe pneumonia group and the non-severe pneumonia group (P<0.001). (IV) Regression analysis indicated the central venous catheter (CVC), D-dimer value, and Padua score were significantly correlated with thrombosis (P=0.042, <0.001, 0.043). CONCLUSIONS: Severe pneumonia in elderly patients and septic shock may be complicated by DVT, and central venous catheterization and D-dimer are closely related to thrombosis.

Expression of Serum PSA, Nesfatin-1, and AMH in Patients with Polycystic Ovary Syndrome.

Insulin resistance and hyperandrogenism are the leading causes of polycystic ovary syndrome (PCOS). Therefore, it has great significance to study the expression levels of PSA, nesfatin-1, and AMH. To provide some reference for clinical diagnosis and treatment of polycystic ovary syndrome (PCOS), the expression levels of PSA, nesfatin-1, and AMH in serum of patients with polycystic ovary syndrome (PCOS) were investigated. The experimental group consisted of 200 patients with polycystic ovary syndrome treated in Shanghai Huashan Hospital from July 2018 to July 2019. The control group consisted of 150 healthy women without pregnancy. The PSA, nesfatin-1, and AMH levels in serum were detected by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). The serum levels of prostate-specific antigen (PSA) and anti-Mullerian hormone (AMH) were 16.53 ± 0.67pg/ml and 10.75 ± 4.02pg/ml in the experimental group (PCOS patients), which were significantly higher than those in the control group (3.27 ± 0.43pg/ml and 5.18 ± 1.84pg/ml, respectively), while the inhibitive factors in the experimental group (1.89 ± 0.99mg/ml) were significantly higher than those in the control group (1.10 ± 0.97mg/ml). There was no significant difference in nesfatin-1. The levels of PSA and nesfatin-1, nesfatin-1, and AMH and the levels of PSA and AMH in patients with polycystic ovary syndrome were positively correlated, and the differences were statistically significant. The levels of PSA, nesfatin-1, and AMH in patients with polycystic ovary syndrome of different ages were different, and the differences were significant and negatively correlated with the age increasing. PSA, nesfatin-1, and AMH levels in patients with polycystic ovary syndrome were significantly different from those in control nonpregnant women. There was a certain correlation between the levels of PSA, nesfatin-1, and AMH, and age. The results have specific clinical reference significance for the diagnosis and treatment of patients with polycystic ovary syndrome.

Effect of Drought Stress on Degradation and Remodeling of Membrane Lipids in Nostoc flagelliforme.

Nostoc flagelliforme is a kind of terrestrial edible cyanobacteria with important ecological and economic value which has developed special mechanisms to adapt to drought conditions. However, the specific mechanism of lipidome changes in drought tolerance of N. flagelliforme has not been well understood. In this study, the ultra-high-performance liquid chromatography and mass spectrometry were employed to analyze the lipidome changes of N. flagelliforme under dehydration. A total of 853 lipid molecules were identified, of which 171 were significantly different from that of the control group. The digalactosyldiacylglycerol/monogalactosyldiacylglycerol (DGDG/MGDG) ratio was increased. The amount of wax ester (WE) was sharply decreased during drought stress, while Co (Q10) was accumulated. The levels of odd chain fatty acids (OCFAs) were increased under dehydration, positively responding to drought stress according to the energy metabolism state. In conclusion, the lipidomic data corroborated that oxidation, degradation, and biosynthesis of membrane lipids took place during lipid metabolism, which can respond to drought stress through the transformation of energy and substances. Besides, we constructed a lipid metabolic model demonstrating the regulatory mechanism of drought stress in N. flagelliforme. The present study provides insight into the defense strategies of cyanobacteria in lipid metabolic pathways.

Proteome profiling reveals changes in energy metabolism, transport and antioxidation during drought stress in Nostoc flagelliforme.

BACKGROUND: Drought is an important abiotic stress that constrains the growth of many species. Despite extensive study in model organisms, the underlying mechanisms of drought tolerance in Nostoc flagelliforme remain elusive. RESULTS: We characterized the drought adaptation of N. flagelliforme by a combination of proteomics and qRT-PCR. A total of 351 differentially expressed proteins involved in drought stress adaptation were identified. It was found that the expression of several nutrient influx transporters was increased, including molybdate ABC transporter substrate binding protein (modA), sulfate ABC transporter substrate-binding protein (sbp) and nitrate ABC transporter (ntrB), while that of efflux transporters for toxic substances was also increased, including arsenic transporting ATPase (ArsA), potassium transporter (TrkA) and iron ABC transporter substrate-binding protein (VacB). Additionally, photosynthetic components were reduced while sugars built up during drought stress. Non-enzymatic antioxidants, orange carotenoid protein (OCP) homologs, cytochrome P450 (CYP450), proline (Pro) and ascorbic acid (AsA) were all altered during drought stress and may play important roles in scavenging reactive oxygen species (ROS). CONCLUSION: In this study, N. flagelliforme may regulates its adaptation to drought stress through the changes of protein expression in photosynthesis, energy metabolism, transport, protein synthesis and degradation and antioxidation. HIGHLIGHTS: • A total of 351 DEPs involved in adaptation to drought stress were identified. • Changes in the expression of six OCP homologs were found in response to drought stress. • Differential expression of transporters played an important role in drought stress adaptation. • Most PSII proteins were downregulated, while PSI proteins were unchanged in response to drought stress. • Sugar metabolism was upregulated in response to drought stress.

CD73+ adipose-derived stem cells reduce scar formation through PLOD1.

Background: Reducing cutaneous scar formation is important for assessing the success of skin wound healing. Although it is generally accepted that adipose-derived mesenchymal stem cells (AMSCs) have substantial therapeutic potential, efforts are continuously made to improve the outcome of AMSC therapy. Post-transcriptional suppression of procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) in AMSCs has been shown to greatly reduce scar formation during skin wound healing, likely through modulating macrophage polarization. In the present study, we tested whether a CD73+ subpopulation of AMSCs could reduce scar formation compared with CD73- AMSCs. Methods: The gene profile of CD73+ versus CD73- AMSCs was obtained from a validated public database, GSE167219. AMSCs were isolated from adipose tissue surrounding the groin of mice, after which CD73+ versus CD73- AMSCs were sorted using flow cytometry. PLOD1 levels were determined in CD73+ versus CD73- AMSCs. Then, PLOD1 in CD73- AMSCs was depleted by a short-hair interfering RNA against PLOD1 (sh-PLOD1), while PLOD1 in CD73+ AMSCs was increased by expression of a PLOD1 transgene. A blade was used to induce a skin injury on the middle back of the mice. Either CD73+ AMSCs or CD73+ PLOD1 AMSCs or CD73- AMSCs or CD73- sh-PLOD1 AMSCs were intravenously transplanted into the injured region of the mice. Fibrosis and the underlying mechanisms were investigated. Co-immunoprecipitation was performed to evaluate interaction between CD73 and PLOD1. Results: CD73+ AMSCs expressed significantly lower levels of PLOD1, a potent stimulator of fibrosis, compared with CD73- AMSCs. Transplantation of CD73+ AMSCs generated significantly reduced fibrosis at the skin injury site compared with CD73- AMSCs. However, expression of PLOD1 in CD73+ AMSCs abolished its advantageous effects on fibrosis reduction, while depletion of PLOD1 in CD73- AMSCs improved the outcome of fibrosis to the levels of transplantation of CD73+ AMSCs. Co-immunoprecipitation showed no direct protein interaction between CD73 and PLOD1. Conclusions: CD73+ AMSCs are a subgroup of AMSCs with better therapeutic effects on wound healing, and can inhibit scar formation through reduced PLOD1 in an indirect manner.

Improving the Performance of Perovskite Solar Cells with Insulating Additive-Modified Hole Transport Layers.

Invert perovskite solar cells (PSCs) present a great potential for next-generation photovoltaics for their flexibility and tandem adaptability. In order to improve the conductivity of the hole transport layer (HTL), such as poly(triarylamine), highly conductive additives (e.g., F4TCNQ, Li-TFSI) were generally applied to achieve a power conversion efficiency (PCE) exceeding 21%. However, these additives significantly affect the long-term stability of the devices due to their humidity sensitivity. In this work, the HTL was counterintuitively optimized with insulating additives, such as polyphenylene sulfide, which enhanced PCE from 19.1 to 21.5% along with a noticeable improvement in device stability with T50 of 574 h under double 85 aging conditions. The performance enhancement is attributed to larger grain sizes in perovskite films on the HTL and better energy-level alignment between the HTL and perovskite after introducing the insulating additives, which compensate negative influence caused by additive-induced reduction in conductivity. Our work demonstrates that low-conductivity additives, rather than the commonly used high-conductivity counterparts, can also contribute to improving the photovoltaic performance in PSCs.

Carbon Metabolism and the ROS Scavenging System Participate in Nostoc flagelliforme's Adaptive Response to Dehydration Conditions through Protein Acetylation.

Acetylation represents an extensively occurring protein post-translational modification (PTM) that plays a key role in many cellular physiological and biochemical processes. However, studies on PTMs such as acetylation of lysine (LysAc) in cyanobacteria are still rare. In this study, a quantitative LysAc approach (acetylome) on the strains of Nostoc flagelliforme subjected to different dehydration treatments was conducted. We observed that starch contents were significantly accumulated due to dehydration treatments, and we identified 2474 acetylpeptides and 1060 acetylproteins based on acetylome analysis. Furthermore, an integrative analysis was performed on acetylome and nontargeted metabolism, and the results showed that many KEGG terms were overlapped for both omics analyses, including starch and sucrose metabolism, transporter activity, and carbon metabolism. In addition, time series clustering was analyzed, and some proteins related to carbon metabolism and the ROS scavenging system were significantly enriched in the list of differentially abundant acetylproteins (DAAPs). These protein expression levels were further tested by qPCR. A working model was finally proposed to show the biological roles of protein acetylation from carbon metabolism and the ROS scavenging system in response to dehydration in N. flagelliforme. We highlighted that LysAc was essential for the regulation of key metabolic enzymes in the dehydration stress response.

Comprehensive Phosphoproteomic Analysis of Nostoc flagelliforme in Response to Dehydration Provides Insights into Plant ROS Signaling Transduction.

Terrestrial cyanobacteria, originated from aquatic cyanobacteria, exhibit a unique mechanism for drought adaptation during long-term evolution. To elucidate this diverse adaptive mechanism exhibited by terrestrial cyanobacteria from the post-translation modification aspect, we performed a global phosphoproteome analysis on the abundance of phosphoproteins in response to dehydration using Nostoc flagelliforme, a kind of terrestrial cyanobacteria having strong ecological adaptability to xeric environments. A total of 329 phosphopeptides from 271 phosphoproteins with 1168 phosphorylation sites were identified. Among these, 76 differentially expressed phosphorylated proteins (DEPPs) were identified for each dehydration treatment (30, 75, and 100% water loss), compared to control. The identified DEPPs were functionally categorized to be mainly involved in a two-component signaling pathway, photosynthesis, energy and carbohydrate metabolism, and an antioxidant system. We concluded that protein phosphorylation modifications related to the reactive oxygen species (ROS) signaling pathway might play an important role in coordinating enzyme activity involved in the antioxidant system in N. flagelliforme to adapt to dehydration stress. This study provides deep insights into the extensive modification of phosphorylation in terrestrial cyanobacteria using a phosphoproteomic approach, which may help to better understand the role of protein phosphorylation in key cellular mechanisms in terrestrial cyanobacteria in response to dehydration.

Increased levels of ferritin on admission predicts intensive care unit mortality in patients with COVID-19.

BACKGROUND: The aim of this study was to evaluate hyperferritinemia could be a predicting factor of mortality in hospitalized patients with coronavirus disease-2019 (COVID-19). METHODS: A total of 100 hospitalized patients with COVID-19 in intensive care unit (ICU) were enrolled and classified into moderate (n = 17), severe (n = 40) and critical groups (n = 43). Clinical information and laboratory results were collected and the concentrations of ferritin were compared among different groups. The association between ferritin and mortality was evaluated by logistic regression analysis. Moreover, the efficiency of the predicting value was assessed using receiver operating characteristic (ROC) curve. RESULTS: The amount of ferritin was significantly higher in critical group compared with moderate and severe groups. The median of ferritin concentration was about three times higher in death group than survival group (1722.25 µg/L vs. 501.90 µg/L, p < 0.01). The concentration of ferritin was positively correlated with other inflammatory cytokines, such as interleukin (IL)-8, IL-10, C-reactive protein (CRP) and tumor necrosis factor (TNF)-α. Logistic regression analysis demonstrated that ferritin was an independent predictor of in-hospital mortality. Especially, high-ferritin group was associated with higher incidence of mortality, with adjusted odds ratio of 104.97 [95% confidence interval (CI) 2.63-4185.89; p = 0.013]. Moreover, ferritin had an advantage of discriminative capacity with the area under ROC (AUC) of 0.822 (95% CI 0.737-0.907) higher than procalcitonin and CRP. CONCLUSION: The ferritin measured at admission may serve as an independent factor for predicting in-hospital mortality in patients with COVID-19 in ICU.

ANTECEDENTES: El objetivo de este estudio fue evaluar si la hiperferritinemia podría ser un factor predictivo de la mortalidad en pacientes hospitalizados con enfermedad por coronavirus de 2019 (COVID-19). MÉTODOS: Se incluyó un total de 100 pacientes hospitalizados con COVID-19 en la unidad de cuidados intensivos (UCI), clasificándose como grupos moderado (n = 17), grave (n = 40) y crítico (n = 43). Se recopiló la información clínica y de laboratorio, comparándose los niveles de ferritina entre los diferentes grupos. Se evaluó la asociación entre ferritina y mortalidad mediante un análisis de regresión logística. Además, se evaluó la eficacia del valor predictivo utilizando la curva ROC (receiver operating characteristic). RESULTADOS: La cantidad de ferritina fue significativamente superior en el grupo de pacientes críticos en comparación con el grupo de pacientes graves. La media de concentración de ferritina fue cerca de 3 veces superior en el grupo de muerte que en el grupo de supervivientes (1.722,25 µg/L vs. 501,90 µg/L, p < 0,01). La concentración de ferritina guardó una correlación positiva con otras citoquinas inflamatorias tales como interleucina (IL)-8, IL-10, proteína C reactiva (PRC) y factor de necrosis tumoral (TNF)-α. El análisis de regresión logística demostró que la ferritina era un factor predictivo independiente de la mortalidad intrahospitalaria. En especial, el grupo de ferritina alta estuvo asociado a una mayor incidencia de la mortalidad, con un valor de odds ratio ajustado de 104,97 [intervalo de confianza (IC) del 95% 2,63-4.185,89; p = 0,013]. Además, el valor de ferritina tuvo una ventaja de capacidad discriminativa en el área bajo la curva ROC (AUC) de 0,822 (IC 95% 0,737-0,907] superior al de procalcitonina y PRC. CONCLUSIÓN: El valor de ferritina medido durante el ingreso puede servir de factor independiente para prevenir la mortalidad intrahospitalaria en los pacientes de COVID-19 en la UCI.

First 40Ar/39Ar analyses of Australasian tektites in close association with bifacially worked artifacts at Nalai site in Bose Basin, South China: The question of the early Chinese Acheulean.

The recently discovered Nalai site is one of the Bose Basin localities, which is key to studying the earliest bifaces in China. The Nalai site has yielded an abundance of lithic artifacts, including bifaces and tektites in close association. The total fusion 40Ar/39Ar method was applied to four tektites discovered beside and contemporaneous with bifaces in the red laterite sediments of the upper levels of the T4 terrace (layers 4 and 5). Our 40Ar/39Ar data with a weighted mean age of 809 ± 12 ka provide for the first time unequivocal dates for bifacial production at Bose, broadly consistent with the precise Australasian tektite age of 788.1 ± 2.8 ka, recently published by other investigators. The relatively important errors reported here suggest sample contamination by clasts or bubbles for the oldest aliquots and alteration for the younger ones. The lithic assemblage from layers 4 and 5 of the Nalai site is quite similar to that found at other sites in the Bose Basin. The assemblages are dominated by choppers, but bifaces, picks, and unifaces give a Mode 2 and Acheulean-type character to the series. The high frequency of the round tongue-shaped tip, a low elongation index, and a wide and thick base characterize the Large Cutting Tools. These results contribute to resolving ongoing debates on the timing and origin of bifaces and the Acheulean in China.

Global analysis of protein succinylation modification of Nostoc flagelliforme in response to dehydration.

Nostoc flagelliforme is a type of terrestrial cyanobacteria that is distributed in arid or semi-arid steppes in China. To research the molecular mechanisms underlying the adaptation of N. flagelliforme to drought stress, the succinylated expression profile and changes in N. flagelliforme that resulted as a response to dehydration were analyzed by label-free proteomics. A total of 1149 succinylated sites, 1128 succinylated peptides, and 396 succinylated proteins were identified. Succinylated proteins were differentially involved in photosynthesis and energy metabolism, as well as in reactive oxygen species (ROS) scavenging. Motif-X analysis of succinylated sites determined a succinylation motif [KxxG]. N. flagelliforme adapts to dehydration by increasing glucose metabolism and pentose phosphate pathway flux, and decreasing photosynthetic rate, which some of the key proteins were succinylated. ROS scavenging was mainly involved in the regulation of the enzyme antioxidant defense system and non-enzymatic antioxidant defense system through succinylation modification, thus eliminating excessive ROS. Protein succinylation of N. flagelliforme may play an important regulatory role in response to dehydration. The results are foundational, as they can inform future research into the mechanisms involved in the succinylation regulation mechanism of N. flagelliforme in response to dehydration. SIGNIFICANCE: The global succinylation network involved in response to dehydration in N. flagelliforme has been established. We found that many succinylated proteins were involved in photosynthesis, glucose metabolism and antioxidation. The global survey of succinylated proteins and the changes of succinylated levels in response to dehydration provided effective information for the drought tolerance mechanism in N. flagelliforme.