The haplotype-resolved genome of diploid Chrysanthemum indicum unveils new acacetin synthases genes and their evolutionary history.

Acacetin, a flavonoid compound, possesses a wide range of pharmacological effects, including antimicrobial, immune regulation, and anticancer effects. Some key steps in its biosynthetic pathway were largely unknown in flowering plants. Here, we present the first haplotype-resolved genome of Chrysanthemum indicum, whose dried flowers contain abundant flavonoids and have been utilized as traditional Chinese medicine. Various phylogenetic analyses revealed almost equal proportion of three tree topologies among three Chrysanthemum species (C. indicum, C. nankingense, and C. lavandulifolium), indicating that frequent gene flow among Chrysanthemum species or incomplete lineage sorting due to rapid speciation might contribute to conflict topologies. The expanded gene families in C. indicum were associated with oxidative functions. Through comprehensive candidate gene screening, we identified five flavonoid O-methyltransferase (FOMT) candidates, which were highly expressed in flowers and whose expressional levels were significantly correlated with the content of acacetin. Further experiments validated two FOMTs (CI02A009970 and CI03A006662) were capable of catalyzing the conversion of apigenin into acacetin, and these two genes are possibly responsible acacetin accumulation in disc florets and young leaves, respectively. Furthermore, combined analyses of ancestral chromosome reconstruction and phylogenetic trees revealed the distinct evolutionary fates of the two validated FOMT genes. Our study provides new insights into the biosynthetic pathway of flavonoid compounds in the Asteraceae family and offers a model for tracing the origin and evolutionary routes of single genes. These findings will facilitate in vitro biosynthetic production of flavonoid compounds through cellular and metabolic engineering and expedite molecular breeding of C. indicum cultivars.

Left Hepatectomy Combined with Right Hepatic Artery Resection and Reconstruction for Hilar Cholangiocarcinoma.

BACKGROUND: Hepatectomy combined with hepatic artery reconstruction in the operation for hilar cholangiocarcinoma (Klatskin tumor) is a challenging procedure. We present a video of left hepatectomy combined with right hepatic artery reconstruction for hilar cholangiocarcinoma. PATIENT AND METHODS: The patient was a 60-year-old male who presented with obstructive jaundice. The imaging examination showed that the confluence of left and right hepatic ducts and the wall of common hepatic duct were thickened, the local lumen was narrowed, the intrahepatic bile duct was dilated, and the right hepatic artery was invaded by tumors nearly 2.3 centimeters. Left hepatectomy with total caudate lobectomy, resection with reconstruction of right hepatic artery, hilar lymphadenectomy, and Roux-en-Y hepaticojejunostomy were performed. RESULTS: The operation time was 345 min, and the amount of bleeding was about 400 ml. There was no blood transfusion. The pathology showed poorly differentiated adenocarcinoma, with negative margins of common bile duct and right hepatic duct, and negative results of all lymph nodes. The patient's recovery was uneventful and he was discharged on postoperative day 14. The patient was disease free at 12-month follow-up evaluation. CONCLUSIONS: Hepatic artery resection and reconstruction procedure is safe and feasible for hilar cholangiocarcinoma in a highly tertiary hepatobiliary center.

Association between Human Blood Proteome and the Risk of Myocardial Infarction.

Background: The objective of this study is to estimate the causal relationship between plasma proteins and myocardial infarction (MI) through Mendelian randomization (MR), predict potential target-mediated side effects associated with protein interventions, and ensure a comprehensive assessment of clinical safety. Methods: From 3 proteome genome-wide association studies (GWASs) involving 9775 European participants, 331 unique blood proteins were screened and chosed. The summary data related to MI were derived from a GWAS meta-analysis, incorporating approximately 61,000 cases and 577,000 controls. The assessment of associations between blood proteins and MI was conducted through MR analyses. A phenome-wide MR (Phe-MR) analysis was subsequently employed to determine the potential on-target side effects of protein interventions. Results: Causal mediators for MI were identified, encompassing cardiotrophin-1 (CT-1) (odds ratio [OR] per SD increase: 1.16; 95% confidence interval [CI]: 1.13-1.18; p = 1.29 × 10 - 31 ), Selenoprotein S (SELENOS) (OR: 1.16; 95% CI: 1.13-1.20; p = 4.73 × 10 - 24 ), killer cell immunoglobulin-like receptor 2DS2 (KIR2DS2) (OR: 0.93; 95% CI: 0.90-0.96; p = 1.08 × 10 - 5 ), vacuolar protein sorting-associated protein 29 (VPS29) (OR: 0.92; 95% CI: 0.90-0.94; p = 8.05 × 10 - 13 ), and histo-blood group ABO system transferase (NAGAT) (OR: 1.05; 95% CI: 1.03-1.07; p = 1.41 × 10 - 5 ). In the Phe-MR analysis, memory loss risk was mediated by CT-1, VPS29 exhibited favorable effects on the risk of 5 diseases, and KIR2DS2 showed no predicted detrimental side effects. Conclusions: Elevated genetic predictions of KIR2DS2 and VPS29 appear to be linked to a reduced risk of MI, whereas an increased risk is associated with CT-1, SELENOS, and NAGAT. The characterization of side effect profiles aids in the prioritization of drug targets. Notably, KIR2DS2 emerges as a potentially promising target for preventing and treating MI, devoid of predicted detrimental side effects.

Multi-omics analysis of gut-brain axis reveals novel microbial and neurotransmitter signatures in patients with arteriosclerotic cerebral small vessel disease.

Arteriosclerotic cerebral small vessel disease (aCSVD) is a major cause of stroke and dementia. Although its underlying pathogenesis remains poorly understood, both inflammaging and gut microbiota dysbiosis have been hypothesized to play significant roles. This study investigated the role of gut microbiota in the pathogenesis of aCSVD through a comparative analysis of the gut microbiome and metabolome between CSVD patients and healthy controls. The results showed that patients with aCSVD exhibited a marked reduction in potentially beneficial bacterial species, such as Faecalibacterium prausnitzli and Roseburia intestinalis, alongside an increase in taxa from Bacteroides and Proteobacteria. Integrated metagenomic and metabolomic analyses revealed that alterations in microbial metabolic pathways, including LPS biosynthesis and phenylalanine-tyrosine metabolism, were associated with the status of aCSVD. Our findings indicated that microbial LPS biosynthesis and phenylalanine-tyrosine metabolism potentially influenced the symptoms and progression of aCSVD via pro-inflammatory effect and modulation of systemic neurotransmitters, respectively. These results imply that gut microbiota characteristics may serve as indicators for early detection of aCSVD and as potential gut-directed therapeutic intervention target.

Transient secretion of VEGF protein from transplanted hiPSC-CMs enhances engraftment and improves rat heart function post MI.

Cell-based therapies offer an exciting and novel treatment for heart repair following myocardial infarction (MI). However, these therapies often suffer from poor cell viability and engraftment rates, which involve many factors, including the hypoxic conditions of the infarct environment. Meanwhile, vascular endothelial growth factor (VEGF) has previously been employed as a therapeutic agent to limit myocardial damage and simultaneously induce neovascularization. This study took an approach to transiently overexpress VEGF protein, in a controlled manner, by transfecting human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with VEGF mRNA prior to transplantation. The conditioning of iPSC-CMs with VEGF mRNA ultimately led to greater survival rates of the transplanted cells, which promoted a stable vascular network in the grafted region. Furthermore, bulk RNA transcriptomics data and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) and AGE-RAGE signaling pathways were significantly upregulated in the VEGF-treated iPSC-CMs group. The over-expression of VEGF from iPSC-CMs stimulated cell proliferation and partially attenuated the hypoxic environment in the infarcted area, resulting in reduced ventricular remodeling. This study provides a valuable solution for the survival of transplanted cells in tissue-engineered heart regeneration and may further promote the application of modified mRNA (modRNA) in the field of tissue engineering.

Evaluation of Confocal Laser Scanning Microscopy in Histological Classification and Photodynamic Therapy of Low-risk Basal Cell Carcinoma.

BACKGROUND: Confocal laser scanning microscopy (CLSM) is noninvasive technique utilized for identification and analysis skin malignancies. Several studies have applied CLSM in monitoring the therapeutic effects of basal cell carcinoma (BCC). OBJECTIVE: To investigate the diagnostic value of CLSM in low-risk BCC and the evaluation of photodynamic therapy (PDT). METHODS: We have diagnosed 149 patients with BCC using CLSM and histopathological examination. Based on histopathology, we summarized the classification information of low-risk BCC along with imaging features observed through CLSM. Thirty-four low-risk BCC patients underwent PDT treatment, and we used CLSM to evaluate its efficacy. RESULTS: Out of 149 participants were diagnosed with BCC by CLSM, 52 were pigmented type, 87 were nodular type and 10 were superficial type. After histopathological examination, 44 out of 52 were pigmented type, five were nodular type and three were superficial type. The results of CLSM were consistent with those of 87 nodular type and 10 superficial type. The CLSM features of nodular were observed in the tissue fissures around the tumor, the pigment mass was the CLSM characteristic of pigmented type. The simultaneous occurrence of inflammation and increased vasculature were characteristics of superficial. The effective rate of PDT was 100%, and the cure rate was 67.6%. At 12 months follow up, the recurrence rate of PDT was 11.8%, 15.0% for nodule type, 10.0% for pigmented type and 0% for superficial type. CONCLUSION: The tissue classification of CLSM for low-risk BCC was consistent with histopathology. CLSM can be used to monitor the efficacy of PDT for low-risk BCC.

Chinese version of the Physical Resilience Scale (PRS): reliability and validity test based on Rasch analysis.

BACKGROUND: Physical resilience is known to minimize the adverse outcomes of health stressors for older people. However, validated instruments that assess physical resilience in older adults are rare. Therefore, the purpose of this study was to translate the Physical Resilience Scale (PRS) into Chinese and to validate its psychometric properties in a population of community-dwelling older adults following SARS-CoV-2 infection. METHODS: This study used a cross-sectional design and translated the Physical Resilience Scale into Chinese. A total of 426 older adults who had recovered from SARS-CoV-2 infection were chosen for assessment through convenience sampling. The measurement data were analyzed using the Rasch analysis. RESULTS: Rasch analysis indicates that the Physical Resilience Scale demonstrates excellent reliability, validity, and unidimensionality. The Infit MNSQ and Outfit MNSQ of each entry were 0.77 ~ 1.19, and the degree of fit of each entry to the scale was good. Person and item separation reliability support the internal consistency of the studied samples and PRS items. CONCLUSIONS: The Physical Resilience Scale has good reliability and is suitable for the assessment of physical resilience tests in older people. However, the overall difficulty of the scale is not suitable for older adults of all ability ranges, and it is possible to add higher and lower difficulty items and adjust the difficulty spacing between items in a later study.

Chronic diseases spectrum and multimorbidity in elderly inpatients based on a 12-year epidemiological survey in China.

BACKGROUND: The number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly. METHODS: A clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients. RESULTS: A total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%. CONCLUSIONS: By analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.

Efficacy of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in hepatocellular carcinoma with macrovascular invasion: a single-center retrospective analysis.

Objective The influence of macrovascular invasion on the therapeutic efficacy of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) in hepatocellular carcinoma (HCC) patients has not been previously reported. This study primarily examines the therapeutic effect of ALPPS in treating HCC with macrovascular invasion. Methods 89 patients who underwent ALPPS at the First Affiliated Hospital of Guangxi Medical University from December 2016 to December 2021 were included. Patients were categorized into three groups based on macrovascular invasion status: pure HCC, HCC with portal vein tumor thrombus (PVTT), and HCC with hepatic vein tumor thrombus (HVTT). Outcome measures such as postoperative complications, liver hyperplasia rates, and survival times were compared across the groups. Results The study comprised 44 patients without macrovascular invasion and 45 cases with it, including 37 PVTT and 8 HVTT cases. Patients with PVTT or HVTT had a higher rate of complications and liver failure after the first ALPPS stage compared to those without macrovascular invasion (P = 0.018, P = 0.036). This trend was also observed in the stratified analysis of severe complications. However, no significant differences were found in these outcomes after the second ALPPS stage among the groups. The volume and rate of future liver remnant proliferation between the two stages of ALPPS were not statistically different among the groups, with median overall survival times of 42, 39, and 33 months, and progression-free survival times of 30, 24, and 14 months, respectively (P = 0.412 and P = 0.281). Conclusion ALPPS for HCC with macrovascular invasion was considered safe, feasible, and effective, as it achieved therapeutic effects comparable to those in cases without macrovascular invasion.

Prevalence and risk factors of sarcopenia in patients on maintenance hemodialysis: a retrospective cohort study.

BACKGROUND: This study aimed to explore the prevalence and related risk factors of sarcopenia in patients on maintenance hemodialysis (MHD). METHODS: This cohort study enrolled 165 patients on MHD. The patients were divided into sarcopenia and non-sarcopenia groups based on the presence of sarcopenia or not. Sarcopenia was diagnosed according to the consensus of the Asian Sarcopenia Working Group that considers reduced muscle mass and decreased muscle strength (19). The muscle mass was measured using the multi-frequency bioelectrical impedance (Inbody260) and skeletal muscle index (SMI) was used: <7.0 kg/m2 (male); <5.7 kg/m2 (female) - with muscle mass reduction. The electronic grip dynamometer was used for measuring dominant handgrip strength (HGS) to reflect muscle strength. Male patients with HGS < 28 kg and female patients with HGS < 18 kg were considered with a decrease in muscle strength. The demographic characteristics, laboratory indexes, anthropometrical measurements, body compositions, and InBody score were compared between groups. The multivariate logistic regression was used to explore the risk factors for sarcopenia. RESULTS: Of the 165 patients on MHD, 36 had sarcopenia, and the prevalence was 21.82%. Patients in the sarcopenia group had higher ages and lower body mass index, serum albumin level, circumference of waist, hip, and biceps, handgrip strength, total water content, protein inorganic salt concentrations, skeletal muscle mass, basal metabolic rate, obesity degree, SMI, and body fat content. The multivariate logistic regression showed that age, waist circumference, handgrip strength, and InBody score were influencing factors for sarcopenia in patients on hemodialysis. CONCLUSION: The prevalence of sarcopenia was high in patients on MHD. Higher age, lower waist circumference, lower handgrip strength, and lower InBody score were independent risk factors for sarcopenia in such patients.

A novel technique for NO.253 lymph node dissection and left colic artery preservation to avoid potential postoperative internal hernia in laparoscopic radical resection for rectal cancer.

BACKGROUND: The preservation of the left colic artery (LCA) has emerged as a preferred approach in laparoscopic radical resection for rectal cancer. However, preserving the LCA while simultaneously dissecting the NO.253 lymph node can create a mesenteric defect between the inferior mesenteric artery (IMA), the LCA, and the inferior mesenteric vein (IMV). This defect could act as a potential "hernia ring," increasing the risk of developing an internal hernia after surgery. The objective of this study was to introduce a novel technique designed to mitigate the risk of internal hernia by filling mesenteric defects with autologous tissue. METHODS: This new technique was performed on eighteen patients with rectal cancer between January 2022 and June 2022. First of all, dissected the lymphatic fatty tissue on the main trunk of IMA from its origin until the LCA and sigmoid artery (SA) or superior rectal artery (SRA) were exposed and then NO.253 lymph node was dissected between the IMA, LCA and IMV. Next, the SRA or SRA and IMV were sequentially ligated and cut off at an appropriate location away from the "hernia ring" to preserve the connective tissue between the "hernia ring" and retroperitoneum. Finally, after mobilization of distal sigmoid, on the lateral side of IMV, the descending colon was mobilized cephalad. Patients'preoperative baseline characteristics and intraoperative, postoperative complications were examined. RESULTS: All patients' potential "hernia rings" were closed successfully with our new technique. The median operative time was 195 min, and the median intraoperative blood loss was 55 ml (interquartile range 30-90). The total harvested lymph nodes was 13.0(range12-19). The median times to first flatus and liquid diet intake were both 3.0 days. The median number of postoperative hospital days was 8.0 days. One patient had an injury to marginal arterial arch, and after mobolization of splenic region, tension-free anastomosis was achieved. No other severe postoperative complications such as abdominal infection, anastomotic leakage, or bleeding were observed. CONCLUSIONS: This technique is both safe and effective for filling the mesenteric defect, potentially reducing the risk of internal hernia following laparoscopic NO.253 lymph node dissection and preservation of the left colic artery in rectal cancer surgeries.

Synthesis and Characterization of 3,4-Bis[3(2-azidoethoxy)furazan-4-yl]furoxan (DAeTF): A Novel Low-Melting Insensitive Energetic Material.

The synthesis and characterization of low-melting-point insensitive energetic materials are crucial due to their increasing applications in melt-cast explosives. In this work, a furazan-derived energetic compound, 3,4-bis[3(2-azidoethoxy)furazan-4-yl]furoxan (DAeTF), exhibiting insensitive and high-energy characteristics, is rationally designed and synthesized. The structure of DAeTF is characterized by nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, elemental analysis, mass spectrometry, and single-crystal X-ray diffraction. The thermal properties of DAeTF are investigated using differential scanning calorimetry, in situ FTIR spectroscopy and thermogravimetric-differential scanning calorimetry-Fourier transform infrared-mass spectrometry and thermal decomposition mechanism was elucidated in combination with bond energy calculations. The detonation performance of DAeTF is predicted by the EXPLO5 program. The results indicate that DAeTF has thermal stability (Td = 251.7 °C), high energy level (D = 7270 m/s) and significant insensitivity (IS = 60 J). Additionally, its relatively low melting point (Tm = 60.5 °C) facilitates processing and loading. These characteristics indicate that DAeTF is a promising candidate as an insensitive melt-cast explosive in future applications.

Chinese version of the Death Anxiety Beliefs and Behaviours Scale: Psychometric properties based on CTT and IRT.

OBJECTIVES: The Death Anxiety Beliefs and Behaviour Scale (DABBS) is a unique tool designed to assess the detrimental beliefs and avoidant behaviors linked to death anxiety. This study aimed to adapt the DABBS into Chinese and verify its psychometric characteristics within a community-dwelling older adult population. METHODS: This study used a cross-sectional design and translated the DABBS into Chinese. The psychometric properties of 437 community-dwelling older persons were assessed using the Classical Test Theory (CTT) and Item Response Theory (IRT). RESULTS: The DABBS consisted of affect, beliefs, and behaviours, with 18 entries in 3 dimensions. The I-CVI of the DABBS ranged from 0.857 to 1.000, and the S-CVI was 0.968; Cronbach's alpha of 0.905. Rasch analysis results showed that the 3 dimensions of the scale possessed good unidimensionality, and the entries were well-fitted to the dimensions in which they were located; each entry Infit MNSQ and Outfit MNSQ were in the range of 0.50 to 1.50; the analysis of the functional differences of items in different characteristic subgroups (gender) showed that the absolute value of DIF Contrast was <0.50. The results of the Wright map showed that the ability of the participants was normally distributed, and the difficulty of the scale's entries was adapted to the average ability level of older adults. CONCLUSIONS: The present data indicate that the revised DABBS is a valid and reliable tool for assessing affect, beliefs, and behaviors associated with death anxiety in community-dwelling older individuals.

Prevalence and risk factors of training-related abdominal injuries: A multicenter survey study.

PURPOSE: This study aims to identify the prevalence and risk factors of military training-related abdominal injuries and help plan and conduct training properly. METHODS: This questionnaire survey study was conducted from October 2021 to May 2022 among military personnel from 6 military units and 8 military medical centers and participants' medical records were consulted to identify the training-related abdominal injuries. All the military personnel who ever participated in military training were included. Those who refused to participate in this study or provided an incomplete questionnaire were excluded. The questionnaire collected demographic information, type of abdominal injury, frequency, training subjects, triggers, treatment, and training disturbance. Chi-square test and t-test were used to compare baseline information. Univariate and multivariate regression analyses were used to explore the risk factors associated with military training-related abdominal injuries. RESULTS: A total of 3058 participants were involved in this study, among which 1797 (58.8%) had suffered training-related abdominal injuries (the mean age was 24.3 years and the service time was 5.6 years), while 1261 (41.2%) had no training-related abdominal injuries (the mean age was 23.1 years and the service time was 4.3 years). There were 546 injured patients (30.4%) suspended the training and 84 (4.6%) needed to be referred to higher-level hospitals. The most common triggers included inadequate warm-up, fatigue, and intense training. The training subjects with the most abdominal injuries were long-distance running (589, 32.8%). Civil servants had the highest rate of abdominal trauma (17.1%). Age ≥ 25 years, military service ≥ 3 years, poor sleep status, and previous abdominal history were independent risk factors for training-related abdominal injury. CONCLUSION: More than half of the military personnel have suffered military training-related abdominal injuries. Inadequate warm-up, fatigue, and high training intensity are the most common inducing factors. Scientific and proper training should be conducted according to the factors causing abdominal injuries.

[Comparison on tissue distribution of five components in Shuganning Injection and Scutellariae Radix extract by UPLC-MS/MS].

This study established an ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method to determine the content of five index components in rat tissues and organs after administration of Shuganning Injection or Scutellariae Radix extract. The dynamic changes and differences of the distribution of the five index components over time between the two groups were studied, and the effects of Scutellariae Radix alone or in combination with other medicines on the tissue distribution of the five components were explored. After Shuganning Injection or Scutellariae Radix extract was injected into the tail vein of rats, the heart, liver, spleen, lung, kidney, stomach, intestine, and brain tissue samples were collected at four time points of 0.17, 0.5, 1, and 2 h, respectively. UPLC-MS/MS was employed to measure the concentrations of the five index components(baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin) in the samples of the two groups. The results showed that the established method was simple, fast, and exclusively stable. After the administration of Shuganning Injection and Scutellariae Radix extract, the five index components presented wide distribution and had differences in vivo. The two groups showcased abundant distribution of baicalin, baicalein, and oroxylin A in the kidney and liver, oroxylin A-7-O-ß-D-glucuronide in the kidney and brain, and scutellarin in the kidney and heart. The content of baicalin in the heart, liver, kidney, and intestine, baicalein in the liver and kidney, and oroxylin A in the lung after administration of Shuganning Injection(Scutellariae Radix in combination with other medicines) was significantly higher than that after administration of Scutellariae Radix extract. The results of this study suggested that the five components of Shuganning Injection and Scutellariae Radix extract demonstrated wide distribution without accumulation in rats. The combination of Scutellariae Radix with other medicines can increase the distribution of active components in rats, which provided a basis for explaining the rationality of the compatibility of Shuganning Injection from in vivo processes.

MDFI regulates fast-to-slow muscle fiber type transformation via the calcium signaling pathway.

Muscle fiber is the basic unit of skeletal muscle with strong self-adaptability, and its type is closely related to meat quality. Myod family inhibitor (Mdfi) has the function of regulating myogenic regulatory factors during cell differentiation, but how Mdfi regulates muscle fiber type transformation in myoblasts is still unclear. In the present study, we constructed overexpressing and interfering with Mdfi C2C12 cell models by lipofection. The immunofluorescence, quantitative real-time PCR (qPCR), and western blot results show that the elevated MDFI promoted mitochondrial biogenesis, aerobic metabolism and the calcium level by activating CaMKK2 and AMPK phosphorylation and then stimulated the conversion of C2C12 cells from fast glycolytic to slow oxidative type. In addition, after inhibiting IP3R and RYR channels, the higher MDFI reversed the blockage of calcium release from the endoplasmic reticulum by calcium channel receptor inhibitors and increased intracellular calcium levels. Therefore, we propose that the higher MDFI promotes muscle fiber types conversion through the calcium signaling pathway. These findings further broaden our understanding of the regulatory mechanism of MDFI in muscle fiber type transformation. Furthermore, our results suggest potential therapeutic targets for skeletal muscle and metabolic-related diseases.

Transfer of patient's peripheral blood mononuclear cells (PBMCs) disrupts blood-brain barrier and induces anti-NMDAR encephalitis: a study of novel humanized PBMC mouse model.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neuropsychiatric disease. Brain access of anti-NMDAR autoantibody through the blood-brain barrier (BBB) is essential for pathogenesis. Most previous animal models limit the investigation of etiologies of BBB damage in patients. METHODS: In this study, we established a novel humanized mouse model of anti-NMDAR encephalitis by intraperitoneal injection of patients' peripheral blood mononuclear cells (PBMCs) into BALB/c Rag2-/-Il2rg-/-SirpαNODFlk2-/- mice. RESULTS: We found that engraftment of patients' PBMCs not only produced potent anti-GluN1 autoantibodies, but also disrupted BBB integrity to allow brain access of autoantibodies, resulting in a hyperactive locomotor phenotype, anxiety- and depressive-like behaviors, cognitive deficits, as well as functional changes in corresponding brain regions. Transcriptome analysis suggested an exaggerated immune response and impaired neurotransmission in the mouse model and highlighted Il-1ß as a hub gene implicated in pathological changes. We further demonstrated that Il-1ß was produced by endothelial cells and disrupted BBB by repressing tight junction proteins. Treatment with Anakinra, an Il-1 receptor antagonist, ameliorated BBB damage and neuropsychiatric behaviors. CONCLUSIONS: Our study provided a novel and clinically more relevant humanized mouse model of anti-NMDAR encephalitis and revealed an intrinsic pathogenic property of the patient's lymphocytes.

PDZ-binding kinase aggravates pancreatic neuroendocrine neoplasm progression by activating the AKT/mTOR pathway.

The therapeutic effects of existing drug regimens against pancreatic neuroendocrine neoplasms (pNENs) remain limited, and identifying ideal therapeutic targets is warranted. PDZ binding kinase (PBK) may play an oncogenic role in most solid tumors. However, its function in pNEN remains unclear. In this study, pNEN samples and International Cancer Genome Consortium data were used to determine the clinical significance of PBK. Cell counting and CCK8 assays were used to assess cell proliferation. Flow cytometry was used to assess drug-induced apoptosis and cell cycle arrest. An in vivo PBK-targeting experiment was performed in mice bearing pNENs. Western blotting, quantitative PCR, and immunohistochemistry were performed to assess the molecular mechanisms. PBK was significantly upregulated in pNEN tissues compared with paracancerous tissues. Additionally, PBK was a poor prognostic factor for pNEN patients. PBK was found to promote the proliferation of pNEN cells by activating the AKT/mTOR pathway. Furthermore, PBK inhibition combined with everolimus treatment had enhanced antitumour effects on pNEN via inhibiting AKT/mTOR pathway and inducing G0/G1 phase cell cycle arrest. This study highlights that PBK plays an oncogenic role in and is a promising therapeutic target for pNEN.

Metabolic engineering of oleaginous yeast in the lipogenic phase enhances production of nervonic acid.

Insufficient biosynthesis efficiency during the lipogenic phase can be a major obstacle to engineering oleaginous yeasts to overproduce very long-chain fatty acids (VLCFAs). Taking nervonic acid (NA, C24:1) as an example, we overcame the bottleneck to overproduce NA in an engineered Rhodosporidium toruloides by improving the biosynthesis of VLCFAs during the lipogenic phase. First, evaluating the catalytic preferences of three plant-derived ketoacyl-CoA synthases (KCSs) rationally guided reconstructing an efficient NA biosynthetic pathway in R. toruloides. More importantly, a genome-wide transcriptional analysis endowed clues to strengthen the fatty acid elongation (FAE) module and identify/use lipogenic phase-activated promoter, collectively addressing the stagnation of NA accumulation during the lipogenic phase. The best-designed strain exhibited a high NA content (as the major component in total fatty acid [TFA], 46.3%) and produced a titer of 44.2 g/L in a 5 L bioreactor. The strategy developed here provides an engineering framework to establish the microbial process of producing valuable VLCFAs in oleaginous yeasts.

LINC00115 regulates lung adenocarcinoma progression via sponging miR-154-3p to modulate Sp3 expression.

The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.