Sesquiterpenoids from the roots and rhizomes of Valeriana officinalis var. latifolia.

The genus Valeriana is used in traditional Chinese medicine to treat nervous disorders, sleep disorders, epilepsy and skin diseases. A large number of sesquiterpenoids from this genus have been found to exhibit anti-inflammatory, antiproliferative, anti-influenza virus and neuroprotective activities. In order to discover more sesquiterpenoids with structural diversity and bioactivity from Valeriana plants, fifteen sesquiterpenoids, including ten undescribed ones, valernaenes A-J (1, 5-7, 9-11 and 13-15), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated by extensive spectroscopic techniques (1D, 2D NMR and HRESIMS) and electronic circular dichroism (ECD) calculation. Structurally, valernaenes C (6) and D (7) were two caryophyllane-type norsesquiterpenoids. In addition, valernaenes A (1) and F (10) exhibited anti-influenza virus activity with EC50 values of 38.76 ± 1.44 and 23.01 ± 4.89 µM, respectively. Furthermore, caryophyllenol A (2) showed promoting effect on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells with differentiation rate of 12.26% at a concentration of 10 µM. This study not only enriched the structural diversity of sesquiterpenoids in the genus Valeriana, but also provided theoretical basis for the discovery of anti-influenza virus and neuroprotective agents from this genus.

Monosome Stalls the Translation Process Mediated by IGF2BP in Arcuate Nucleus for Puberty Onset Delay.

Puberty onset through hypothalamic-pituitary-gonad (HPG) axis as an important reproductive event in postnatal development is initiated from hypothalamic arcuate nucleus (ARC). The growing evidence indicates that translational control also plays an essential role in the final expression of gonadotropin genes. To investigate the role of protein translation and behavior of ribosomes in pubertal onset, the global profiles of transcriptome, single ribosome (monosome), polysome, and tandem mass tag proteome were comprehensively investigated in rat hypothalamic ARCs of different pubertal stages using RNA sequencing, polyribo sequencing, and mass spectrum. Transcriptome-wide enrichments of N6-methyladenosine and IGF2BP2 were investigated using meRIP and RIP sequencing. Monosome was robustly enriched on a large proportion of mRNA in early puberty rats (postnatal day (PND)-25) compared to late puberty (PND-35 and PND-45). Monosome-enriched mRNAs, including HPG axis-related genes, had a large number of upstream ORFs (uORF, < 100 nt) and displayed translational repression in early puberty. Furthermore, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could particularly interact with and facilitate monosome to bind with mRNA in early puberty. Finally, ectopic over-expression of IGF2BP2 in hypothalamic ARC via lateral ventricle injection in vivo could recruit monosome to aggregate on mRNA and delay puberty onset. We uncovered a novel regulatory mechanism of IGF2BP2 and monosome for translational control in puberty onset, which shed light on the neuroendocrine regulatory network involved in HPG axis activation.

A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity.

Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (1-3) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex 3). In addition, a control compound (complex 4) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes 1-3 was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order 3 > 2 > 1, giving the IC50 values ranging from 2.874 ± 0.155 µM to 31.47 ± 0.29 µM against five cancer cell lines. Complex 4 showed less activity in comparison with complex 1-3. Notably, complexes 1-3 displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex 4 (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound 3 induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes 3 and 4 was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex 3 interacted with DNA in an intercalating mode, but the interaction mode of compound 4 with DNA was electrostatic interaction.

Recent clinical researches and technological development in TIL therapy.

Tumor-infiltrating lymphocyte (TIL) therapy represents a groundbreaking advancement in the solid cancer treatment, offering new hope to patients and their families with high response rates and long overall survival. TIL therapy involves extracting immune cells from a patient's tumor tissue, expanding them ex vivo, and infusing them back into the patient to target and eliminate cancer cells. This revolutionary approach harnesses the power of the immune system to combat cancers, ushering in a new era of T cell-based therapies along with CAR-T and TCR-therapies. In this comprehensive review, we aim to elucidate the remarkable potential of TIL therapy by delving into recent advancements in basic and clinical researches. We highlight on the evolving landscape of TIL therapy as a prominent immunotherapeutic strategy, its multifaceted applications, and the promising outcomes. Additionally, we explore the future horizons of TIL therapy, next-generation TILs, and combination therapy, to overcome the limitations and improve clinical efficacy of TIL therapy.

A low-swelling alginate hydrogel with antibacterial hemostatic and radical scavenging properties for open wound healing.

Development of a low-cost and biocompatible hydrogel dressing with antimicrobial, antioxidant, and low swelling properties is important for accelerating wound healing. Here, a multifunctional alginate hydrogel dressing was fabricated using the D-(+)-gluconic acidδ-lactone/CaCO3system. The addition of hyaluronic acid and tannic acid (TA) provides the alginate hydrogel with anti-reactive oxygen species (ROS), hemostatic, and pro-wound healing properties. Notably, soaking the alginate hydrogel in a poly-ϵ-lysine (EPL) aqueous solution enables the alginate hydrogel to be di-crosslinked with EPL through electrostatic interactions, forming a dense network resembling 'armor' on the surface. This simple one-step soaking strategy provides the alginate hydrogel with antibacterial and anti-swelling properties. Swelling tests demonstrated that the cross-sectional area of the fully swollen multifunctional alginate hydrogel was only 1.3 times its initial size, thus preventing excessive wound expansion caused by excessive swelling. After 5 h ofin vitrorelease, only 7% of TA was cumulatively released, indicating a distinctly slow-release behavior. Furthermore, as evidenced by the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals, this integrated alginate hydrogel systems demonstrate a notable capacity to eliminate ROS. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed multifunctional alginate hydrogels have a prominent effect on extracellular matrix formation and promotion of wound closure. Overall, this study introduces a cost-effective and convenient multifunctional hydrogel dressing with high potential for clinical application in treating open wounds.

Near-Electrode Concentration Gradients of Bicarbonate and pH within Porous Gas Diffusion Electrode for Optimized Selective CO2 Electroreduction to C2+ Products.

With high current density, the intense near-electrode CO2 reduction reaction (CO2RR) will cause the concentration gradients of bicarbonate (HCO3-) and hydroxyl (OH-) ions, which affect the selectivity of high-value C2+ products of the CO2RR. In this work, we simulated the near-electrode concentration gradients of electrolyte species with different porous Cu-based CLs (catalyst layers) of GDE (gas diffusion electrode) by COMSOL Multiphysics. The higher porosity CL exhibits a better buffer ability of local alkalinity while ensuring a sufficient supply of H+ and local CO2 concentration. Subsequently, the different porosity CLs were prepared by vacuum-thermal evaporation with different evaporation rate. Structural characterizations and liquid permeability tests confirm the role of the porous CL structure in optimizing concentration gradients. As a result, the high-porosity CL (Cu-HP) exhibits a higher C2+ Faraday efficiency (FE) of ∼79.61% at 500 mA cm-2 under 1 M KHCO3, far more than the FEC2+ ≈ 38.20% with the low-porosity sample (Cu-LP).

Efficacy and Safety of Pioglitazone/Metformin Fixed-Dose Combination Versus Uptitrated Metformin in Patients with Type 2 Diabetes without Adequate Glycemic Control: A Randomized Clinical Trial.

INTRODUCTION: We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. METHODS: A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500 mg) or the control group (uptitrated metformin, 2000-2500 mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. RESULTS: In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. CONCLUSIONS: Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. TRIAL REGISTRATION NUMBER: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).

GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain: A Phase 3 Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants: This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration: ClinicalTrials.gov Identifier: NCT04647773.

Accelerating Toluene Oxidation over Boron-Titanium-Oxygen Interface: Steric Hindrance of the Methyl Group Induced by the Plane-Adsorption Configuration.

Elimination of dilute gaseous toluene is one of the critical concerns within the field of indoor air remediation. The typical degradation route on titanium-based catalysts, "toluene-benzaldehyde-carbon dioxide", necessitates the oxidation of the methyl group as a prerequisite for photocatalytic toluene oxidation. However, the inherent planar adsorption configuration of toluene molecules, dominated by the benzene rings, leads to significant steric hindrance for the methyl group. This steric hindrance prevents the methyl group from contacting the active species on the catalyst surface, thereby limiting the removal of toluene under indoor conditions. To date, no effective strategy to control the steric hindrance of the methyl group has been identified. Herein, we showed a B-Ti-O interface that exhibits significantly enhanced toluene removal efficiency under indoor conditions. In-depth investigations revealed that, compared to typical Ti-based photocatalysts, the steric hindrance between the methyl group and the catalyst surface decreased from 3.42 to 3.03 Å on the designed interface. This reduction originates from the matching of orbital energy levels between Ti 3dz2 and C 2pz of the benzene ring. The decreased steric hindrance improved the efficiency of toluene being attacked by surface active species, allowing for rapid conversion into benzaldehyde and benzoic acid species for subsequent reactions. Our work provides novel insights into the steric hindrance effect in the elimination of aromatic volatile organic compounds.

Toxicity to the Male Reproductive System after Exposure to Polystyrene Nanoplastics: A Macrogenomic and Metabolomic Analysis.

Nanoplastics (NPs) cause serious contamination of drinking water and potential damage to human health. This study aimed to investigate the effects of NPs with different particle sizes and concentrations on the reproductive function of male mice. In this study, free drinking water exposure was used to expose male BALB/C mice to PS-NPs (20 nm, 200 nm, and 1000 nm) at 0.1 mg/L, 1 mg/L, and 5 mg/L for 4 months. The male reproductive function of the mice was assessed after NPs exposure, and fecal and blood samples were collected for macrogenomics and metabolomics. The results showed that PS-NPs resulted in mice with reduced testicular organ coefficients, decreased sperm quality, altered testicular tissue structure, disturbed sex hormone levels, and abnormal levels of inflammatory factors and oxidative stress. Furthermore, this study found that NP exposure affected the alteration of gut communities and metabolic pathways related to male reproduction, such as Clostridium and glutathione metabolism. Importantly, we found an effect of NP particle size on reproductive function. In the future, more attention should be paid to the smaller particle sizes of NPs.

Optimizing Defibrillator Deployment with Bus-Mounted Automated External Defibrillator.

OBJECTIVES: Early defibrillation with an automated external defibrillator (AED) can effectively improve the survival rate of patients with out-of-hospital cardiac arrest (OHCA). Placing AEDs in public locations can reduce the defibrillation response interval from collapse to defibrillation. Most public AEDs are currently placed in a stationary way (S-AED) with limited coverage area. Bus mounted AED (B-AED) can be delivered directly to the demand point. Although B-AEDs are only available during bus operating hours, they provide greater coverage area. When the number of available AEDs is insufficient, better coverage may be achieved by placing a portion of AEDs as B-AEDs. Our purpose is developing a model to determine the optimal locations of B-AEDs and S-AEDs with a predetermined number of available AEDs. The goal is to maximize the total coverage level of all demand points. METHODS: We proposed a joint location model to place B-AEDs and S-AEDs based on the p-median problem (JPMP). Using data from Chang'an District, Xi'an City, China, we determined the optimal AED deployment. The performance of JPMP was compared with several other models. The coverage results of JPMP are analyzed in details, including the quantity assignment, coverage level, and geographical location of B-AEDs and S-AEDs. The impact of the bus departure intervals on coverage was also discussed. RESULTS: The use of B-AEDs results in an average 98.43% increase in the number of covered demand points, and an average 74.05% increase in total coverage level. In optimal AED deployment, B-AEDs coverage follows an inverted U-shaped curve with increasing number of available AEDs. It begins to decrease when all demand points during the operating hours are covered. With a constant number of available AEDs, the total coverage level increases and then decreases as the bus departure interval increases. The larger the number of available AEDs, the smaller the optimal departure interval. CONCLUSIONS: With a given number of available AEDs, combinational deployment of B-AEDs and S-AEDs significantly improves the coverage level. B-AEDs are recommended when AEDs are insufficient. If more AEDs are available, better coverage can be obtained with reasonable location of S-AEDs and B-AEDs.

Synergistic Biocontrol and Growth Promotion in Strawberries by Co-Cultured Trichoderma harzianum TW21990 and Burkholderia vietnamiensis B418.

This study aimed to investigate the efficiency of the secondary metabolites (SMs) produced by a co-culture of Trichoderma harzianum TW21990 and Burkholderia vietnamiensis B418 in the control of Colletotrichum siamense CM9. A fermentation filtrate of B418 + TW21990 co-culture (BT21) produced a notable increase in the inhibition rate of CM9 compared to those of TW21990 and B418 monocultures, which reached 91.40% and 80.46% on PDA plates and strawberry leaves, respectively. The BT21 fermentation broth exhibited high control efficiency on strawberry root rot of 68.95% in a pot experiment, which was higher than that in the monocultures and fluazinam treatment. In addition, BT21 treatment promoted strawberry root development, improved antioxidative enzyme activities in the leaves and roots, and enhanced the total chlorophyll content of the strawberry leaves. UHPLC-MS/MS analysis of fermentation filtrates was performed to elucidate SM variations, revealing 478 and 795 metabolites in BT21 co-culture in positive and negative ion modes, respectively. The metabolomic profiles suggested abundant SMs with antagonistic capabilities and growth-promoting effects: 3-(propan-2-yl)-octahydropyrrolo [1,2-a]pyrazine-1,4-dione (cyclo(L-Pro-L-Val)), 3-[(4-hydroxyphenyl)methyl]-octahydropyrrolo[1,2-a]pyrazine-1,4-dione (cyclo(L-Pro-L-Tyr)), 3-indoleacetic acid (IAA), 2-hydroxycinnamic acid, 4-aminobutyric acid (GABA), bafilomycin B1, and DL-indole-3-lactic acid (ILA) were significantly enhanced in the co-culture. Overall, this study demonstrates that a co-culture strategy is efficient for inducing bioactive SMs in T. harzianum and B. vietnamiensis, which could be exploited as a novel approach for developing biocontrol consortia.

Endothelial α1-adrenergic receptor activation improves cardiac function in septic mice via PKC-ERK/p38MAPK signaling pathway.

Cardiomyopathy is particularly common in septic patients. Our previous studies have shown that activation of the alpha 1 adrenergic receptor (α1-AR) on cardiomyocytes inhibits sepsis-induced myocardial dysfunction. However, the role of cardiac endothelial α1-AR in septic cardiomyopathy has not been determined. Here, we identified α1-AR expression in mouse and human endothelial cells and showed that activation of α1-AR with phenylephrine (PE) improved cardiac function and survival by preventing cardiac endothelial injury in septic mice. Mechanistically, activating α1-AR with PE decreased the expression of ICAM-1, VCAM-1, iNOS, E-selectin, and p-p38MAPK, while promoting PKC and ERK1/2 phosphorylation in LPS-treated endothelial cells. These effects were abolished by a PKC inhibitor or α1-AR antagonist. PE also reduced p65 nuclear translocation, but this suppression is not blocked by PKC inhibition. Treatment with U0126 (a specific ERK1/2 inhibitor) reversed the effects of PE on p38MAPK phosphorylation. Our results demonstrate that cardiac endothelial α1-AR activation prevents sepsis-induced myocardial dysfunction in mice by inhibiting the endothelial injury via PKC-ERK/p38MAPK signaling pathway and a PKC-independent inhibition of p65 nuclear translocation. These findings offer a new perspective for septic patients with cardiac dysfunction by inhibiting cardiac endothelial cell injury through α1-AR activation.

Therapeutic effect of iridoid and xanthone glycosides components extracted from Swertia Mussotti on calculous cholecystitis and its clinical complications by targeting COX2.

Swertia Mussotti is used as febrifuge, analgesic and to treat calculous cholecystitis, however, the underling mechanism remains unclear. This study investigates the therapeutic effect of the active fraction named iridoid and xanthone glycoside (IXG) extracted from S. mussotii on six animal models related to calculous cholecystitis and its complications, and to explore its potential target proteins. Four main compounds including swertiamarin (STR), sweroside (SRS), gentiopicroside (GPS) and mangiferin (MGR) were identified from the IXG by UHPLC-TOF-MS. The in vivo experiments results confirmed that IXG significantly decreased the level of total bilirubin (TBIL), direct bilirubin (DBIL) and cyclooxygenase-2 (COX2) in calculous cholecystitis. IXG treatment dramatically reduced the number of twists and the time of clicking foot in 2nd phase induced by glacial acetic acid and formalin, however, no effect was showed on central pain established by hot plate test. IXG also significantly decreased the anal temperature induced by yeast and 2,4-dinitrophenol. These results indicated that IXG alleviate calculous cholecystitis and its clinical symptom. In addition, IXG suppressed the expression of Prostaglandin E2 (PGE2) in vitro. Mechanistically, COX2 was identified as the direct target of IXG in RAW264.7 cells, and downregulated the protein levels of COX2. The results confirmed that IXG ameliorates calculous cholecystitis and its clinical symptom (pain and fever) by suppressing the production of PGE2 through targeting COX2.

Analysis of lake changes and their influence factors in the three river regions from 2000 to 2020 in the Sanjiangyuan Region, China.

An important factor for investigating climate change in the Sanjiangyuan is the evolution of the spatio-temporal pattern of lakes in this region. The present study used the Google Earth Engine (GEE) platform to extract lakes from 2000 to 2020. The present approach created a lake distribution dataset yearly and analyzed spatial and temporal patterns over 20 years. The analysis of lakes focused on the reaction of the Sanjiangyuan Lakes area to changes in climate, glaciers, and permafrost. The findings indicated that the Sanjiangyuan region contains 143 lakes, the majority of which are predominantly small, measuring 1-10 km2. The small lakes account for 60.14 % of the total and are primarily located in the source regions of the Yangtze River and Yellow River. The findings demonstrated that the Sanjiangyuan lakes experienced a significant expansion over the past two decades, particularly from 2011 to 2020. These lakes are divided into expanded, atrophic, and stable categories. Expanded lakes showed significant inter-annual trends in expansion, while atrophic lakes showed smaller fluctuations. The area of stable lakes experienced a consistent decline after 2010, despite a consistent expansion tendency from 2001 to 2010. Moreover, the results indicated that alterations in the size of glaciers and ice reserves in the Sanjiangyuan region have had the greatest influence on the fluctuation in lake area. Among the factors that affect the climate, temperature had the most significant effect on the change in lake area, followed by precipitation.

Application of prostate resectoscope in the treatment of massive rectal bleeding after transrectal prostate puncture.

BACKGROUND: Ultrasound-guided prostate biopsy is a reliable diagnostic procedure for prostate cancer diagnosis with minimal procedure-related trauma. However, complications, such as massive rectal bleeding may occur after the puncture. We hypothesized that using a transrectal resectoscope could help treat massive rectal bleeding after transrectal prostate punctures. AIM: To identify a simple and effective treatment for massive rectal bleeding after transrectal prostate punctures. METHODS: Patients requiring treatment for massive rectal bleeding after transrectal prostate punctures were included. A SIMAI resectoscope was inserted through the anus. Direct electrocoagulation was performed for superficial bleeding points. Part of the rectal mucosa or surface muscle layer was removed to expose deep bleeding points, followed by electrocoagulation. An electric cutting ring was used to compress and stop the bleeding for jet-like points before electrocoagulation. The fluid color in the drainage tube was monitored postoperatively for continuous bleeding. RESULTS: Eight patients were included from 2012 to 2022. None of the patients with massive rectal bleeding after the transrectal prostate punctures improved with conventional conservative and blood transfusion treatments. Two patients had an inferior artery embolism, and digital subtraction angiography was ineffective. All patients received emergency transanal prostate resection, which immediately stopped the bleeding. Four days after the procedure, the patients had recovered and were discharged. CONCLUSION: Using a transanal prostate resection instrument is a simple, safe, and effective method for treating massive rectal bleeding after transrectal prostate punctures.

Correlation between cerebral neurotransmitters levels by proton magnetic resonance spectroscopy and HbA1c in patients with type 2 diabetes.

BACKGROUND: Cognitive dysfunction is the main manifestation of central neuropathy. Although cognitive impairments tend to be overlooked in patients with diabetes mellitus (DM), there is a growing body of evidence linking DM to cognitive dysfunction. Hyperglycemia is closely related to neurological abnormalities, while often disregarded in clinical practice. Changes in cerebral neurotransmitter levels are associated with a variety of neurological abnormalities and may be closely related to blood glucose control in patients with type 2 DM (T2DM). AIM: To evaluate the concentrations of cerebral neurotransmitters in T2DM patients exhibiting different hemoglobin A1c (HbA1c) levels. METHODS: A total of 130 T2DM patients were enrolled at the Department of Endocrinology of Shanghai East Hospital. The participants were divided into four groups according to their HbA1c levels using the interquartile method, namely Q1 (< 7.875%), Q2 (7.875%-9.050%), Q3 (9.050%-11.200%) and Q4 (≥ 11.200%). Clinical data were collected and measured, including age, height, weight, neck/waist/hip circumferences, blood pressure, comorbidities, duration of DM, and biochemical indicators. Meanwhile, neurotransmitters in the left hippocampus and left brainstem area were detected by proton magnetic resonance spectroscopy. RESULTS: The HbA1c level was significantly associated with urinary microalbumin (mALB), triglyceride, low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), and beta cell function (HOMA-ß), N-acetylaspartate/creatine (NAA/Cr), and NAA/choline (NAA/Cho). Spearman correlation analysis showed that mALB, LDL-C, HOMA-IR and NAA/Cr in the left brainstem area were positively correlated with the level of HbA1c (P < 0.05), whereas HOMA-ß was negatively correlated with the HbA1c level (P < 0.05). Ordered multiple logistic regression analysis showed that NAA/Cho [Odds ratio (OR): 1.608, 95% confidence interval (95%CI): 1.004-2.578, P < 0.05], LDL-C (OR: 1.627, 95%CI: 1.119-2.370, P < 0.05), and HOMA-IR (OR: 1.107, 95%CI: 1.031-1.188, P < 0.01) were independent predictors of poor glycemic control. CONCLUSION: The cerebral neurotransmitter concentrations in the left brainstem area in patients with T2DM are closely related to glycemic control, which may be the basis for the changes in cognitive function in diabetic patients.

The growth-promoting and disease-suppressing mechanisms of Trichoderma inoculation on peanut seedlings.

Trichoderma spp. is known for its ability to enhance plant growth and suppress disease, but the mechanisms for its interaction with host plants and pathogens remain unclear. This study investigated the transcriptomics and metabolomics of peanut plants (Arachis hypogaea L.) inoculated with Trichoderma harzianum QT20045, in the absence and presence of the stem rot pathogen Sclerotium rolfsii JN3011. Under the condition without pathogen stress, the peanut seedlings inoculated with QT20045 showed improved root length and plant weight, increased indole acetic acid (IAA) production, and reduced ethylene level, with more active 1-aminocyclopropane-1-carboxylate acid (ACC) synthase (ACS) and ACC oxidase (ACO), compared with the non-inoculated control. Under the pathogen stress, the biocontrol efficacy of QT20045 against S. rolfsii was 78.51%, with a similar effect on plant growth, and IAA and ethylene metabolisms to the condition with no biotic stress. Transcriptomic analysis of peanut root revealed that Trichoderma inoculation upregulated the expression of certain genes in the IAA family but downregulated the genes in the ACO family (AhACO1 and AhACO) and ACS family (AhACS3 and AhACS1) consistently in the absence and presence of pathogens. During pathogen stress, QT20045 inoculation leads to the downregulation of the genes in the pectinesterase family to keep the host plant's cell wall stable, along with upregulation of the AhSUMM2 gene to activate plant defense responses. In vitro antagonistic test confirmed that QT20045 suppressed S. rolfsii growth through mechanisms of mycelial entanglement, papillary protrusions, and decomposition. Our findings highlight that Trichoderma inoculation is a promising tool for sustainable agriculture, offering multiple benefits from pathogen control to enhanced plant growth and soil health.