Psychological stressors involved in the pathogenesis of premature ovarian insufficiency and potential intervention measures.

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.

Enhancing acoustic emission wave attenuation at structural boundaries: Introducing an additional spiral acoustic black hole and assessing its performance.

Acoustic emission (AE) technology plays a crucial role in dynamic nondestructive testing. To investigate material properties, friction characteristics, damage features, and acoustic source localization, AE tests are commonly conducted on metal or composite plates. However, the reflection of AE waves at the boundary often generates strong interference, significantly impacting AE test results. In response to this challenge, this paper introduces an innovative solution: an additional Spiral Acoustic Black Hole (ASABH) affixed to the test plate's boundary. The ASABH is designed to mitigate the reflection of AE signals, enhancing the signal-to-noise ratio collected by the sensor. The study begins by establishing a finite element model of the ASABH to validate its efficacy in reducing boundary reflection waves. Subsequently, the paper explores the impact of structural geometric parameters-such as length, residual thickness, power exponent, pitch, and extended length-on the reduction effect. The investigation also delves into the variation of attenuation degree when connecting the ASABH to plates with different relative thickness, relative widths, and materials. Finally, the effectiveness of the ASABH in attenuating structural boundary reflection waves is verified through pencil-lead breaking tests conducted on both metal and composite plates. Results indicate that the proposed ASABH effectively mitigates the reflection of AE waves at the structural boundary, demonstrating adaptability and providing valuable insights for ASABH design.

High Manganese Content of Lipid NanoMn (LNM) by Microfluidic Technology for Enhancing Anti-Tumor Immunity.

Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.

A novel waveguide rod with acoustic black hole for acoustic emission signal enhancement and its performance.

As an essential auxiliary tool for acoustic emission (AE) detection, waveguide rods are widely used in testing situations where sensors cannot contact the specimens directly, such as high temperature, cryogenic, corrosion, radiation, etc. However, the AE signal attenuation in waveguide rod makes the risk of missing weak acoustic emission events in damage detection, which limits the application of waveguide rods. Therefore, in this work, a novel waveguide rod was presented based on acoustic black hole (ABH) theory to enhance the AE signal before reaching the sensor through the energy convergence effect of the ABH. Firstly, the geometric configuration of the waveguide rod with ABH was designed. The AE signal enhancement effect of the ABH waveguide rod was verified by comparing the amplitude of the AE signal for the traditional waveguide rod and the ABH waveguide rod by the finite element method. Secondly, the influence on the geometric parameters of the ABH waveguide rod for the AE signal enhancement effect was analyzed. The selection method of geometric parameters and the enhancement method of the AE signal with specific frequency bands were proposed to obtain expected AE signal enhancement results. Finally, the pencil-lead breaking experiments were implemented to verify the effectiveness of finite element method and the AE signal enhancement effect of ABH waveguide rod. The results show that the waveguide rod with ABH given in this paper has a significant AE signal enhancement effect and a good application prospect in structural acoustic emission health monitoring.

MicroRNA-1 Deficiency Is a Primary Etiological Factor Disrupting Cardiac Contractility and Electrophysiological Homeostasis.

BACKGROUND: MicroRNA-1 (miR1), encoded by the genes miR1-1 and miR1-2, is the most abundant microRNA in the heart and plays a critical role in heart development and physiology. Dysregulation of miR1 has been associated with various heart diseases, where a significant reduction (>75%) in miR1 expression has been observed in patient hearts with atrial fibrillation or acute myocardial infarction. However, it remains uncertain whether miR1-deficiency acts as a primary etiological factor of cardiac remodeling. METHODS: miR1-1 or miR1-2 knockout mice were crossbred to produce 75%-miR1-knockdown (75%KD; miR1-1+/-:miR1-2-/- or miR1-1-/-:miR1-2+/-) mice. Cardiac pathology of 75%KD cardiomyocytes/hearts was investigated by ECG, patch clamping, optical mapping, transcriptomic, and proteomic assays. RESULTS: In adult 75%KD hearts, the overall miR1 expression was reduced to ≈25% of the normal wild-type level. These adult 75%KD hearts displayed decreased ejection fraction and fractional shortening, prolonged QRS and QT intervals, and high susceptibility to arrhythmias. Adult 75%KD cardiomyocytes exhibited prolonged action potentials with impaired repolarization and excitation-contraction coupling. Comparatively, 75%KD cardiomyocytes showcased reduced Na+ current and transient outward potassium current, coupled with elevated L-type Ca2+ current, as opposed to wild-type cells. RNA sequencing and proteomics assays indicated negative regulation of cardiac muscle contraction and ion channel activities, along with a positive enrichment of smooth muscle contraction genes in 75%KD cardiomyocytes/hearts. miR1 deficiency led to dysregulation of a wide gene network, with miR1's RNA interference-direct targets influencing many indirectly regulated genes. Furthermore, after 6 weeks of bi-weekly intravenous tail-vein injection of miR1 mimics, the ejection fraction and fractional shortening of 75%KD hearts showed significant improvement but remained susceptible to arrhythmias. CONCLUSIONS: miR1 deficiency acts as a primary etiological factor in inducing cardiac remodeling via disrupting heart regulatory homeostasis. Achieving stable and appropriate microRNA expression levels in the heart is critical for effective microRNA-based therapy in cardiovascular diseases.

A soft, bioinspired artificial lymphatic system for interactive ascites transfer.

Low-flow removal of refractory ascites is critical to treating cirrhosis and digestive system tumor, and thus, commercial ascites pump emerged lately. The rigid structure of clinically available pumps rises complication rate and lack of flow rate monitoring hinders early warning of abnormalities. Herein, a soft artificial system was proposed inspired by lymph for interactive ascites transfer with great biocompatibility. The implantable system is composed of pump cavity, valves and tubes, which are soft and flexible made by silica gel. Therefore, the system possesses similar modulus to tissues and can naturally fit surrounding tissues. The cavity with magnetic tablet embedded is driven by extracorporeal magnetic field. Subsequently, the system can drain ascites with a top speed of 23 mL min-1, much higher than that of natural lymphatic system and state-of-art devices. Moreover, integrated flexible sensors enable wireless, real-time flow rate monitoring, serving as proof of treatment adjustment, detection and locating of malfunction at early stage. The liver function of experimental objects was improved, and no severe complications occurred for 4 weeks, which proved its safety and benefit to treatment. This artificial lymphatic system can serve as a bridge to recovery and pave the way for further clinical research.

M1 polarization of chicken macrophage HD11 can be activated by duck Tembusu virus via MyD88-NF-κB-mediated signaling pathway.

Duck Tembusu virus (DTMUV) has caused significant economic losses to the global duck industry since its outbreak in 2010. The macrophages act as the key immune cell, and its polarization in different functional states is very important for host's immune responses and microbial infections. Avian macrophages are the main target cells of DTMUV, its polarization induced by DTMUV and the underlying mechanisms were explored in this study. Through quantitative real-time PCR, nitrite assay, and flow cytometry analysis, we found that DTMUV caused severe inflammatory responses in chicken macrophage line HD11 by reprogramming the expression of M1- and M2-associated genes, leading to the polarization of HD11 macrophage to M1-type. In term of mechanism, transcriptomics was performed to analyze the M1-type polarization triggered by DTMUV, it was found that most differential genes were implicated in biological processes, and DTMUV infection significantly activated innate immune signaling pathways, including cytokine-cytokine receptor interaction, MAPK signaling pathway. Moreover, transcription factors NF-κB and AP1 also be activated after viral infection. However, further validation analysis by inhibitors and siRNAs of NF-κB and AP1 showed that NF-κB molecule was essential for DTMUV-induced M1 polarization in HD11 cell, but not AP1. Additionally, the inhibiting assays targeting MyD88 and TRIF molecules were conducted to determine their effect on NF-κB and M1-associated genes upregulated by DTMUV. The results showed that although the inhibition of both MyD88 and TRIF significantly downregulated the mRNA level of NF-κB, but the expression of M1-associated genes such as CD86 was lower in MyD88 inhibition group than in the other group, indicating that the role of MyD88 in mediating M1 polarization induced by DTMUV was more important. Overall, these results demonstrated that DTMUV infection induces M1-type polarization in chicken macrophage HD11 through MyD88-NF-κB signaling pathways. This finding will lay the foundation for further study the pathogenesis of DTMUV, and provide new insights into the prevention and control of this disease.

Experience in managing splenic hilar vascular injury during laparoscopic total gastrectomy.

Splenic hilar vascular injury may occur during laparoscopic radical total gastrectomy for splenic hilar lymph node dissection and often causes massive hemorrhage, requiring conversion to laparotomy and splenectomy. Surgeons treating splenic hilar vascular injuries need a way to stop bleeding promptly and accurately. Herein, we report a case of splenic hilar vascular injury during laparoscopic total gastrectomy in which we successfully managed to stop the bleeding and preserve the spleen.

Identification of cuticular protein genes and analysis of their roles in phosphine resistance of the rusty grain beetle Cryptolestes ferrugineus.

The rusty grain beetle, Cryptolestes ferrugineus (Stephens) is one of the most economically important stored grain pests, and it has evolved the high resistance to phosphine. Cuticular proteins (CPs) are the major structural components of insect cuticle, and previous studies have confirmed that CPs were involved in insecticide resistance. However, the CPs of C. ferrugineus are still poorly characterized, and thus we conducted transcriptome-wide identification of CP genes and analyze their possible relationships with phosphine resistance in this pest. In this study, a total of 122 putative CPs were annotated in the C. ferrugineus transcriptome data by blasting with the known CPs of Tribolium castaneum. The analysis of conserved motifs revealed these CPs of C. ferrugineus belonging to 9 different families, including 87 CPR, 13 CPAP1, 7 CPAP3, 3 Tweedle, 1 CPLCA, 1 CPLCG, 5 CPLCP, 2 CPCFC, and 3 CPFL proteins. The further phylogenetic analysis showed the different evolutionary patterns of CPs. Namely, we found some CPs (CPR family) formed species-specific protein clusters, indicating these CPs might occur independently among insect taxa, and while some other CPs (CPAP1 and CPAP3 family) shared a closer correlation based on the architecture of protein domains. Subsequently, the previous RNA-seq data were applied to establish the expression profiles of CPs in a phosphine susceptible and resistant populations of C. ferrugineus, and a large amount of CP genes were found to be over-expressed in resistant insects. Lastly, an up-regulated CP gene (CPR family) was selected for the further functional analysis, and after this gene was silenced via RNA interference (RNAi), the sensitivity to phosphine was significantly enhanced in C. ferrugineus. In conclusion, the present results provided us an overview of C. ferrugineus CPs, and which suggested that the CPs might play the critical roles in phosphine resistance.

Increased expression of LINC00323 correlates with tumor progression and poor prognosis of gastric cancer.

BACKGROUD/AIMS: LINC00323 is a novel lncRNA which has reported to play an important role in the development and recurrence in several cancers. However, the expression and predictive value of LINC00323 in gastric cancer (GC) remain mysterious. METHODS: LINC00323 expression in GC tissues and adjacent normal tissues was evaluated by quantitative reverse-transcription PCR (qRT-PCR). The relationship between LINC00323 expression and clinicopathological features and patients' survival were analyzed. Univariate and multivariate survival analyses were performed. RESULTS: LINC00323 expression were found to be significantly increased in GC tissues. High expression of LINC00323 exerted a pro-tumor effect in the late stage of GC development. Kaplan-Meier analysis showed that patients with high LINC00323 were associated with poor overall survival (OS) and progression-free survival (PFS). Moreover, the combination of TNM stage and drinking status better identified GC patient outcome than those of TNM stage alone. CONCLUSIONS: Our data showed that LINC00323 overexpression might serve as a novel independent prognostic factor for survival of GC patients, suggesting LINC00323 was a potential biomarker and therapeutic target for GC.

Regio- and diastereoselective synthesis of diverse spirocyclic indenes by cyclization with indene-dienes as two carbon building blocks.

We report a base-promoted cyclization with indene-dienes as two carbon building blocks toward diverse spirocyclic indene scaffolds including hexacyclic spiroindenes bearing benzo pyran motifs and pentacyclic spiroindenes containing oxindole units in high yields with excellent diastereoselectivities.

Mesenchymal stem cells-derived IL-6 promotes invasion and metastasis of oral squamous cell carcinoma via JAK-STAT3 signalling.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is often diagnosed with cervical lymph node metastasis. Mesenchymal stem cells (MSCs) and interleukin-6 (IL-6) signalling are considered to play important roles in promoting tumour malignancy. The detailed biological interaction of MSCs and IL-6 and the subsequent effect on OSCC metastasis remain largely unclear. This study aimed to determine the effects and molecular mechanism of MSCs-derived IL-6 on tumour invasion and metastasis. SUBJECTS AND METHODS: The effects of MSC-derived IL-6 and tocilizumab on the proliferation, mobility, and epithelial-mesenchymal transition (EMT) of OSCC cells and potential pathways were detected in vitro. In addition, a murine xenograft model was generated to verify the biological mechanism in vivo. RESULTS: The results showed that the expression of MSCs and EMT-related signals was increased in poorly differentiated OSCC tissues. MSCs released a higher level of IL-6 and promoted the proliferation, invasion, and metastasis of OSCC cells and solid neoplasms, which were activated by the downstream molecules JAK and STAT3. CONCLUSIONS: The results indicated that MSCs-derived IL-6-promoted tumour invasion and metastasis via JAK-STAT3 signalling. Blockade of this pathway by tocilizumab may be a potential treatment to improve the prognosis and survival rate of patients with OSCC.

A regioselective [3 + 2] cycloaddition reaction of 2-benzylidene-1-indenones with functional olefins to access indanone-fused 2D/3D skeletons.

The regioselective [3 + 2] cycloaddition reaction of 2-benzylidene-1-indenones with functional olefins was established with DABCO as a base under mild conditions. Using this approach, a series of diversely substituted indanone-fused cyclopentane polycycles with highly crowded multiple substituents were synthesized in high yields.

Single-cell analysis of peripheral blood from high-altitude pulmonary hypertension patients identifies a distinct monocyte phenotype.

Immune and inflammatory responses have an important function in the pathophysiology of pulmonary hypertension (PH). However, little is known about the immune landscape in peripheral circulation in patients with high-altitude pulmonary hypertension (HAPH). We apply single-cell transcriptomics to characterize the monocytes that are significantly enriched in the peripheral blood mononuclear cells (PBMC) of HAPH patients. We discover an increase in C1 (non-classical) and C2 (intermediate) monocytes in PBMCs and a decrease in hypoxia-inducible transcription factor-1α (HIF-1α) in all monocyte subsets associated with HAPH. In addition, we demonstrate that similar immune adaptations may exist in HAPH and PH. Overall, we characterize an immune cell atlas of the peripheral blood in HAPH patients. Our data provide evidence that specific monocyte subsets and HIF-1α downregulation might be implicated in the pathogenesis of HAPH.

Specific and Long-Term Luminescent Monitoring of Hydrogen Peroxide in Tumor Metastasis.

Luminescent monitoring of endogenous hydrogen peroxide (H2 O2 ) in tumors is conducive to understanding metastasis and developing novel therapeutics. The clinical transformation is obstructed by the limited light penetration depth, toxicity of nano-probes, and lack of long-term monitoring modes of up to days or months. New monitoring modes are introduced via specific probes and implantable devices, which can achieve real-time monitoring with a readout frequency of 0.01 s or long-term monitoring for months to years. Near-infrared dye-sensitized upconversion nanoparticles (UCNPs) are fabricated as the luminescent probes, and the specificity to reactive oxygen species is subtly regulated by the self-assembled monolayers on the surfaces of UCNPs. Combined with the passive implanted system, a 20-day monitoring of H2 O2 in the rat model of ovarian cancer with peritoneal metastasis is achieved, in which the limited light penetration depth and toxicity of nano-probes are circumvented. The developed monitoring modes show great potential in accelerating the clinical transformation of nano-probes and biochemical detection methods.

Kazinol B protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced cardiac injury by modulating the AKT/AMPK/Nrf2 signalling pathway.

CONTEXT: Kazinol B (KB), an isoprenylated flavan derived from Broussonetia kazinoki Sieb. (Moraceae) root, has long been used in folk medicine. OBJECTIVE: This study examines the protective effects of KB and its underlying mechanisms in hypoxia and reoxygenation (H/R)-induced cardiac injury in H9c2 rat cardiac myoblasts. MATERIALS AND METHODS: H9c2 cells were incubated with various concentrations of KB (0, 0.3, 1, 3, 10 and 30 µM) for 2 h and then subjected to H/R insults. The protective effects of KB and its underlying mechanisms were explored. RESULTS: KB significantly elevated cell viability (1 µM, 1.21-fold; 3 µM, 1.36-fold, and 10 µM, 1.47-fold) and suppressed LDH release (1 µM, 0.77-fold; 3 µM, 0.68-fold, and 10 µM, 0.59-fold) in H/R-induced H9c2 cells. Further, 10 µM KB blocked apoptotic cascades, as shown by the Annexin-V/PI (0.41-fold), DNA fragmentation (0.51-fold), caspase-3 (0.52-fold), PARP activation (0.27-fold) and Bax/Bcl-2 expression (0.28-fold) assays. KB (10 µM) downregulated reactive oxygen species production (0.51-fold) and lipid peroxidation (0.48-fold); it upregulated the activities of GSH-Px (2.08-fold) and SOD (1.72-fold). KB (10 µM) induced Nrf2 nuclear accumulation (1.94-fold) and increased ARE promoter activity (2.15-fold), HO-1 expression (3.07-fold), AKT (3.07-fold) and AMPK (3.07-fold) phosphorylation. Nrf2 knockdown via using Nrf2 siRNA abrogated KB-mediated protective effects against H/R insults. Moreover, pharmacological inhibitors of AKT and AMPK also abrogated KB-induced Nrf2 activation and its protective function. DISCUSSION AND CONCLUSIONS: KB prevented H/R-induced cardiomyocyte injury via modulating the AKT and AMPK-mediated Nrf2 induction. KB might be a promising drug candidate for managing ischemic cardiac disorders.

The insulin long-acting chitosan - Polyethyleneimine nanoparticles to treat the type 2 diabetes mellitus and prevent the associated complications.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, which is ultimately treated by the insulin (INS). However, the subcutaneous (s. c.) injection of insulin solution faces the problems of pain and unsatisfactory patient compliance. In this study, the long-acting formulations of insulin are propsed to treat the T2DM and prevent the associated complications. The chitosan (CS) and/or branched polyethyleneimine (bPEI) nanoparticles (bPEI-INS NPs, CS-bPEI-INS NPs) were constructed to load insulin. The long -acting nanoparticles successfully achieved the sustained release of the INS in vitro and in vivo. After s. c. administration, the CS-bPEI-INS NPs greatly improved the INS bioavailability. As a result, the CS-bPEI-INS NPs produced sustained glucose-lowering effects, promising short-term and long-term hypoglycemic efficacy in the T2DM model. Furthermore, the treatment of the CS-bPEI-INS NPs greatly protected the islet in the pancreas and prevented the associated complications of the T2DM, such as cardiac fibrosis in the myocardial interstitium and the perivascular area. In a word, the CS-bPEI-INS NPs was an encouraging long-acting formulation of insulin and had great potential in the treatment of T2DM.

Activatable unsaturated liposomes increase lipid peroxide of cell membrane and inhibit tumor growth.

The cancer chemodynamic therapy based on the Fenton reaction has been attracting more and more attention. However, the performance of the Fenton reaction is restricted by the unsuitable physiological pH value and inadequate H2O2 content in the tumor microenvironment (TME). In this study, we proposed a novel method of inducing lipid peroxide (LPO) of the cancer cell membrane, whose performance is not limited by the pH value and H2O2 in the TME. The activatable LPO-inducing liposomes were constructed by encapsulating Fe3+-containing compound ferric ammonium citrate (FC) in the unsaturated soybean phospholipids (SPC). It was found that the FC could be reduced by the overexpressed glutathione (GSH) in the TME and produce iron redox couple. The Fe3+/Fe2+ mediated the peroxidation of the unsaturated SPC and induced the LPO in the cancer cells. Finally, LPO accumulation led to cancer cell death and tumor growth inhibition. Furthermore, the activatable liposomes did not damage healthy tissues because of the low GSH content in normal tissues and the GSH-triggered activation of the nanocarrier. Together, our findings revealed that FC-SPC-lipo displayed excellent anti-tumor performance and its therapeutic effects are less influenced by the TME, compared with the traditional ferroptosis.

Effect of Stacking Sequence on Fatigue Performance of CFRP-Al Single-Lap Adhesive Joints: Experimental Study.

This study aimed to explore failure mechanisms of carbon fibre-reinforced plastic (CFRP)-aluminium (Al) single-lap adhesive joints which CFRP adherends had different stacking sequences. These results showed that fatigue performance of CFRP decreased as the number of 45° plies increased, which caused the initial failure location to gradually move from the adhesive layer towards the CFRP. Under high load levels, joint-failure models were influenced by the stacking sequence of CFRP; large-area cohesive failure occurred in joints when the CFRP stacking sequence was [0/90]4s and [0/45/-45/90]2s, and delamination failure occurred when the CFRP stacking sequence was [45/-45]4s, due to the weak interlaminar properties of CFRP. However, under low load levels, the stacking sequence of CFRP had little effect on the failure model of the joint, with interfacial failure being the main failure mode for all joints due to weakening of the mechanical interlock.