Plumbagin ameliorates LPS-induced acute lung injury by regulating PI3K/AKT/mTOR and Keap1-Nrf2/HO-1 signalling pathways.

Acute lung injury (ALI) is a major pathophysiological problem characterized by severe inflammation, resulting in high morbidity and mortality. Plumbagin (PL), a major bioactive constituent extracted from the traditional Chinese herb Plumbago zeylanica, has been shown to possess anti-inflammatory and antioxidant pharmacological activities. However, its protective effect on ALI has not been extensively studied. The objective of this study was to investigate the protective effect of PL against ALI induced by LPS and to elucidate its possible mechanisms both in vivo and in vitro. PL treatment significantly inhibited pathological injury, MPO activity, and the wet/dry ratio in lung tissues, and decreased the levels of inflammatory cells and inflammatory cytokines TNF-α, IL-1ß, IL-6 in BALF induced by LPS. In addition, PL inhibited the activation of the PI3K/AKT/mTOR signalling pathway, increased the activity of antioxidant enzymes CAT, SOD, GSH and activated the Keap1/Nrf2/HO-1 signalling pathway during ALI induced by LPS. To further assess the association between the inhibitory effects of PL on ALI and the PI3K/AKT/mTOR and Keap1/Nrf2/HO-1 signalling, we pretreated RAW264.7 cells with 740Y-P and ML385. The results showed that the activation of PI3K/AKT/mTOR signalling reversed the protective effect of PL on inflammatory response induced by LPS. Moreover, the inhibitory effects of PL on the production of inflammatory cytokines induced by LPS also inhibited by downregulating Keap1/Nrf2/HO-1 signalling. In conclusion, the results indicate that the PL ameliorate LPS-induced ALI by regulating the PI3K/AKT/mTOR and Keap1-Nrf2/HO-1 signalling, which may provide a novel therapeutic perspective for PL in inhibiting ALI.

TGFB1 stimulates the proliferation of quiescent oogonial stem cells in chicken.

In brief: Oogonial stem cells in the adult ovary can generate oocytes, but they are usually quiescent. TGFB1 is key in stimulating the proliferation of OSC, thereby ensuring the sustained reproductive potential in poultry species. Abstract: Oogonial stem cells (OSCs) are a type of germ stem cell present in the adult ovary. They have the ability to self-renew through mitosis and differentiate into oocytes through meiosis. We have previously identified a population of OSCs in the chicken ovary, but the underlying mechanisms controlling their activation and proliferation were unclear. In this study, we observed that OSCs showed robust proliferation when cultured on a layer of chicken embryo fibroblasts (CEF), suggesting that CEF may secrete certain crucial factors that activate OSC proliferation. We further detected TGFB1 as a potent signaling molecule to promote OSC proliferation. Additionally, we revealed the signaling pathways that play important roles downstream of TGFB1-induced OSC proliferation. These findings provide insights into the mechanisms underlying OSC proliferation in chickens and offer a foundation for future research on in situ activation of OSC proliferation in ovary and improvement of egg-laying performance in chickens.

Comprehensive evaluation of vaginal intraepithelial neoplasia development after hysterectomy: insights into diagnosis and treatment strategies.

Vaginal intraepithelial neoplasia (VaIN), a precancerous lesion associated with human papillomavirus (HPV), impacts women's health and quality of life. However, the natural progression of VaIN after hysterectomy remains uncertain, due to its low incidence. The existing literature predominantly consists of single-center retrospective studies lacking robust evidence-based medicine. The management of VaIN after hysterectomy is diverse and controversial, lacking a consensus on the optimal approach. Therefore, it is imperative to investigate the development of VaIN after hysterectomy, emphasizing the importance of accurate diagnosis and effective management strategies.

Broadband SnS/Te photodetector to long-wavelength infrared: breaking the spectrum limit through alloy engineering.

Materials based on group IV chalcogenides, are considered to be one of the most promising materials for high-performance, broadband photodetectors due to their wide bandgap coverage, intriguing chemical bonding and excellent physical properties. However, the reported photodetectors based on SnS are still worked at relatively narrow near-infrared band (as far as 1550 nm) hampered by the nonnegligible bandgap of 1.1-1.5 eV. Here, a novel photodetector based on Te alloyed SnS thin film was demonstrated with an ultra-broadband response up to 10.6 µm. By controlling the Te alloyed concentration in SnS increasing to 37.64%, the bandgap narrows to 0.23 eV, exhibiting a photoresponse potential at long-wavelength infrared excitation. Our results show Te-alloying can remarkably enhance the detection properties of SnS/Te photodetectors. The photoresponsivity and detectivity of 1.59 mA/W and 2.3 × 108 Jones were realized at 10.6 µm at room temperature. Moreover, the nonzero photogain was observed generated by nonlinearly increased photocurrent density, resulting in a superlinear dependency between photoresponsivity and light intensity. Our studies successfully broaden photoresponse spectrum of SnS toward the mid-infrared range for the first time. It also suggests that alloying is an effective technique for tuning the band edges of group IV chalcogenides, contributing deep implications for developing future optoelectronic applications.

Strong, anisotropic, layer-independent second harmonic generation in multilayer SnS film.

Materials based on group IV chalcogenides exhibit extensive technologically important properties. Its unusual chemical bonding and off-centering of in-layer sublattices could cause chemical polarity and weakly broken symmetry, making optical field controlling feasible. Here, we fabricated large-area SnS multilayer films and observed unexpected strong SHG response at 1030 nm. The appreciable SHG intensities were obtained with an independence on layer, which is opposite to the generation principle of overall nonzero dipole moment only in odd-layer material. Taking GaAs for reference, the second-order susceptibility was estimated to be 7.25 pm/V enhanced by mixed-chemical bonding polarity. Further polarization-dependent SHG intensity confirmed the crystalline orientation of SnS films. The results imply surface inversion symmetry broken and nonzero polarization field modified by metavalent bonding should be the origin of SHG responses. Our observations establish multilayer SnS as a promising nonlinear material, and will guide in design of IV chalcogenides with improved optics and photonics properties for the potential applications.

Hardness and superconductivity in tetragonal LiB4 and NaB4.

Boron-based compounds have triggered substantial attention due to their multifunctional properties, incorporating excellent hardness and superconductivity. While tetragonal metal borides LiB4 and NaB4 with BaAl4-type structure and striking clathrate boron motif have been induced under compression, there is still a lack of deep understanding of their potential properties at ambient pressure. We herein conduct a comprehensive study on I4/mmm-structured LiB4 and NaB4 under ambient pressure via first-principles calculations. Remarkably, both LiB4 and NaB4 are found to possess high Vickers hardness of 39 GPa, which is ascribed to the robust boron framework with strong covalency. Furthermore, their high hardness values together with distinguished stability make them highly potential superhard materials. Meanwhile, electron-phonon coupling analysis reveals that both LiB4 and NaB4 are conventional phonon-mediated superconductors, with critical temperatures of 6 and 8 K at 1 atmosphere pressure (atm), respectively, mainly arising from the coupling of B 2p electronic states and the low-frequency phonon modes associated with Li-, Na-, and B-derived vibrations. This work provides valuable insights into the mechanical and superconducting behaviors of metal borides and will boost further studies of emergent borides with multiple functionalities.

The Selective Trigeminal Nerve Motor Branching Transfer: an Preliminary Clinical Application for Facial Reanimation.

OBJECTIVE: To investigate the effectiveness and feasibility of selective trigeminal nerve motor branching in the repair of facial palsy. MATERIALS AND METHODS: The clinical data of patients with advanced facial palsy from 2016 to 2021 were retrospectively analyzed, including pictures and videos before and 18 months after surgery. The House-Brackmann grading system was used to evaluate facial nerve function before and after repair, and the symmetry scale of oral commissure at rest and Terzis' smile functional evaluation scale were used to qualitatively assess the symmetry of the mouth angle and smile function. The distance of oral commissure movement was assessed to evaluate the dynamic repair effect, and the FaCE facial muscle function scale was used to assess patients' subjective perception before and after surgery. RESULTS: A total of four patients were included in the study, all of whom showed signs of recovery of facial nerve function within six months. In all four cases, significant improvements were observed in House-Brackmann ratings, the smile function score and the symmetry scale of oral commissure at rest. Compared to the pre-operative period, the four patients demonstrated various degrees of eye-closing function recovery, and a significant improvement in oral commissure movement was observed ( P <0.001). FaCE scores also improved significantly after surgery ( P =0.019). CONCLUSION: Concurrent selective facial nerve repair with trigeminal branch-facial nerve anastomosis resulted in eye-closing function recovery while improving static and dynamic symmetry, yielding acceptable postoperative results.

New biopsy after antibiotic treatment: effect on outcomes of assisted reproduction in patients with infertility and chronic endometritis.

RESEARCH QUESTION: What is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes? DESIGN: Infertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared. RESULTS: No significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates. CONCLUSIONS: Endometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field.

A circular RNAs dataset landscape reveals potential signatures for the detection and prognosis of early-stage lung adenocarcinoma.

BACKGROUND: This study aimed to identify potential circular ribonucleic acid (circRNA) signatures involved in the pathogenesis of early-stage lung adenocarcinoma (LAC). METHODS: The circRNA sequencing dataset of early-stage LAC was downloaded from the Gene Expression Omnibus database. First, the differentially expressed circRNAs (DEcircRNAs) between tumour and non-tumour tissues were screened. Then, the corresponding miRNAs and their target genes were predicted. In addition, prognosis-related genes were identified using survival analysis and further used to build a network of competitive endogenous RNAs (ceRNAs; DEcircRNA-miRNA-mRNA). Finally, the functional analysis and drug-gene interaction analysis of mRNAs in the ceRNA network was performed. RESULTS: A total of 35 DEcircRNAs (30 up-regulated and 5 down-regulated circRNAs) were identified. Moreover, 135 DEcircRNA-miRNA and 674 miRNA-mRNA pairs were predicted. The survival analysis of these target mRNAs revealed that 60 genes were significantly associated with survival outcomes in early-stage LAC. Of these, high levels of PSMA 5 and low levels of NAMPT, CPT 2 and TNFSF11 exhibited favourable prognoses. In addition, the DEcircRNA-miRNA-mRNA network was constructed, containing 5 miRNA-circRNA (hsa_circ_0092283/hsa-miR-762/hsa-miR-4685-5p; hsa_circ_0070610/hsa-let-7a-2-3p/hsa-miR-3622a-3p; hsa_circ_0062682/hsa-miR-4268) and 60 miRNA-mRNA pairs. Functional analysis of the genes in the ceRNA network showed that they were primarily enriched in the Wnt signalling pathway. Moreover, PSMA 5, NAMPT, CPT 2 and TNFSF11 had strong correlations with different drugs. CONCLUSION: Three circRNAs (hsa_circ_0062682, hsa_circ_0092283 and hsa_circ_0070610) might be potential novel targets for the diagnosis of early-stage LAC.

[Pharmacology of combination of disease and syndrome:strategies and methods of pharmacology of Chinese medicine].

The pharmacology of Chinese medicine is an academic discipline that studies the interaction between Chinese medicine and organism(including pathogens) by modern science and technology under the guidance of traditional Chinese medicine(TCM) theories. However, the pharmacology of Chinese medicine is mainly guided by the theories, techniques, and methods of modern medicine in the development, and TCM theories have been ignored to a certain extent, which does not conform to the action characteristics of Chinese medicine in essence. Since systematic research ideas, strategies, methods, and technologies that conform to the characteristics of TCM have not been established, it is unable to reveal the scientific connotation of TCM in the prevention and treatment of diseases. Therefore, according to the trend of the modern development of TCM and the research status of pharmacology of Chinese medicine, this study put forward the concept of pharmacology of combination of disease and syndrome and expounded the relevant background, content, methods, and significance of this concept. It is expected to improve the standardization of pharmacology of combination of disease and syndrome, guide the safe medication, provide new references for the scientific development of pharmacology of Chinese medicine, and promote the development of the modernization of Chinese medicine.

Butenolide Derivatives of Biobased Furans: Sustainable Synthetic Dyes.

The dye and pigment manufacturing industry is one of the most polluting in the world. Each year, over one million tons of petrochemical colorants are produced globally, the synthesis of which generates a large amount of waste. Naturally occurring, plant-based dyes, on the other hand, are resource intensive to produce (land, water, energy), and are generally less effective as colorants. Between these two extremes would be synthetic dyes that are fully sourced from biomass-derived intermediates. The present work describes the synthesis of such compounds, containing strong chromophores that lead to bright colors in the yellow to red region of the visible spectrum. The study was originally motivated by an early report of an unidentified halomethylfurfural derivative which resulted from hydrolysis in the presence of barium carbonate, now characterized as a butenolide of 5-(hydroxymethyl)furfural (HMF). The method has been generalized for the synthesis of dyes from other biobased platform molecules, and a mechanism is proposed.

Functional analysis of novel RUNX2 mutations in cleidocranial dysplasia.

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal disorder caused by mutation of runt-related transcription factor 2 (RUNX2) gene. The purpose of this study was to explore novel RUNX2 mutations in seven individuals with CCD and investigate the function of the mutant RUNX2 proteins. DNA samples were prepared from the peripheral blood of the CCD individuals, and then subjected to DNA sequencing. Conservation and secondary structure analysis were performed based on RUNX2 sequencing results. pEGFP-C1 plasmids containing GFP-tagged wild-type RUNX2 and three novel RUNX2 mutations expression cassettes were constructed, and then transfected into HEK293T cells. Cell fluorescence, luciferase assay and western blotting were used to analyse the subcellular distribution and function of the mutant RUNX2 proteins. Three novel mutations (R193G, 258fs, Y400X) were found in the seven CCD patients. Conservation and structure analysis show one novel mutation (R193G) in Runt domain and two novel mutations (258fs and Y400X) in PST domain of RUNX2. Western blotting confirmed that the 258fs and Y400X mutations produced truncated proteins. Fluorescence detection showed that the three novel mutants localised exclusively in the nucleus. However, luciferase assay indicated all mutants severely impaired the transactivation activities of RUNX2 on osteocalcin promoter. Our results broaden the spectrum of RUNX2 mutations in CCD individuals and demonstrated that loss of function in RUNX2 is responsible for CCD.

Restorative treatment strategies for patients with cleidocranial dysplasia.

OBJECTIVE: To develop a suitable treatment strategy for patients with cleidocranial dysplasia (CCD) who miss the optimal early treatment stage. MATERIALS AND METHODS: This study enrolled 15 patients with CCD who had all missed the optimal treatment stage and were diagnosed with CCD through clinical examinations and genetic tests. Based on the chief complaints and requirements of the patients, three different therapeutic schedules were devised for these patients. Schedules I (periodontal and endodontic treatments) and II (periodontal, endodontic and prosthodontic treatments) were used for patients with low requirements, whereas Schedule III (multidisciplinary strategy, including periodontal, endodontic, surgical, orthodontic and prosthodontic treatments) was used for patients with high requirements. RESULTS: Schedules I, II and III were used in five, seven and three patients, respectively. Schedule III treatments produced the best outcomes in terms of occlusion and esthetics. CONCLUSIONS: Schedule III based on a comprehensive multidisciplinary therapy is an ideal restorative therapeutic strategy and can achieve good outcomes for patients with CCD who missed the optimal treatment stage.

A disulfidptosis-related lncRNAs cluster to forecast the prognosis and immune landscapes of ovarian cancer.

Objective: Disulfidptosis is a newly recognized form of regulated cell death that has been linked to cancer progression and prognosis. Despite this association, the prognostic significance, immunological characteristics and treatment response of disulfidptosis-related lncRNAs (DRLs) in ovarian cancer have not yet been elucidated. Methods: The lncRNA data and clinical information for ovarian cancer and normal samples were obtained from the UCSC XENA. Differential expression analysis and Pearson analysis were utilized to identify core DRLs, followed by LASSO algorithm. Random Survival Forest was used to construct a prognostic model. The relationships between risk scores, RNA methylation, immune cell infiltration, mutation, responses to immunotherapy and drug sensitivity analysis were further examined. Additionally, qRT-PCR experiments were conducted to validate the expression of the core DRLs in human ovarian cancer cells and normal ovarian cells and the scRNA-seq data of the core DRLs were obtained from the GEO dataset, available in the TISCH database. Results: A total of 8 core DRLs were obtained to construct a prognostic model for ovarian cancer, categorizing all patients into low-risk and high-risk groups using an optimal cutoff value. The AUC values for 1-year, 3-year and 5-year OS in the TCGA cohort were 0.785, 0.810 and 0.863 respectively, proving a strong predictive capability of the model. The model revealed the high-risk group patients exhibited lower overall survival rates, higher TIDE scores and lower TMB levels compared to the low-risk group. Variations in immune cell infiltration and responses to therapeutic drugs were observed between the high-risk and low-risk groups. Besides, our study verified the correlations between the DRLs and RNA methylation. Additionally, qRT-PCR experiments and single-cell RNA sequencing data analysis were conducted to confirm the significance of the core DRLs at both cellular and scRNA-seq levels. Conclusion: We constructed a reliable and novel prognostic model with a DRLs cluster for ovarian cancer, providing a foundation for further researches in the management of this disease.

Mining core information by evaluating semantic importance for unpaired image captioning.

Recently, exciting progress has been made in the research of supervised image captioning. However, manually annotated image-annotation pair data is difficult and expensive to obtain. Therefore, unpaired image captioning becomes an emerging challenge. This paper proposes a method called Mining Core Information by Evaluating Semantic Importance (MCIESI) for Unpaired Image Captioning, which is a method for image captioning using unpaired images and sentences. The main difference from the existing methods is that MCIESI focuses on mining the information that should be described in the image and embodies them in the generated natural language that conforms to human thinking. To achieve this goal, we use scene graphs to represent the semantics of images and evaluates the importance of objects and interaction relationships to mine core information in images, which are then encouraged to be embodied in generated sentences through semantic constraint. Combined with grammatical constraint using adversarial training with real sentence corpus and relative constraint using a triplet loss, the generator is trained to generate semantically plausible and grammatically correct sentences. Extensive experiments verify the effectiveness of MCIESI.

Perillaldehyde ameliorates lipopolysaccharide-induced acute lung injury via suppressing the cGAS/STING signaling pathway.

Acute lung injury (ALI) is a common life-threatening illness characterized by a lung inflammatory response and oxidative stress, and effective agent therapies are currently lacking. mtDNA can be recognized by cGAS/STING, the dysregulation of which leads to inflammatory diseases, such as ALI. Perillaldehyde(PAH), one of the major active components of traditional Chinese medicine made from Perilla frutescens, has antioxidant and antiinflammatory effects. The aim of this study was to explore whether PAH can protect against lipopolysaccharide (LPS)-induced ALI and whether its protective effect is exerted through the regulation of cGAS/STING signaling. We found that PAH significantly inhibited lung histological changes, inflammatory cell infiltration, and the overproduction of inflammatory cytokines induced by LPS. Moreover, PAH inhibited LPS-induced oxidative stress, as shown by the deceases in superoxide dismutase (SOD) and glutathione(GSH) levels and increased in malondialdehyde (MDA) and lactate dehydrogenase (LDH) levels. In addition, PAH markedly downregulated the expression of cGAS, STING, p-TBK, p-IRF3, p-P65, and p-IκB, and pharmacological inhibition of cGAS/STING inhibited ALI- induced by LPS. Furthermore, the levels of mitochondrial ROS (mROS) and mtDNA were increased, and cGAS/STING-mediated IRF3/NF-κB signaling was activated during the inflammatory response- induced by LPS in RAW264.7 cells. In addition, pretreatment with the STING activator partially abolished the inhibitory effect of PAH on the inflammation and activation of STING-mediated IRF3/NF-κB signaling induced by LPS. Overall, the results revealed that PAH can effectively alleviate ALI by inhibiting cGAS/STING-mediated IRF3/NF-κB signaling, and that PAH may be a potential candidate agent for the treatment of ALI.

The Role of Alexithymia and Moral Disengagement in Childhood Physical Abuse and Depressive Symptoms: A Comparative Study Among Rural and Urban Chinese College Students.

Purpose: There is robust evidence indicating the adverse association between childhood abuse and depressive symptoms. However, the ways in which childhood physical abuse is indirectly associated with adulthood depressive symptoms by alexithymia and moral disengagement remain poorly understood, particularly in the context of China. The present study aims to investigate how childhood physical abuse may be associated with depressive symptoms via the serial mediation effects of alexithymia and moral disengagement among college students in China. Methods: A total of 686 college students (female: 53.2%) aged from 17 to 28 years old (M = 21.33; SD = 2.53) were recruited from mainland China to participate in an online survey assessing the variables of interest. Structural equation modeling and multiple group analysis were performed using Mplus 7.0 to investigate the hypothesized model. Results: College students' experiences with childhood physical abuse was significantly associated with their depressive symptoms. This relationship was partially mediated by alexithymia and then by moral disengagement. Meanwhile, alexithymia and moral disengagement had a chain mediating effect on childhood physical abuse and depressive symptoms. Furthermore, multigroup analysis revealed that the association between alexithymia and depressive symptoms was stronger among rural students compared to urban students. Furthermore, the mediation model involving moral disengagement applies exclusively to rural students. Conclusion: Alexithymia and moral disengagement exerted serial mediating effect on the association between childhood physical abuse and depressive symptoms. This pattern was particularly pronounced among rural students. These findings underscore the importance of addressing both childhood adversity and maladaptive cognitive processes in the prevention and treatment of depression.

Solubilization and structural changes of lignin in naked oat stems during subcritical water autohydrolysis.

In this study, the solubilization and structural changes of lignin in naked oat stems were investigated under subcritical water autohydrolysis systems (170-210 °C, 0.68-1.85 MPa). In this system, Hemicellulose was preferentially hydrolyzed in the liquid water at elevated temperatures, leading to the production of acetic acid and glucuronic acid, which acidified the reaction system. Under acidic and high-temperature conditions, lignin primarily underwent degradation and condensation reactions. At autohydrolysis temperatures below 190 °C and autohydrolysis pressures below 1.22 MPa, lignin degradation was predominant, realizing a maximum lignin removal of 47.8 % and breakage of numerous ß-O-4 bonds from lignin. At autohydrolysis temperatures above 190 °C and autohydrolysis pressures above 1.22 MPa, lignin condensation dominated, with an increase in the amount of organic acids generated upon hemicellulose degradation, leading to condensation reactions with the degraded low-molecular-weight lignin. The degree of lignin condensation was positively correlated with the temperature of the reaction system. This study provides essential insights into the dynamic changes in the structure of lignin in both the hydrolysis residue and hydrolysis solution during subcritical water autohydrolysis.