A comprehensive analysis of antibiotic resistance genes in the giant panda gut.

In this study, we have successfully constructed a comprehensive database of metagenome-assembled genomes (MAGs) pertaining to the gut microbiota of the giant panda. Through our analysis, we have identified significant reservoirs of antibiotic resistance genes (ARGs), namely Escherichia coli, Citrobacter portucalensis, and Klebsiella pneumoniae. Furthermore, we have elucidated the primary contributors to ARGs, including Streptococcus alactolyticus and Clostridium SGBP116, in both captive and wild pandas. Additionally, our findings have demonstrated a higher prevalence of ARGs in the metagenome, with notable expression of the RPOB2 gene in S. alactolyticus. Crucially, 1217 ARGs shared homology with human gut ARGs, underscoring the interaction relationship between pandas and human microbiomes. These findings are instrumental in understanding the antibiotic resistance landscape in the giant panda's gut, providing a framework for developing strategies to combat antibiotic resistance and safeguard the health of this endangered species.

An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation.

Alzheimer's disease (AD), the most common form of dementia, has a complex pathogenesis. The number of AD patients has increased in recent years due to population aging, while a trend toward a younger age of onset has arisen, imposing a substantial burden on society and families, and garnering extensive attention. DNA methylation has recently been revealed to play an important role in AD onset and progression. DNA methylation is a critical mechanism regulating gene expression, and alterations in this mechanism dysregulate gene expression and disrupt important pathways, including oxidative stress responses, inflammatory reactions, and protein degradation processes, eventually resulting in disease. Studies have revealed widespread changes in AD patients' DNA methylation in the peripheral blood and brain tissues, affecting multiple signaling pathways and severely impacting neuronal cell and synaptic functions. This review summarizes the role of DNA methylation in the pathogenesis of AD, aiming to provide a theoretical basis for its early prevention and treatment.

High-intensity focused ultrasound for endometrial ablation in adenomyosis: a clinical study.

Objective: The present study aimed to investigate the clinical efficacy of endometrial ablation with high-intensity focused ultrasound (HIFU) for symptom relief in women with adenomyosis. Methods: Between July 2014 and July 2020, 167 patients with adenomyosis treated at the Zhongshan City People's Hospital were enrolled in this study. Patients were divided into two groups according to patient aspirations: the control group, including patients who only underwent ablation of adenomyosis lesions (group A) and the treatment group, including patients who underwent removal of adenomyosis lesions and endometrial ablation (group B). Results: The reduced dysmenorrhea scores (visual analog scale) and menstrual volume scores (pictorial blood assessment chart) were measured before and after treatment. The scores were obtained by subtracting the postoperative scores from the preoperative scores and were compared to determine whether the symptoms had alleviated. Compared with the menstrual volume of group A, that in group B showed significant improvements. The average relief rates of dysmenorrhea in the two groups also showed significant improvement. However, the scores in group B showed a more significant improvement than those in group A. Conclusion: Therefore, our findings suggest that endometrial ablation using HIFU may be superior to conventional therapy with regard to alleviating the symptoms of increased menstruation in women with adenomyosis.

Lymph node targeting strategy using a hydrogel sustained-release system to load effector memory T cells improves the anti-tumor efficacy of anti-PD-1.

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.

Biomimetic MDSCs membrane coated black phosphorus nanosheets system for photothermal therapy/photodynamic therapy synergized chemotherapy of cancer.

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

All-dielectric geometric metasurfaces for the generation and manipulation of perfect high-order Poincaré sphere beams.

A high-order Poincaré sphere (HOPS) can be used to describe high-order modes of waveguides and vector beams, since it generalizes the feature of spin and the orbital angular momentum of light. HOPS beams are such beams with polarization states on the HOPS, which have potential applications in optical manipulation and optical communication. In general, the intensity distribution of this kind of beam changes with the topological charge, which limits their practical applications. Based on the concept of perfect vortex beams (PVBs), perfect HOPS beams have been proposed to solve this problem. Here, a flexible and compact scheme based on all-dielectric metasurfaces for realizing and manipulating perfect HOPS beams at near-infrared wavelength was demonstrated. Geometric-phase-only manipulation was employed for simultaneously controlling the phase and polarization of the incident light. By varying the incident polarization, several selected polarization states on the HOPS could be realized by the proposed metasurface. Further, the single ultra-thin metasurface can also realize high quality multiplexing perfect HOPS beams that carry different topological charges. Finally, a cascaded metasurface system has been proposed for generating and manipulating multiple HOPS beams. This compact flat-optics-based scheme for perfect HOPS beam generation and manipulation demonstrated here can be used for on-chip optical manipulation and integrated optical communication in the future.

Highly sensitive OPD-demodulated fiber temperature sensor based on an ultra-long liquid-core with a syringe shape.

An optical path difference (OPD)-demodulated fiber temperature sensor based on a Fabry-Perot interferometer with a liquid-core is proposed. The length of the liquid-core reaches more than 3 mm, and it shapes like a syringe. It is fabricated by filling cedar oil into a section of the hollow core fiber with two different inner diameters. The cedar oil whose refractive index is larger than that of silica can work as the liquid-core, and its length changes with the temperature variation sensitively owing to the high thermal expansion coefficient (TEC). Theoretical analysis proves that the temperature sensitivity based on the OPD demodulation is proportional to the length of the liquid-core, and the syringe shape can further amplify the sensitivity greatly. The filling length of the cedar oil can be improved greatly by the inside-instilling method through an ultra-fine silica needle. As a result, the OPD sensitivity is as high as 50.93 µm/°C, which is three orders of magnitude higher than that of most reported sensors. Besides, the sensor also offers excellent repeatability and stability owing to the absence of residual stress in the liquid material.

[Mechanism of mitochondrial dysfunction in polycystic ovary syndrome and traditional Chinese medicine intervention: a review].

Polycystic ovary syndrome(PCOS) is a highly prevalent endocrine and reproductive disorder characterized by ovulatory dysfunction, hyperandrogenism(HA), and polycystic ovarian morphology(PCOM). It is often accompanied by insulin resistance(IR), obesity, and metabolic disorders and can lead to cardiovascular diseases, endometrial carcinoma and many other late complications, seriously affecting the physical and mental health and quality of life in premenopausal women. The etiology of PCOS is still unknown and many scholars assume that mitochondrial dysfunction may represent a major pathogenic factor in PCOS in recent years. With a holistic view, treatment based on syndrome differentiation, and multi-system and multi-target treatment manner, traditional Chinese medicine(TCM) can mitigate the symptoms and signs of PCOS from multiple aspects. Although there have been reviews on the mechanism of mitochondrial dysfunction in PCOS, there is still a lack of reviews on the intervention of mitochondrial function by TCM to treat PCOS. Therefore, this paper focuses on the role of mitochondrial dysfunction in PCOS and summarizes the studies about the TCM intervention of PCOS by regulating the mitochondrial function, inflammation, oxidative stress(OS), autophagy, and apoptosis in the last five years, aiming to shed new light on the prevention and treatment of PCOS with TCM.

MicroRNAs in chronic pediatric diseases (Review).

MicroRNAs are small non-coding RNAs with a length of 20-24 nucleotides. They bind to the 3'-untranslated region of target genes to induce the degradation of target mRNAs or inhibit their translation. Therefore, they are involved in the regulation of development, apoptosis, proliferation, differentiation and other biological processes (including hormone secretion, signaling and viral infections). Chronic diseases in children may be difficult to treat and are often associated with malnutrition resulting from a poor diet. Consequently, further complications, disease aggravation and increased treatment costs impose a burden on patients and their families. Existing evidence suggests that microRNAs are involved in various chronic non-neoplastic diseases in children. The present review discusses the roles of microRNAs in five major chronic diseases in children, namely, diabetes mellitus, congenital heart diseases, liver diseases, bronchial asthma and epilepsy, providing a theoretical basis for them to become therapeutic biomarkers in chronic pediatric diseases.

Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy.

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

Is elevated baseline SHBG associated with increased ovulation?

Sexual hormone binding globulin (SHBG) is associated with the endocrine and reproductive systems. We aimed to investigate the role of SHBG in the reproductive process. Therefore, we conducted a secondary analysis of the PCOSAct (Polycystic Ovary Syndrome and Acupuncture Clinical Trial) study, which involved 21 sites in China and a total of 1000 women with PCOS. Out of these, 954 women with SHBG were included in the analysis. Through multivariate analysis of ovulation predictors, we found that age, BMI, estradiol, testosterone, and SHBG all showed a positive predictive value for ovulation (p = 0.0211, 0.0011, 0.0211, 0.0029, 0.0434, respectively). However, the LH to FSH ratio had a negative predictive value (p = 0.0539). Higher quartiles of SHBG were associated with a higher rate of ovulation, and per quartile increased was statistically significant (HR = 1.138, 95%CI [1.054,1.229]). The association remained significant even after adjusting for testosterone (HR = 1.263, 95%CI [1.059, 1.507]). On the other hand, quartiles of testosterone and estradiol did not exhibit any significant tendency toward ovulation. SHBG demonstrated predictive ability for ovulation, conception, pregnancy, and live birth (p < 0.05), and this correlation remained significant after adjusting intervention. Kaplan-Meier curves illustrated that increased levels of SHBG were a factor in high rates of ovulation, conception, and pregnancy. In comparison to other sexual hormones, a higher baseline level of SHBG was related to increased ovulation.

Premature ovarian insufficiency: a review on the role of oxidative stress and the application of antioxidants.

Normal levels of reactive oxygen species (ROS) play an important role in regulating follicular growth, angiogenesis and sex hormone synthesis in ovarian tissue. When the balance between ROS and antioxidants is disrupted, however, it can cause serious consequences of oxidative stress (OS), and the quantity and quality of oocytes will decline. Therefore, this review discusses the interrelationship between OS and premature ovarian insufficiency (POI), the potential mechanisms and the methods by which antioxidants can improve POI through controlling the level of OS. We found that OS can mediate changes in genetic materials, signal pathways, transcription factors and ovarian microenvironment, resulting in abnormal apoptosis of ovarian granulosa cells (GCs) and abnormal meiosis as well as decreased mitochondrial Deoxyribonucleic Acid(mtDNA) and other changes, thus accelerating the process of ovarian aging. However, antioxidants, mesenchymal stem cells (MSCs), biological enzymes and other antioxidants can delay the disease process of POI by reducing the ROS level in vivo.

Numerical investigation of water inflow and seepage characteristics in a tunnel crossing two overlapped parallel faults.

Water inflow is one of the main geohazards that threaten the safety of tunnels and other underground engineering projects. Faulted zone is one of the important geological triggers for such events. Numerical investigations on the evolution of flow behavior in tunnels across fault zones are of significance to the predication and prevention of this type of geohazards. In this work, a numerical investigation model with two overlapped parallel faults is established at a steady stage according to the "Three Zones" fault structure theory. The rapid turbulent flow in the fault zone is simulated by using the improved Darcy-Brinkman seepage model, while the slow laminar flow in ordinary rock zone is described by Darcy equation. The effect of relative position and distance between the tunnel excavation face and overlapped parallel faults to the groundwater pore pressure and flow velocity is studied through several scenarios, and the water inflow rate into the tunnel is calculated. The numerical investigation results reveal that while the tunnel face is excavated into the fault center core, the fractured zone, the ordinary rock zone, and the center of the overlapped faults, the pore pressure value ahead of the excavation face increases while the flow velocity decreases sequentially. The inflow rate is the largest while the tunnel face is excavated to center of the fault center core, which is closely related to the range of the overlapped area. The investigation results offer a practical reference for predicting early warning of water inflow geohazard when a tunnel cross two overlapped parallel faults.

Innovative Strategies for Hair Regrowth and Skin Visualization.

Today, about 50% of men and 15-30% of women are estimated to face hair-related problems, which create a significant psychological burden. Conventional treatments, including drug therapy and transplantation, remain the main strategies for the clinical management of these problems. However, these treatments are hindered by challenges such as drug-induced adverse effects and poor drug penetration due to the skin's barrier. Therefore, various efforts have been undertaken to enhance drug permeation based on the mechanisms of hair regrowth. Notably, understanding the delivery and diffusion of topically administered drugs is essential in hair loss research. This review focuses on the advancement of transdermal strategies for hair regrowth, particularly those involving external stimulation and regeneration (topical administration) as well as microneedles (transdermal delivery). Furthermore, it also describes the natural products that have become alternative agents to prevent hair loss. In addition, given that skin visualization is necessary for hair regrowth as it provides information on drug localization within the skin's structure, this review also discusses skin visualization strategies. Finally, it details the relevant patents and clinical trials in these areas. Together, this review highlights the innovative strategies for skin visualization and hair regrowth, aiming to provide novel ideas to researchers studying hair regrowth in the future.

Advanced materials and technologies for oral diseases.

Oral disease, as a class of diseases with very high morbidity, brings great physical and mental damage to people worldwide. The increasing burden and strain on individuals and society make oral diseases an urgent global health problem. Since the treatment of almost all oral diseases relies on materials, the rapid development of advanced materials and technologies has also promoted innovations in the treatment methods and strategies of oral diseases. In this review, we systematically summarized the application strategies in advanced materials and technologies for oral diseases according to the etiology of the diseases and the comparison of new and old materials. Finally, the challenges and directions of future development for advanced materials and technologies in the treatment of oral diseases were refined. This review will guide the fundamental research and clinical translation of oral diseases for practitioners of oral medicine.

Therapeutic effect and safety of curcumin in women with PCOS: A systematic review and meta-analysis.

Background: Polycystic ovary syndrome (PCOS) is a multi-factorial heterogeneous syndrome that has both adverse reproductive and metabolic implications for affected women and its management is a challenging clinical problem. Curcumin, as a phenolic compound with potent anti-inflammatory and antioxidant properties exerting positive effects on the lipid profile and insulin resistance, appears to be a valuable treatment regimen for patients with PCOS. Objective: This study aimed to evaluate the efficacy and safety of curcumin in the treatment of PCOS. Methods: Chinese databases (Chinese National Knowledge Infrastructure, China Biology Medicine Databases, VIP database, Wanfang Database, and Chinese Clinical Trial Registry) and English databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus and Clinical trials) were thoroughly investigated through screening randomized controlled trials on curcumin in PCOS published from the date of inception to May 2022. Standardized data search and abstraction were conducted following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Quantitative and qualitative analyses were performed. Heterogeneity was assessed using I2 statistics. Results: A total of 447 patients from seven randomized controlled trials were included in the meta-analysis. Results showed that the ingestion of curcumin decreased body mass index (WMD -0.267, 95% CI -0.450 to -0.084, P = 0.004, I2 = 0.0%), fasting plasma glucose (WMD -3.618, 95% CI -5.165 to -2.071, P < 0.001, I2 = 20.4%), insulin (WMD -1.834, 95% CI -2.701 to -0.968, P < 0.001, I2 = 8.4%), homeostatic model assessment for insulin resistance (WMD -0.565, 95% CI -0.779 to -0.351, P < 0.001, I2 = 0.0%), total cholesterol (WMD -15.591, 95% CI -27.908 to -3.273, P = 0.013, I2 = 68.9%), C-reactive protein (WMD -0.785, 95% CI -1.553 to -0.017, P = 0.045, I2 = 23.9%), and increased the quantitative insulin sensitivity check index (WMD 0.011, 95% CI 0.005 to 0.017, P = 0.001, I2 = 39.6%). As for safety, the treatment group did not cause significant adverse reactions than that in the control group. Conclusion: In light of presented findings, curcumin has beneficial effects on serum markers of inflammation, weight loss and glucose and lipid metabolism in patients with PCOS. The incidence of adverse reactions does not increase with the application of curcumin. However, a larger, more definitive study is needed to further investigate these results. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022332394.

The Application of Complementary and Alternative Medicine in Polycystic Ovary Syndrome Infertility.

Polycystic ovary syndrome (PCOS) is a lifelong reproductive endocrine disease, which is the most common cause of anovular infertility. Modern medicine mainly treats infertile patients with PCOS by improving living habits, ovulation induction therapy, and assisted reproductive technology (ART), but the effect is not satisfied. Complementary alternative medicine (CAM) has conspicuous advantages in the treatment of PCOS infertility due to its good clinical efficacy, wide mechanism of action, and no obvious adverse reactions, but its safety and effectiveness in the treatment of PCOS infertility have not been proved. Based on the existing clinical and experimental studies, this paper looks for the therapeutic effect and the mechanism behind it, and explores the safety and effectiveness of its treatment in PCOS infertility, in order to provide reference for future clinical treatment and experimental research.

Spontaneous rupture of the uterus in the third trimester after high-intensity ultrasound ablation in adenomyosis: A case report.

Adenomyosis is a benign uterine disease. Due to the higher incidence of adenomyosis and patients' demands for fertility, high-intensity ultrasound ablation has been widely used in gynecological patients with uterine fibroids and adenomyosis. Ultrasound ablation of lesions can help alleviate symptoms in patients without increasing the incidence of obstetric complications in subsequent pregnancies. High-intensity ultrasound ablation is not considered a risk factor for uterine rupture. However, we describe a case of adenomyosis treated with high-intensity ultrasound ablation presenting with uterine rupture in the third trimester. The patient underwent an emergency cesarean section to deliver the baby successfully and underwent uterine repair surgery. When treating patients with adenomyosis, care should be taken to protect the myometrium, endometrium, and serous layer to reduce the risk of uterine rupture.

The Effect of Age on IVF-ET Outcome in Infertile Patients with PCOS Based on Tiangui Theory in Chinese Medicine.

Objective: Our aim was to investigate the effect of age on the outcome of IVF-ET and ICSI in infertile PCOS patients under the guidance of Tiangui theory in traditional Chinese medicine. Method: This was a retrospective analysis of 532 infertile women with PCOS and 1,392 women with infertility due to tubal factors as the controls. All of the participants were divided into different age groups-aged 20-28 years, 29-35 years, and ≥36 years-according to the stages of female reproductive development in Tiangui theory as described in the Canon of Internal Medicine-Treatise of Ancient Natural Truth. We explored the effect of age on controlled ovarian hyperstimulation (including the initial dosage and duration of Gn and the estradiol level on the day of human chorionic gonadotropin administration); the numbers of retrieved oocytes, 2PN zygotes, and embryos; and the rates of fertilization, clinical pregnancy, abortion, live birth, and OHSS incidence. Results: Compared to controls, the maximum follicular diameter and the numbers of follicles with d ≥ 20 mm, retrieved oocytes, and 2PN zygotes were greater in the PCOS group with age >28 years (p < 0.05). The abortion rate of PCOS patients with age ≤28 years was higher than that of the controls. All PCOS groups and the control group showed reduced numbers of retrieved oocytes and live births with age. The difference in age was not significant in the PCOS groups but was significant in the control group (p < 0.05), and the trend in the PCOS groups was more gradual. Conclusion: The fertility of all subjects decreased with age, but PCOS patients decreased more slowly than in controls at the same age, which verified the applicability of the guiding principles of Tiangui theory in the clinic.

Therapeutic Potential of Menstrual Blood-Derived Stem Cell Transplantation for Intrauterine Adhesions.

An increasing number of women experience intrauterine adhesion as a result of intrauterine operations, such as induced abortion, which can cause infertility, recurrent abortion and amenorrhea. Although some strategies have been applied clinically, such as hysteroscopy adhesiolysis of intrauterine adhesions, the results have not been promising. As regenerative medicine develops, research on menstrual blood-derived stem cell transplantation is increasing due to the properties of these cells, including self-renewal, differentiation, angiogenesis, anti-inflammation and immunomodulation. As a result, menstrual blood-derived stem cells may be an ideal cell source for the treatment of intrauterine adhesion. Excitingly, it has been reported that autologous menstrual blood stem cells could recovery injured endometrium and improve infertility in patients with refractory intrauterine adhesion. In this review, we discuss the possible potential of menstrual blood-derived stem cell transplantation for intrauterine adhesion, including the antifibrosis, angiogenesis, anti-inflammation and immunoregulation properties of the cells, which brings hopes for clinical therapy.