A negative feedback loop between TET2 and leptin in adipocyte regulates body weight.

Ten-eleven translocation (TET) 2 is an enzyme that catalyzes DNA demethylation to regulate gene expression by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine, functioning as an essential epigenetic regulator in various biological processes. However, the regulation and function of TET2 in adipocytes during obesity are poorly understood. In this study, we demonstrate that leptin, a key adipokine in mammalian energy homeostasis regulation, suppresses adipocyte TET2 levels via JAK2-STAT3 signaling. Adipocyte Tet2 deficiency protects against high-fat diet-induced weight gain by reducing leptin levels and further improving leptin sensitivity in obese male mice. By interacting with C/EBPα, adipocyte TET2 increases the hydroxymethylcytosine levels of the leptin gene promoter, thereby promoting leptin gene expression. A decrease in adipose TET2 is associated with obesity-related hyperleptinemia in humans. Inhibition of TET2 suppresses the production of leptin in mature human adipocytes. Our findings support the existence of a negative feedback loop between TET2 and leptin in adipocytes and reveal a compensatory mechanism for the body to counteract the metabolic dysfunction caused by obesity.

Oral bacteriome and mycobiome of patients with idiopathic membranous nephropathy with different tongue coatings treated with a Chinese herbal formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. AIM OF THE STUDY: In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. MATERIALS AND METHODS: We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. RESULTS: The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. CONCLUSION: The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

Advancements in Photothermal Therapy Using Near-Infrared Light for Bone Tumors.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

Mendelian randomization and transcriptome analysis identified immune-related biomarkers for osteoarthritis.

Background: The immune microenvironment assumes a significant role in the pathogenesis of osteoarthritis (OA). However, the current biomarkers for the diagnosis and treatment of OA are not satisfactory. Our study aims to identify new OA immune-related biomarkers to direct the prevention and treatment of OA using multi-omics data. Methods: The discovery dataset integrated the GSE89408 and GSE143514 datasets to identify biomarkers that were significantly associated with the OA immune microenvironment through multiple machine learning methods and weighted gene co-expression network analysis (WGCNA). The identified signature genes were confirmed using two independent validation datasets. We also performed a two-sample mendelian randomization (MR) study to generate causal relationships between biomarkers and OA using OA genome-wide association study (GWAS) summary data (cases n = 24,955, controls n = 378,169). Inverse-variance weighting (IVW) method was used as the main method of causal estimates. Sensitivity analyses were performed to assess the robustness and reliability of the IVW results. Results: Three signature genes (FCER1G, HLA-DMB, and HHLA-DPA1) associated with the OA immune microenvironment were identified as having good diagnostic performances, which can be used as biomarkers. MR results showed increased levels of FCER1G (OR = 1.118, 95% CI 1.031-1.212, P = 0.041), HLA-DMB (OR = 1.057, 95% CI 1.045 -1.069, P = 1.11E-21) and HLA-DPA1 (OR = 1.030, 95% CI 1.005-1.056, P = 0.017) were causally and positively associated with the risk of developing OA. Conclusion: The present study identified the 3 potential immune-related biomarkers for OA, providing new perspectives for the prevention and treatment of OA. The MR study provides genetic support for the causal effects of the 3 biomarkers with OA and may provide new insights into the molecular mechanisms leading to the development of OA.

Electrospun polylactic acid nanofibers membrane with copper ion-loaded clay nanotubes for fresh-keeping packaging.

The plastics derived from fossil fuels for food packaging results in serious environmental problems. Developing environment-friendly materials for food packaging is urgent and essential. In this study, polylactic acid (PLA) composite nanofibers membranes were prepared with good biocompatibility and antibacterial property. Cu2+ loaded in the natural halloysite nanotubes (HNTs) was used for the antibacterial agent. Cu2+ was loaded in the HNTs and was confirmed by the X-ray photoelectron spectroscopy (XPS). PLA nanofibers with different HNTs-Cu content were continuous nanofibers with the nanoscale range. HNTs-Cu entered into the nanofiber successfully. Thermal analysis results showed composite nanofibers had good thermal stability. Composite nanofiber membranes had the good hydrophobic property. HNTs-Cu improved the mechanical property of composite nanofibers than pure PLA nanofibers. Tensile strength and elasticity modulus of composite nanofibers with 4 % HNTs-Cu content were the most outstanding. L929 cells were cultured on the nanofiber membranes for biocompatibility evaluation. Cell viability of nanofiber membranes was above the 90 %. Cell live/dead staining results showed L929 cells was seldom dead on the nanofiber membranes. PLA/HNTs-Cu nanofiber membranes exhibited excellent antibacterial effects on S. aureus and E. coli. The inhibitory rates against S. aureus and E. coli were 98.31 % and 97.80 % respectively. The fresh-keeping effects of nanofiber membranes were evaluated by the strawberry preservation. Strawberries covered by nanofiber membranes exhibited better appearance, lower weight loss and higher firmness than control, PLA and PLA/HNTs groups. It promised that PLA/HNTs-Cu composite nanofiber membranes have the significant potential application for active food packaging.

Exploration of the molecular biological mechanisms and review of postoperative radiotherapy cases in tenosynovial giant cell tumors.

Tendon Sheath Giant Cell Tumor (TGCT) is a benign tumor that primarily grows within joints and bursae. However, it has a high postoperative recurrence rate, ranging from 15% to 45%. Although radiotherapy may reduce this recurrence rate, its applicability as a standard treatment is still controversial. Furthermore, the pathogenic mechanisms of TGCT are not clear, which limits the development of effective treatment methods. The unpredictable growth and high recurrence rate of TGCT adds to the challenges of disease management. Currently, our understanding of TGCT mainly depends on pathological slice analysis due to a lack of stable cell models. In this study, we first reviewed the medical records of two female TGCT patients who had undergone radiotherapy. Then, by combining bioinformatics and machine learning, we interpreted the pathogenesis of TGCT and its associations with other diseases from multiple perspectives. Based on a deep analysis of the case data, we provided empirical support for postoperative radiotherapy in TGCT patients. Additionally, our further analysis revealed the signaling pathways of differentially expressed genes in TGCT, as well as its potential associations with osteoarthritis and synovial sarcomas.

Adipose stem cells control obesity-induced T cell infiltration into adipose tissue.

T cell infiltration into white adipose tissue (WAT) drives obesity-induced adipose inflammation, but the mechanisms of obesity-induced T cell infiltration into WAT remain unclear. Our single-cell RNA sequencing reveals a significant impact of adipose stem cells (ASCs) on T cells. Transplanting ASCs from obese mice into WAT enhances T cell accumulation. C-C motif chemokine ligand 5 (CCL5) is upregulated in ASCs as early as 4 weeks of high-fat diet feeding, coinciding with the onset of T cell infiltration into WAT during obesity. ASCs and bone marrow transplantation experiments demonstrate that CCL5 from ASCs plays a crucial role in T cell accumulation during obesity. The production of CCL5 in ASCs is induced by tumor necrosis factor alpha via the nuclear factor κB pathway. Overall, our findings underscore the pivotal role of ASCs in regulating T cell accumulation in WAT during the early phases of obesity, emphasizing their importance in modulating adaptive immunity in obesity-induced adipose inflammation.

[In vitro expression and functional analyses of the mutants p.R243Q, p.R241C and p.Y356X of the human phenylalanine hydroxylase]. / äººè‹¯ä¸™æ°¨é ¸ç¾ŸåŒ–é ¶çªå˜ä½“p.R243Q、p.R241C和p.Y356Xçš„ä½“å¤–è¡¨è¾¾åŠåŠŸèƒ½ç ”ç©¶.

OBJECTIVES: To study the in vitro expression of three phenylalanine hydroxylase (PAH) mutants (p.R243Q, p.R241C, and p.Y356X) and determine their pathogenicity. METHODS: Bioinformatics techniques were used to predict the impact of PAH mutants on the structure and function of PAH protein. Corresponding mutant plasmids of PAH were constructed and expressed in HEK293T cells. Quantitative reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the three PAH mutants, and their protein levels were assessed using Western blot and enzyme-linked immunosorbent assay. RESULTS: Bioinformatics analysis predicted that all three mutants were pathogenic. The mRNA expression levels of the p.R243Q and p.R241C mutants in HEK293T cells were similar to the mRNA expression level of the wild-type control (P>0.05), while the mRNA expression level of the p.Y356X mutant significantly decreased (P<0.05). The PAH protein expression levels of all three mutants were significantly reduced compared to the wild-type control (P<0.05). The extracellular concentration of PAH protein was reduced in the p.R241C and p.Y356X mutants compared to the wild-type control (P<0.05), while there was no significant difference between the p.R243Q mutant and the wild type control (P>0.05). CONCLUSIONS: p.R243Q, p.R241C and p.Y356X mutants lead to reduced expression levels of PAH protein in eukaryotic cells, with p.R241C and p.Y356X mutants also affecting the function of PAH protein. These three PAH mutants are to be pathogenic.

Regular use of aspirin and statins reduces the risk of cancer in individuals with systemic inflammatory diseases.

Aspirin has shown potential for cancer prevention, but a recent large randomized controlled trial found no evidence for a reduction in cancer risk. Given the anti-inflammatory effects of aspirin, systemic inflammatory diseases (SIDs), such as osteoporosis, cardiovascular diseases, and metabolic diseases, could potentially modify the aspirin-cancer link. To investigate the impact of aspirin in people with SIDs, we conducted an observational study on a prospective cohort of 478,615 UK Biobank participants. Individuals with at least one of the 41 SIDs displayed a higher cancer risk than those without SIDs. Regular aspirin use showed protective effects exclusively in patients with SID, contrasting an elevated risk among their non-SID counterparts. Nonetheless, aspirin use demonstrated preventative potential only for 9 of 21 SID-associated cancer subtypes. Cholesterol emerged as another key mediator linking SIDs to cancer risk. Notably, regular statin use displayed protective properties in patients with SID but not in their non-SID counterparts. Concurrent use of aspirin and statins exhibited a stronger protective association in patients with SID, covering 14 common cancer subtypes. In summary, patients with SIDs may represent a population particularly responsive to regular aspirin and statin use. Promoting either combined or individual use of these medications within the context of SIDs could offer a promising chemoprevention strategy.

Identification of abdominal aortic aneurysm subtypes based on mechanosensitive genes.

BACKGROUND: Rupture of abdominal aortic aneurysm (rAAA) is a fatal event in the elderly. Elevated blood pressure and weakening of vessel wall strength are major risk factors for this devastating event. This present study examined whether the expression profile of mechanosensitive genes correlates with the phenotype and outcome, thus, serving as a biomarker for AAA development. METHODS: In this study, we identified mechanosensitive genes involved in AAA development using general bioinformatics methods and machine learning with six human datasets publicly available from the GEO database. Differentially expressed mechanosensitive genes (DEMGs) in AAAs were identified by differential expression analysis. Molecular biological functions of genes were explored using functional clustering, Protein-protein interaction (PPI), and weighted gene co-expression network analysis (WGCNA). According to the datasets (GSE98278, GSE205071 and GSE165470), the changes of diameter and aortic wall strength of AAA induced by DEMGs were verified by consensus clustering analysis, machine learning models, and statistical analysis. In addition, a model for identifying AAA subtypes was built using machine learning methods. RESULTS: 38 DEMGs clustered in pathways regulating 'Smooth muscle cell biology' and 'Cell or Tissue connectivity'. By analyzing the GSE205071 and GSE165470 datasets, DEMGs were found to respond to differences in aneurysm diameter and vessel wall strength. Thus, in the merged datasets, we formally created subgroups of AAAs and found differences in immune characteristics between the subgroups. Finally, a model that accurately predicts the AAA subtype that is more likely to rupture was successfully developed. CONCLUSION: We identified 38 DEMGs that may be involved in AAA. This gene cluster is involved in regulating the maximum vessel diameter, degree of immunoinflammatory infiltration, and strength of the local vessel wall in AAA. The prognostic model we developed can accurately identify the AAA subtypes that tend to rupture.

Mosaic GJB2 mutations in widespread porokeratotic adnexal ostial nevus: Report of two patients.

Porokeratotic adnexal ostial nevus (PAON) is a rare adnexal hamartoma characterized by keratotic papules following Blaschko's lines, typically located on the unilateral distal extremities. Cutaneous somatic GJB2 mutations have been linked to the pathogenesis of PAON. However, the genetic mechanism underlying bilateral or extended forms, which are less documented, remains unknown. In this study, we presented two cases of PAON with widespread cutaneous lesions and scalp involvement, and demonstrated the presence of GJB2 mosaic mutations in both patients. We further investigated the mosaic frequency in different tissues to gain insights into the mutation events contributing to the phenotype of widespread PAON. Our findings suggest that early postzygotic mutation causing mosaic GJB2 mutations may contribute to the widespread phenotype of PAON, thereby enriching the disease spectrum and mutation profile of PAON.

Application research of novel peptide mitochondrial-targeted antioxidant SS-31 in mitigating mitochondrial dysfunction.

Due to the pivotal role of mitochondria in the generation of adenosine triphosphate (ATP) and the regulation of cellular homeostasis, mitochondrial dysfunction may exert a profound impact on various physiological systems, potentially precipitating a spectrum of distinct diseases. Consequently, research pertaining to mitochondrial therapeutics has assumed increasing significance, warranting heightened scrutiny. In recent years, the field of mitochondrial therapy has witnessed noteworthy advancements, with active exploration into diverse pharmacological agents aimed at ameliorating mitochondrial function. Elamipretide (SS-31), a novel synthetic mitochondrial-targeted antioxidant, has emerged as a promising candidate with extensive therapeutic potential. Its notable attributes encompass the mitigation of oxidative stress, the suppression of inflammatory processes, the maintenance of mitochondrial dynamics, and the prevention of cellular apoptosis. As such, SS-31 may emerge as a viable choice for the treatment of mitochondrial dysfunction-related ailments in the foreseeable future. This article extensively expounds upon the superiority of SS-31 over natural antioxidants and traditional mitochondrial-targeted antioxidants, delves into its mechanisms of modulating mitochondrial function, and comprehensively summarizes its applications in alleviating mitochondrial dysfunction-associated disorders. Furthermore, we offer a comprehensive outlook on the expansive prospects of SS-31's future development and application.

Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in initiating ART among HIV-Infected patients in China-risk factors and management.

BACKGROUND: China is a country burdened with a high incidence of both tuberculosis (TB) and HIV, Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an important early complication in TB and HIV co-infected patients, but data from China are limited. Additionally, as an integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) regimen becomes the first-line treatment, concerns have arisen regarding the potential increase in the incidence of paradoxical TB-IRIS. Nevertheless, the existing data are inconclusive and contradictory. METHODS: We conducted a retrospective study at Chongqing Public Health Clinical Center from January 2018 to December 2021. We collected demographic and clinical data of HIV/TB co-infected patients who initiated ART. We described the patient characteristics, identified predictors for TB-IRIS, and determined clinical outcomes. The Statistical Package for Social Science (SPSS 25) was used to analyse the data. Continuous variables were compared using Student's t-test or rank sum test. Counting data were compared using the chi-square test or Fisher's exact test. The variables with statistical significance in the univariate analysis were added to the binary logistic regression. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 384 patients co-infected with naive HIV and pulmonary TB (PTB) who were given ATT and ART combination were included. 72 patients (18.8%) developed paradoxical TB-IRIS with a median of 15 (12, 21) days after initiating ART. Baseline age ≤ 40years, CD4 + T-cell counts ≤ 50cells/µL, HIV viral load ≥ 500,000 copies/mL were found to be significantly associated with development of paradoxical TB-IRIS. Mortality rates were similar in the TB-IRIS (n = 5, 6.9%) group and non-TB-IRIS (n = 13, 4.2%) group. Interestingly, CD4+ T-cell counts recovery post-ART was significant higher in the TB-IRIS group when compared to the non-TB-IRIS group at the end of 24 weeks (P = 0.004), as well as at 48 weeks (P = 0.015). In addition, we consider that INSTI- based ART regimen do not increased the risk of Paradoxical TB-IRIS. CONCLUSION: Paradoxical TB-IRIS, while often leading to clinical deterioration and hospitalization, is generally manageable. It appears to have a positive impact on the recovery of CD4 + T-cell counts over time. Importantly, our data suggest that INSTI-based ART regimens do not elevate the risk of TB-IRIS. Thus, paradoxical TB-IRIS should not be considered an impediment to initiating ART in adults with advanced immunodeficiency, except in the case of tuberculous meningitis (TBM).

Dual chemodynamic/photothermal therapeutic nanoplatform based on DNA-functionalized prussian blue.

The combination of chemodynamic therapy and photothermal therapy has a promising application owing to its impressive anti-cancer effects. However, the degradability of the material and the lack of targeting severely limit its further clinical application. Herein, DNAs containing nucleolin aptamer (AS1411) and different bases sequences were used to functionalize PB NPs for the targeted treatment. Compared to prussian blue, DNA-functionalized prussian blue does not reduce the photothermal properties of prussian blue. Moreover, DNA confers DNA-functionalized prussian blue targeting and higher enzymatic activity, thereby achieving a more effective combination of chemodynamic and photothermal treatment. The therapeutic efficacy of this nanoplatform was evaluated in vivo and in vitro experiments, exhibiting that DNA-functionalized prussian blue nanozyme can maximize the precise control of the therapeutic effect, reduce the toxic and side effects caused by non-specific accumulation on other normal cells, and effectively achieve targeted killing of cancer cells. This work demonstrates that DNA-functionalized prussian blue can improve the efficiency of combined tumor treatment and enhance the application value of prussian blue in tumor treatment, which is expected to provide theoretical support for clinical application.

High-Contrast Photoacoustic Imaging of Localized Cysteine in Orthotopic Breast Cancer Enabled by A Totally-Caged Methylene Blue Probe.

High-contrast photoacoustic sensing imaging (PASI) was greatly determined by optical absorption changes of the absorbers usually enabled by activatable probes via controllably converting the absorbed electromagnetic energy to ultrasound waves. However, most of current photoacoustic probes still suffer from limited imaging contrast towards specific species because of their small absorption spectral changes in the near infrared (NIR) region. Herein, we developed a methylene blue-based photoacoustic probe with its NIR optical absorption totally caged, which could afford dramatical "OFF-to-ON" absorption transition for high-contrast photoacoustic imaging towards the localized cysteine. The rationally designed methylene blue-based probe for cysteine (MB-Cys) would keep in off state with almost no absorption in NIR region, while upon activated by cysteine through cyclization reaction with acrylates, it would reconstruct the π-conjugation system to release the free methylene blue with strong absorption centered at 665 nm (>130-fold enhancement). The unique responsive behavior could enable the PASI for photoacoustic mapping the cysteine in orthotopic breast cancer in a high-contrast manner. Therefore, this work established an up-to-date strategy to originally eliminate the background photoacoustic signal for PASI to accurately monitor cysteine in vivo.

Comparison of the efficacy of different frequency electroacupuncture in the treatment of polycystic ovary syndrome patients with abdominal obesity. / ä¸åŒé¢‘çŽ‡ç”µé’ˆæ²»ç–—è ¹éƒ¨è‚¥èƒ–åž‹å¤šå›Šåµå·¢ç»¼åˆå¾çš„ç–—æ•ˆæ¯”è¾ƒ.

OBJECTIVES: To compare the effects of 2 Hz continuous wave and 2 Hz/100 Hz dilatational wave setting in electroacupuncture(EA) on ovulation frequency, hormone levels, body fat parameters, quality of life and depression-anxiety level in polycystic ovary syndrome (PCOS) patients with abdominal obesity. METHODS: PCOS patients with abdominal obesity were randomly divided into low-frequency group (n=29) and dilatational wave group (n=29). Patients in both groups were treated with "Tongtiaodaimai" (regulating Dai Meridian) acupuncture therapy, and EA was applied to bilateral Daimai (GB26), Tianshu (ST25), Shenshu (BL23) and Ciliao (BL32). The low-frequency group received EA using a continuous wave at a frequency of 2 Hz, while the dilatational wave group received dilatational wave at a frequency of 2 Hz/100 Hz. Both groups received treatment for 30 min each time, 3 times per week for 12 consecutive weeks. Ovulation frequency was calculated according to the ovulation cycle. The contents of serum anti-Mullerian hormone (AMH) and sex hormone binding globulin (SHBG) were detected with electrochemiluminescence method. Body weight (BW) and waist circumference (WC) were measured, and body mass index (BMI) and waist-height ratio (WHtR) were calculated. PCOS questionnaire (Chi-PCOSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were evaluated. RESULTS: Compared with before treatment, both the low-frequency group and the dilatational wave group showed an increase in ovulation frequency (P<0.01, P<0.05), and a decrease in BW, BMI, WC, WHtR, and SDS score (P<0.01, P<0.05)；the dilatational wave group showed decreased serum AMH contents (P<0.05) and increased serum SHBG contents (P<0.05), the scores related to acne, fatigue, and dysmenorrhea in the Chi-PCOSQ increased (P<0.01, P<0.05). Compared with the low-frequency group, the dilatational wave group showed a reduction (P<0.05) in WC after treatment. CONCLUSIONS: 2 Hz/100 Hz dilatational wave EA is equally effective as 2 Hz low-frequency EA in improving ovulation frequency. In terms of reducing WC in abdominal obesity type PCOS patients, 2 Hz/100 Hz dilatational wave EA is superior to 2 Hz low-frequency EA. 2 Hz/100 Hz dilatational wave EA can decrease serum AMH, increase serum SHBG, and improve symptoms of acne, fatigue, and dysmenorrhea.

The role of toll-like receptors in orchestrating osteogenic differentiation of mesenchymal stromal cells and osteoimmunology.

Osteoimmunology is a concept involving molecular and cellular crosstalk between the skeletal and immune systems. Toll-like receptors (TLRs) are widely expressed both on mesenchymal stromal cells (MSCs), the hematopoietic cells, and immune cells in the osteogenic microenvironment for bone development or repair. TLRs can sense both exogenous pathogen-associated molecular patterns (PAMPs) derived from microorganisms, and damage-associated molecular patterns (DAMPs) derived from normal cells subjected to injury, inflammation, or cell apoptosis under physiological or pathological conditions. Emerging studies reported that TLR signaling plays an important role in bone remodeling by directly impacting MSC osteogenic differentiation or osteoimmunology. However, how to regulate TLR signaling is critical and remains to be elucidated to promote the osteogenic differentiation of MSCs and new bone formation for bone tissue repair. This review outlines distinct TLR variants on MSCs from various tissues, detailing the impact of TLR pathway activation or inhibition on MSC osteogenic differentiation. It also elucidates TLR pathways' interplay with osteoclasts, immune cells, and extracellular vesicles (EVs) derived from MSCs. Furthermore, we explore biomaterial-based activation to guide MSCs' osteogenic differentiation. Therefore, understanding TLRs' role in this context has significant implications for advancing bone regeneration and repair strategies.

A dye-quenched/sensitized switching upconversion nanoprobe for high-contrast mapping of the pH-related tumor microenvironment.

Nanoprobes based on lanthanide-doped upconversion nanoparticles (UCNPs) exhibit promising potential in bioimaging and biosensing due to their unique optical properties. However, conventional UCNP nanoprobes based on the dye quenching effect are still limited in biosensing due to their low upconversion efficiency. The advent of dye-sensitized upconversion has resulted in nanoprobes with significantly enhanced efficiency; however, these still suffer from a high initial emissive background. In view of this, herein, we have constructed a dye-quenched/sensitized switching upconversion nanoprobe for high-contrast imaging of the pH-related tumor microenvironment. Under normal conditions, the luminescence of the nanoprobe at 540 nm (UCL540) was significantly quenched by the employed dye. Upon being triggered by an acid, the dye would switch to its fluorescent form to sensitize the luminescence of UCNPs, affording a significant enhancement of UCL540. The switching from dye-quenched UCL to dye-sensitized UCL jointly enables the detection of a high signal-to-background ratio (high up to 50), allowing for high-contrast mapping of the tumor specific acidic microenvironment in vivo. We believe that this nanoplatform holds considerable promise for acid-related sensing.

Advances in the mechanisms related to follicle loss after frozen-thawed ovarian tissue transplantation.

Ovaries are important reproductive and endocrine organs in women. Ovarian tissue cryopreservation and transplantation technology can not only solve the fertility problems of patients, but also may improve female endocrine problems. This is particularly important for patients in urgent need of radiotherapy and chemotherapy, and for women with prepubertal malignant tumors. However, follicle loss after freeze-thawing is a key challenge for effective ovarian tissue transplantation and leads to poor transplant outcomes. Therefore, it is crucial to elucidate the mechanisms underlying follicle loss after transplantation. This paper reviews current research on the mechanisms of follicle loss after frozen-thawed ovarian tissue transplantation, including the activation, apoptosis, and pyroptosis mechanisms of primordialfollicles. Further, it highlights the requirement of more experimental studies for improving ovarian tissue transplantation methods.