Investigating the Genetic Association of 40 Biochemical Indicators with Parkinson's Disease.

The mechanisms of Parkinson's disease (PD) are not fully understood, which hinders the development of effective therapies. Research indicates that lower levels of biochemical indicators like bilirubin, vitamin D, and cholesterol may elevate the risk of PD. However, clinical studies on abnormal levels of biochemical indicators in PD patients' circulation are inconsistent, leading to ongoing debate about their association with PD. Here, we investigate the genetic correlation between 40 biochemical indicators and PD using a bidirectional two-sample Mendelian randomization (MR) approach to uncover potential causal relationships. Data from genome-wide association studies (GWAS) were utilized, with genetic variations from specific lineages serving as instrumental variables (IVs). The methodology followed the STROBE-MR checklist and adhered to the three principal assumptions of MR. Statistical analyses employed methods including inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode. Biochemical indicators including albumin, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) showed significant associations with PD risk. Elevated levels of albumin (OR = 1.246, 95% CI 1.006-1.542, P = 0.043) and SHBG (OR = 1.239, 95% CI 1.065-1.439, P = 0.005) were linked to higher PD risk. Conversely, increased CRP levels (OR = 0.663, 95% CI 0.517-0.851; P = 0.001) could potentially lower PD risk. The robustness of the results was confirmed through various MR analysis techniques, including assessments of directional pleiotropy and heterogeneity using MR-Egger intercept and MR-PRESSO methods. This study systematically reveals, for the first time at the genetic level, the relationship between 40 biochemical indicators and PD risk. Our research verifies the role of inflammation in PD and provides new genetic evidence, further advancing the understanding of PD pathogenesis. The study shows a positive correlation between albumin and SHBG with PD risk and a negative correlation between CRP and PD risk. This study identifies for the first time that SHBG may be involved in the onset of PD and potentially worsen disease progression.

Pushing Theoretical Potassium Storage Limits of MXenes through Introducing New Carbon Active Sites.

Surface-driven capacitive storage enhances rate performance and cyclability, thereby improving the efficacy of high-power electrode materials and fast-charging batteries. Conventional defect engineering, widely-employed capacitive storage optimization strategy, primarily focuses on the influence of defects themselves on capacitive behaviors. However, the role of local environment surrounding defects, which significantly affects surface properties, remains largely unexplored for lack of suitable material platform and has long been neglected. As proof-of-concept, typical Ti3C2Tx MXenes are chosen as model materials owing to metallic conductivity and tunable surface properties, satisfying the requirements for capacitive-type electrodes. Using density functional theory (DFT) calculations, the potential of MXenes with modulated local atomic environment is anticipated and introducing new carbon sites found near pores can activate electrochemically inert surface, attaining record theoretical potassium storage capacities of MXenes (291 mAh g-1). This supposition is realized through atomic tailoring via chemical scissor within sublayers, exposing new sp3-hybridized carbon active sites. The resulting MXenes demonstrate unprecedented rate performance and cycling stability. Notably, MXenes with higher carbon exposure exhibit a record-breaking capacity over 200 mAh g-1 and sustain a capacity retention higher than 80% after 20 months. These findings underscore the effectiveness of regulating defects' neighboring environment and illuminate future high-performance electrode design.

Recombinant filaggrin-2 improves skin barrier function and attenuates ultraviolet B (UVB) irradiation-induced epidermal barrier disruption.

The integrity of the skin barrier is essential for maintaining skin health, with the stratum corneum and filaggrin 2 (FLG-2) playing a key role. FLG-2 deficiency or mutation has been linked to diseases such as atopic dermatitis, while external stressors such as ultraviolet B (UVB) radiation further damage the epidermal barrier. This study investigated the effects of recombinant filaggrin (rFLG) on skin barrier function and UVB induced epidermal destruction. Cell experiments showed that 10 µg/mL of rFLG could increase the mobility of HaCaT cells from 20 % to 42 %, increase the epithelial resistance (TEER) value by about 2 times, and up-regulate the tight junction associated protein by about 2 times. In mouse models of UVB-induced epidermal barrier destruction, rFLG at concentrations of 0.5, 1, and 2 mg/mL showed effective cell uptake and skin penetration, alleviating erythema, and reducing skin thickness in mice by 1.5-3 times. Among them, 2 mg/mL of rFLG treatment restored the expression of tight junction proteins (LOR, ZO-1, and caspase-14), reduced collagen degradation, and reduced oxidative stress by normalizing serum hydroxyproline and superoxide dismutase levels. In addition, 2 mg/mL of rFLG inhibited UVB-induced upregulation of matrix metalloproteinases (MMP-3 and MMP-9) and reduced pro-inflammatory factors (IL-10, IL-1α, IL-6, and TNF-α) and apoptotic markers (P38, Bax, and Bcl-2) to normal levels. These findings suggested that rFLG effectively enhanced skin barrier integrity and mitigated UVB-induced epidermal barrier destruction, highlighting its potential as a therapeutic agent for diseases associated with skin barrier dysfunction.

Ultra-Photostable Bacterial-Seeking Near-Infrared CPDs for Simultaneous NIR-II Bioimaging and Antibacterial Therapy.

Bacterial infections can pose significant health risks as they have the potential to cause a range of illnesses. These infections can spread rapidly and lead to complications if not promptly diagnosed and treated. Therefore, it is of great significance to develop a probe to selectively target and image pathogenic bacteria while simultaneously killing them, as there are currently no effective clinical solutions available. This study presents a novel approach using near-infrared carbonized polymer dots (NIR-CPDs) for simultaneous in vivo imaging and treatment of bacterial infections. The core-shell structure of the NIR-CPDs facilitates their incorporation into bacterial cell membranes, leading to an increase in fluorescence brightness and photostability. Significantly, the NIR-CPDs exhibit selective bacterial-targeting properties, specifically identifying Staphylococcus aureus (S. aureus) while sparing Escherichia coli (E. coli). Moreover, under 808 nm laser irradiation, the NIR-CPDs exhibit potent photodynamic effects by generating reactive oxygen species that target and damage bacterial membranes. In vivo experiments on infected mouse models demonstrate not only precise imaging capabilities but also significant therapeutic efficacy, with marked improvements in wound healing. The study provides the dual-functional potential of NIR-CPDs as a highly effective tool for the advancement of medical diagnostics and therapeutics in the fight against bacterial infections.

Periodic Flows in Microfluidics.

Microfluidics, the science and technology of manipulating fluids in microscale channels, offers numerous advantages, such as low energy consumption, compact device size, precise control, fast reaction, and enhanced portability. These benefits have led to applications in biomedical assays, disease diagnostics, drug discovery, neuroscience, and so on. Fluid flow within microfluidic channels is typically in the laminar flow region, which is characterized by low Reynolds numbers but brings the challenge of efficient mixing of fluids. Periodic flows are time-dependent fluid flows, featuring repetitive patterns that can significantly improve fluid mixing and extend the effective length of microchannels for submicron and nanoparticle manipulation. Besides, periodic flow is crucial in organ-on-a-chip (OoC) for accurately modeling physiological processes, advancing disease understanding, drug development, and personalized medicine. Various techniques for generating periodic flows have been reported, including syringe pumps, peristalsis, and actuation based on electric, magnetic, acoustic, mechanical, pneumatic, and fluidic forces, yet comprehensive reviews on this topic remain limited. This paper aims to provide a comprehensive review of periodic flows in microfluidics, from fundamental mechanisms to generation techniques and applications. The challenges and future perspectives are also discussed to exploit the potential of periodic flows in microfluidics.

Prognostic value of serum total IgE and FeNO levels in children with atopic constitution bronchiolitis.

Bronchiolitis is a significant factor contributing to bronchial asthma in infants and young children. After treatment, recurrent wheezing symptoms often occur, especially in children with atopic constitution, who tend to have more severe conditions and poorer prognosis. Therefore, exploring the prognostic value of total serum immunoglobulin E (tIgE) and fractional exhaled nitric oxide (FeNO) levels in children with atopic constitution who suffer from bronchiolitis is of great significance. A total of 260 children with bronchiolitis admitted to our hospital from October 2020 to June 2022 were regarded as the research subjects with prospective study, according to whether the children had atopic constitution, they were grouped into non atopic constitution group (n = 156) and atopic constitution group (n = 104); after 6 months of treatment, children with atopic constitution were grouped into a good prognosis group (n = 58) and a poor prognosis group (n = 46) based on their prognosis; in addition, 260 healthy children who underwent physical examination and had clinical data consistent with those of children with bronchiolitis were regarded as the reference group. The serum tIgE and FeNO levels of each group were compared; multivariate Logistic regression was applied to analyze the prognostic factors of children with atopic constitution bronchiolitis; ROC curve was applied to analyze the predictive value of tIgE and FeNO levels after treatment for the prognosis of children with atopic constitution bronchiolitis. The tIgE levels in the control group, non-atopic group, and atopic group [(123.54 ± 29.62) IU/mL, (245.71 ± 30.59) IU/mL, (316.46 ± 31.78) IU/mL, respectively] increased sequentially, with statistically significant differences (F = 1766.954, P = 0.000). The FeNO levels in the control group, non-atopic group, and atopic group [(8.36 ± 3.57) ppb, (15.28 ± 3.69) ppb, (19.84 ± 3.58) ppb, respectively] also increased sequentially, with statistically significant differences (F = 765.622, P = 0.000). The tIgE, FeNO, proportion of patients with asthma family history, and proportion of patients with allergic family history in the poor prognosis group were obviously higher than those in the good prognosis group (P < 0.05). Multivariate Logistic regression analysis showed that family history of asthma, family history of allergies, tIgE, and FeNO were influencing factors for the prognosis of children with atopic bronchiolitis (P < 0.05). The AUC of the combination of tIgE and FeNO in predicting the prognosis of children with atopic constitutional bronchiolitis was 0.910, with a sensitivity of 78.26% and a specificity of 93.10%, which was superior to the independent prediction of tIgE and FeNO (Zcombined detection-tIgE = 2.442, Zcombined detection-FeNO = 3.080, P = 0.015, 0.002). The levels of tIgE and FeNO in children with atopic constitution bronchiolitis are obviously increased, and the combination of the two has high predictive value for the prognosis of atopic constitution bronchiolitis.

Dermal Injection of Recombinant Filaggrin-2 Ameliorates UVB-Induced Epidermal Barrier Dysfunction and Photoaging.

The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the adverse effects of UV-induced barrier disruption and photoaging remains poorly understood. In this study, we revealed that UVB exposure resulted in a decreased expression of FLG2 in HaCaT keratinocytes, which correlated with a compromised barrier function. The administration of recombinant filaggrin-2 (rFLG2) enhanced keratinocyte differentiation, bolstered barrier integrity, and offered protection against apoptosis and oxidative stress induced by UVB irradiation. Furthermore, in a UV-induced photodamage murine model, the dermal injection of rFLG2 facilitated the enhanced restoration of the epidermal barrier, decreased oxidative stress and inflammation, and mitigated the collagen degradation that is typical of photoaging. Collectively, our findings suggested that targeting FLG2 could be a strategic approach to prevent and treat skin barrier dysfunction and combat the aging effects associated with photoaging. rFLG2 emerges as a potentially viable therapy for maintaining skin health and preventing skin aging processes amplified by photodamage.

Disorder of neuroplasticity aggravates cognitive impairment via neuroinflammation associated with intestinal flora dysbiosis in chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) impairs cognitive function, yet its effects on brain structure and underlying mechanisms remain elusive. This study aims to explore the mechanisms behind cognitive impairment. METHODS: CHF models in rats were induced by ligation of the left anterior descending coronary artery. Cardiac function was analyzed by cardiac ultrasound and hemodynamics. ELISA, immunofluorescence, Western blot, Golgi staining and transmission electron microscopy were performed on hippocampal tissues. The alterations of intestinal flora under the morbid state were investigated via 16S rRNA sequencing. The connection between neuroinflammation and synapses is confirmed by a co-culture system of BV2 microglia and HT22 cells in vitro. Results: CHF rats exhibited deteriorated cognitive behaviors. CHF induced neuronal structural disruption, loss of Nissl bodies, and synaptic damage, exhibiting alterations in multiple parameters. CHF rats showed increased hippocampal levels of inflammatory cytokines and activated microglia and astrocytes. Furthermore, the study highlights dysregulated PDE4-dependent cAMP signaling and intestinal flora dysbiosis, closely associated with neuroinflammation, and altered synaptic proteins. In vitro, microglial neuroinflammation impaired synaptic plasticity via PDE4-dependent cAMP signaling. CONCLUSIONS: Neuroinflammation worsens CHF-related cognitive impairment through neuroplasticity disorder, tied to intestinal flora dysbiosis. PDE4 emerges as a potential therapeutic target. These findings provide insightful perspectives on the heart-gut-brain axis.

[Research progress on clinically effective single preparations of traditional Chinese medicine].

The traditional Chinese medicine(TCM) single preparation refers to the innovative TCM made from the whole or the effective part(including the effective ingredient) extract of a TCM single herb by modern technology. They have a long history of applications, definite effects and few side effects. It is an indispensable part of the research of innovative TCM. In recent years, with the optimization of national policies, the development of TCM single preparation shows a positive trend. However, because of the imbalance in the composition ratio, the need for expansion of indications, the need for further basic research, and the low conversion rate of existing patent achievements in universities and institutes, the TCM single preparation still has significant development space. In this review, we analyze and study the current situation, characteristics and difficulties of TCM single preparation, as well as relevant clinical application, basic research, industrialization and patent application information through statistical analysis of TCM single preparations in the Chinese Pharmacopoeia, which helps to provide direction for the development and research of single preparation of TCM.

Middle and Late Pleistocene Denisovan subsistence at Baishiya Karst Cave.

Genetic and fragmented palaeoanthropological data suggest that Denisovans were once widely distributed across eastern Eurasia1-3. Despite limited archaeological evidence, this indicates that Denisovans were capable of adapting to a highly diverse range of environments. Here we integrate zooarchaeological and proteomic analyses of the late Middle to Late Pleistocene faunal assemblage from Baishiya Karst Cave on the Tibetan Plateau, where a Denisovan mandible and Denisovan sedimentary mitochondrial DNA were found3,4. Using zooarchaeology by mass spectrometry, we identify a new hominin rib specimen that dates to approximately 48-32 thousand years ago (layer 3). Shotgun proteomic analysis taxonomically assigns this specimen to the Denisovan lineage, extending their presence at Baishiya Karst Cave well into the Late Pleistocene. Throughout the stratigraphic sequence, the faunal assemblage is dominated by Caprinae, together with megaherbivores, carnivores, small mammals and birds. The high proportion of anthropogenic modifications on the bone surfaces suggests that Denisovans were the primary agent of faunal accumulation. The chaîne opératoire of carcass processing indicates that animal taxa were exploited for their meat, marrow and hides, while bone was also used as raw material for the production of tools. Our results shed light on the behaviour of Denisovans and their adaptations to the diverse and fluctuating environments of the late Middle and Late Pleistocene of eastern Eurasia.

Prognosis and immunotherapy in melanoma based on selenoprotein k-related signature.

Selenium and selenoproteins are closely related to melanoma progression. However, it is unclear how SELENOK affects lipid metabolism, endoplasmic reticulum stress (ERS), immune cell infiltration, survival, and prognosis in melanoma patients. Transcriptome data from melanoma patients was used to investigate SELENOK levels and their effect on prognosis, followed by an investigation of SELENOK's effects on immune cell infiltration. Furthermore, a risk model based on ERS, lipid metabolism, and immune-related genes was constructed, and its utility in melanoma prognosis was evaluated. Finally, the drug sensitivity of the risk model was analyzed to provide a reference for melanoma therapy. The results showed that melanoma with a high SELENOK level had a greater degree of immune cell infiltration and a better prognosis. Additionally, SELENOK was found to regulate ERS, lipid metabolism, and immune cell infiltration in melanoma. The risk model based on SELENOK signature genes successfully predicted the prognosis of melanoma, and the low-risk group exhibited a favorable immunological microenvironment. Furthermore, high-risk patients with melanoma were candidates for chemotherapy with RAS pathway inhibitors, whereas low-risk patients were more susceptible to routinely used chemotherapy medicines. In summary, SELENOK was shown to regulate ERS, lipid metabolism, and immune cell infiltration in melanoma, and SELENOK was positively associated with the prognosis of melanoma. The risk model based on SELENOK signature genes was valuable for melanoma prognosis and therapy.

Hormone Regulation in Testicular Development and Function.

The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.

Shenqi Fuzheng injection facilitates skeletal muscle mitophagy mediated by the ubiquitination of HIF-1α to ameliorate cancer-associated fatigue.

Cancer-related fatigue (CRF) significantly impacts the quality of life of cancer patients. This study investigates the therapeutic potential of Shenqi Fuzheng injection (SFI) in managing CRF, focusing on its mechanistic action in skeletal muscle. We utilized a CRF mouse model to examine the effects of SFI on physical endurance, monitoring activity levels, swimming times and rest periods. Proteomic analysis of the gastrocnemius muscle was performed using isobaric tags and liquid chromatography-tandem mass spectrometry to map the muscle proteome changes post-SFI treatment. Mitochondrial function in skeletal muscle was assessed via ATP bioluminescence assay. Furthermore, the regulatory role of the hypoxia inducible factor 1 subunit alpha (HIF-1α) signalling pathway in mediating SFI's effects was explored through western blotting. In CRF-induced C2C12 myoblasts, we evaluated cell viability (CCK-8 assay), apoptosis (flow cytometry) and mitophagy (electron microscopy). The study also employed pulldown, luciferase and chromatin immunoprecipitation assays to elucidate the molecular mechanisms underlying SFI's action, particularly focusing on the transcriptional regulation of PINK1 through HIF-1α binding at the PINK1 promoter region. Our findings reveal that SFI enhances physical mobility, reduces fatigue symptoms and exerts protective effects on skeletal muscles by mitigating mitochondrial damage and augmenting antioxidative responses. SFI promotes cell viability and induces mitophagy while decreasing apoptosis, primarily through the modulation of HIF-1α, PINK1 and p62 proteins. These results underscore SFI's efficacy in enhancing mitochondrial autophagy, thereby offering a promising approach for ameliorating CRF. The study not only provides insight into SFI's potential therapeutic mechanisms but also establishes a foundation for further exploration of SFI interventions in CRF management.

Potential Gradient-Driven Dual-Functional Electrochromic and Electrochemical Device Based on a Shared Electrode Design.

The integration of electrochromic devices and energy storage systems in wearable electronics is highly desirable yet challenging, because self-powered electrochromic devices often require an open system design for continuous replenishment of the strong oxidants to enable the coloring/bleaching processes. A self-powered electrochromic device has been developed with a close configuration by integrating a Zn/MnO2 ionic battery into the Prussian blue (PB)-based electrochromic system. Zn and MnO2 electrodes, as dual shared electrodes, the former one can reduce the PB electrode to the Prussian white (PW) electrode and serves as the anode in the battery; the latter electrode can oxidize the PW electrode to its initial state and acts as the cathode in the battery. The bleaching/coloring processes are driven by the gradient potential between Zn/PB and PW/MnO2 electrodes. The as-prepared Zn||PB||MnO2 system demonstrates superior electrochromic performance, including excellent optical contrast (80.6%), fast self-bleaching/coloring speed (2.0/3.2 s for bleaching/coloring), and long-term self-powered electrochromic cycles. An air-working Zn||PB||MnO2 device is also developed with a 70.3% optical contrast, fast switching speed (2.2/4.8 s for bleaching/coloring), and over 80 self-bleaching/coloring cycles. Furthermore, the closed nature enables the fabrication of various flexible electrochromic devices, exhibiting great potentials for the next-generation wearable electrochromic devices.

Beetle-inspired AuNPs semi-embedded colloidal crystal chips for the highly sensitive and colored detection of chloramphenicol in foods.

Inspired by the desert beetle, a novel biomimetic chip was developed to detect chloramphenicol (CP). The chip was characterized by a periodic array in which hydrophobic Au nanoparticles (AuNPs) were semi-embedded on hydrophilic polymethyl methacrylate (PMMA) spheres. Among them, the AuNPs exhibited both a localized surface plasmon resonance effect to amplify the reflected signal and a synergistic effect with PMMA spheres to create a significant hydrophilic-hydrophobic interface, which facilitated the enrichment of target CP molecules and improved sensitivity. After optimization, the chip showed direct, ultrasensitive (as low as 0.2 ng/mL), fast (5 min), and selective detection of CP with a wide concentration range extending from 0.2 ng/mL to 1000 ng/mL. During detection, color changes of the chip were observed by naked eyes without any color display equipment. The recovery of CP was between 94.65 % and 108.70 % in chicken and milk samples.

Association of Preoperative Subchondral Bone Marrow Oedema with Outcomes after Lateral Unicompartmental Knee Arthroplasty.

OBJECTIVE: To determine whether the presence of preoperative subchondral bone marrow oedema (SBME) is associated with inferior outcomes after lateral unicompartmental knee arthroplasty (LUKA). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Orthopaedic Surgery, Chongqing Orthopaedic Hospital of Traditional Chinese Medicine, Chongqing, China, from January 2019 to June 2022. METHODOLOGY: Data on patients treated with LUKA were obtained from the Medical Registry Database. Two groups were made based on the presence and absence of SBME on preoperative magnetic resonance imaging (MRI). The visual analogue scale (VAS), American Knee Society Scores (AKSS), and rate of patient satisfaction were compared between the two groups. RESULTS: A total of 20 patients treated with LUKA were reviewed. The SBME was present in 9 cases and absent in 11 cases. Patients with SBME had inferior scores at preoperative evaluation and at 1, 3, and 6 months postoperatively. However, there was no significant difference between the groups at the 12-month follow-up. Eight (88.9%) patients with SBME were satisfied with the LUKA surgery versus 9 (81.8%) patients without SBME, showing no significant differences between groups. CONCLUSION: Presence of preoperative SBME is associated with inferior functional outcomes after LUKA within six months of follow-up. KEY WORDS: Bone marrow, Oedema, Knee, Arthroplasty, Outcome, Patient satisfaction.

A new resorcylic acid lactone from the endophytic fungus Chaetosphaeronema sp.

A new 14-membered resorcylic acid lactone (RAL14), chaetolactone A (1), along with three known ones (2-4), was obtained from the fermentation of the soil-derived fungus Chaetosphaeronema sp. SSJZ001. Their structures were established based on extensive spectroscopic data analyses (UV, IR, HRESIMS, 1D, and 2D NMR),13C NMR chemical shifts calculations coupled with the DP4+ probability method, theoretical calculations of ECD spectra, as well as X-ray diffraction analysis. All compounds were evaluated for their cytotoxic effects against A549, HO-8910, and MCF-7 cell lines.

Rapid Initiation of Antiretroviral Therapy Under the Treat-All Policy Reduces Loss to Follow-Up and Virological Failure in Routine Human Immunodeficiency Virus Care Settings in China: A Retrospective Cohort Study (2016-2022).

Following the World Health Organization's guidelines for rapid antiretroviral therapy (ART) initiation [≤7 days after human immunodeficiency virus (HIV) diagnosis], China implemented Treat-All in 2016 and has made significant efforts to provide timely ART since 2017. This study included newly diagnosed HIV adults from Tianjin, China, between 2016 and 2022. Our primary outcome was loss to follow-up (LTFU) at 12 months after enrollment. The secondary outcome was 12-month virological failure. The association between rapid ART and LTFU, as well as virological failure, was assessed via Cox regression and logistic regression. A total of 896 (19.1%) of 4688 participants received ART ≤7 days postdiagnosis. The rate of rapid ART has increased from 7.5% in 2016 to 33.3% by 2022. The rapid ART group had an LTFU rate of 3.3%, as opposed to 5.0% in the delayed group. The rapid ART group had a much reduced virological failure rate (0.6% vs. 1.8%). Rapid ART individuals had a reduced likelihood of LTFU [adjusted hazard ratio: 0.65, 95% confidence intervals (CI): 0.44-0.96] and virological failure (adjusted odds ratio: 0.35, 95% CI: 0.12-0.80). The real-world data indicated that rapid ART is practicable and beneficial for Chinese people with HIV, providing evidence for its widespread implementation and scaling up.

An endometrial biomimetic extracellular matrix (ECM) for enhanced endometrial regeneration using hyaluronic acid hydrogel containing recombinant human type III collagen.

Endometrial injury poses a significant challenge in tissue regeneration, with type III collagen (COL III) playing a pivotal role in maintaining endometrial integrity and facilitating repair. Our study explored the utility of recombinant human type III collagen (RHC) as an intervention for endometrial damage. To address the challenges associated with the inherent instability and rapid degradation of COL III in vivo, we developed an RHC-HA hydrogel by conjugating RHC with hyaluronic acid (HA), thus ensuring a more stable and sustained delivery. Our findings suggested that the RHC-HA hydrogel significantly promoted endometrial regeneration and restored fertility. The hydrogel facilitated prolonged retention of RHC in the uterus, leading to a substantial improvement in the repair process. The synergistic interaction between RHC and HA greatly enhances cell proliferation and adhesion, surpassing the efficacy of HA or RHC alone. Additionally, the RHC-HA hydrogel demonstrated notable anti-fibrotic effects, which are crucial for preventing abnormalities during endometrial healing. These findings suggested that the RHC-HA hydrogel presented a therapeutic strategy in the treatment of uterine endometrial injuries, which may improve female reproductive health.

Oleanane and 30-noroleanane triterpenoids from the roots of Paeonia lactiflora.

An investigation of EtOAc extract from the roots of Paeonia lactiflora yielded three new 30-noroleanane triterpenoids paeonenoides L-N (1-3) and one new oleanane triterpenoid paeonenoide O (4) together with 7 known compounds (5-11). Extensive spectrographic experiments were applied to identify the structures of 1-4, and their absolute configurations were unambiguously determined by theoretical calculations of ECD spectra, as well as the single-crystal X-ray diffraction analysis. Compounds 8, 9 and 10 were isolated from the Paeonia genus for the first time. Moreover, compounds 8, 9 and 11 showed inhibitory activities against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages with the IC50 values of 72. 17 ± 4.74, 30.02 ± 2.03 and 28.34 ± 1.85 µM, respectively.