Deep Red Light Driven Hydrogen Evolution by Heterojunction Polymer Dots for Diabetic Wound Healing.

We describe small heterojunction polymer dots (Pdots) with deep-red light catalyzed H2 generation for diabetic skin wound healing. The Pdots with donor/acceptor heterojunctions showed remarkably enhanced photocatalytic activity as compared to the donor or acceptor nanoparticles alone. We encapsulate the Pdots and ascorbic acid into liposomes to form Lipo-Pdots nanoreactors, which selectively scavenge •OH radicals in live cells and tissues under 650 nm light illumination. The antioxidant capacity of the heterojunction Pdots is ~10 times higher than that of the single-component Pdots described previously. Under a total light dose of 360 J/cm2, the Lipo-Pdots nanoreactors effectively scavenged •OH radicals and suppressed the expression of pro-inflammatory cytokines in skin tissues, thereby accelerating the healing of skin wounds in diabetic mice. This study provides a feasible solution for safe and effective treatment of diabetic foot ulcers.

Liquid-liquid phase separation of TZP promotes PPK-mediated phosphorylation of the phytochrome A photoreceptor.

Phytochrome A (phyA) is the plant far-red (FR) light photoreceptor and plays an essential role in regulating photomorphogenic development in FR-rich conditions, such as canopy shade. It has long been observed that phyA is a phosphoprotein in vivo; however, the protein kinases that could phosphorylate phyA remain largely unknown. Here we show that a small protein kinase family, consisting of four members named PHOTOREGULATORY PROTEIN KINASES (PPKs) (also known as MUT9-LIKE KINASES), directly phosphorylate phyA in vitro and in vivo. In addition, TANDEM ZINC-FINGER/PLUS3 (TZP), a recently characterized phyA-interacting protein required for in vivo phosphorylation of phyA, is also directly phosphorylated by PPKs. We reveal that TZP contains two intrinsically disordered regions in its amino-terminal domain that undergo liquid-liquid phase separation (LLPS) upon light exposure. The LLPS of TZP promotes colocalization and interaction between PPKs and phyA, thus facilitating PPK-mediated phosphorylation of phyA in FR light. Our study identifies PPKs as a class of protein kinases mediating the phosphorylation of phyA and demonstrates that the LLPS of TZP contributes significantly to more production of the phosphorylated phyA form in FR light.

Evaluation of Osteoarthritis Disease Burden in China During 1990-2019 and Forecasting Its Trend Over the Future 25 Years.

OBJECTIVE: This study aimed to estimate the temporal trend of osteoarthritis (OA) burden in China by age, sex, and joint sites from 1990 to 2019 and predict the long-term trend over the next 25 years. METHODS: Using data from the Global Burden of Disease Study 2019, we estimated incident cases, prevalent cases, disability-adjusted life years (DALYs) of OA, and DALYs of OA attributed to high body mass index (BMI), as well as corresponding age-standardized rates (ASRs) for aforementioned indicies. Estimated annual percentage change (EAPC) and Nordpred age-period-cohort model were used to describe temporal trend changes and predict future disease burden. RESULTS: From 1990 to 2019, the ASR of OA incidence increased from 472.53 per 100,000 to 509.84 per 100,000 people (EAPC: 0.36, 95% confidence interval [CI] 0.29-0.44); the ASR of OA prevalence increased from 5,880.58 per 100,000 to 6,330.06 per 100,000 people (EAPC 0.35, 95% CI 0.28-0.42); the ASR of OA DALYs increased from 206.38 per 100,000 to 224.78 per 100,000 people (EAPC 0.40, 95% CI 0.32-0.48). The ASR of OA DALYs attributed to high BMI increased rapidly, especially in men and patients with hip OA. Projections suggest an increasing trend in the incidence, prevalence, and DALYs of OA from 2019 to 2044, with the prevalent cases and DALYs of OA in China expected to increase by approximately 1.5 times over the next 25 years. CONCLUSION: The disease burden of OA has increased in China over the past 30 years and is expected to continue rising over the next 25 years.

Biomolecular condensation orchestrates clathrin-mediated endocytosis in plants.

Clathrin-mediated endocytosis is an essential cellular internalization pathway involving the dynamic assembly of clathrin and accessory proteins to form membrane-bound vesicles. The evolutionarily ancient TSET-TPLATE complex (TPC) plays an essential, but ill-defined role in endocytosis in plants. Here we show that two highly disordered TPC subunits, AtEH1 and AtEH2, function as scaffolds to drive biomolecular condensation of the complex. These condensates specifically nucleate on the plasma membrane through interactions with anionic phospholipids, and facilitate the dynamic recruitment and assembly of clathrin, as well as early- and late-stage endocytic accessory proteins. Importantly, condensation promotes ordered clathrin assemblies. TPC-driven biomolecular condensation thereby facilitates dynamic protein assemblies throughout clathrin-mediated endocytosis. Furthermore, we show that a disordered region of AtEH1 controls the material properties of endocytic condensates in vivo. Alteration of these material properties disturbs the recruitment of accessory proteins, influences endocytosis dynamics and impairs plant responsiveness. Our findings reveal how collective interactions shape endocytosis.

Evaluation of the efficacy of a sunscreen containing ultra-long UVA1 and other UVR broad-spectrum filters on skin barrier protection and melanin content reduction in Chinese adults: A single-center study.

Background and Aims: The protection for ultra-long UVA1 is lacked in the market, posing potential damage from ultra-long UVA1 irradiation. The study aims to evaluate the efficacy of a sunscreen containing multiple components, especially Mexoryl® 400 for improving skin barrier function and reducing melanin content. Methods: This single-center study included adults with sensitive and normal skin in China in November 2022. Participants received the test sunscreen for 4 weeks. Melanin and hemoglobin content, sebum secretion skin hydration, and trans-epidermal water loss were evaluated at T0d, T7d, and T28d. The self-assessment was done at T15min, T7d, and T28d. Results: Sixty participants were included, including 30 self-claimed sensitive skin in the sunscreen group. The sunscreen demonstrated significant improvements in skin parameters. Skin redness reduced by 9.84% at T28d, sebum content in the forehead area decreased by 22.70% at T28d, and skin stratum corneum hydration increased by 38.44% at T28d, p < 0.001 respectively. Most notably, skin melanin content significantly reduced by 13.49% after 4 weeks' usage (p < 0.001). No adverse reactions were reported in either group. Conclusions: The study sunscreen improved the skin condition by decreasing the melanin content, regulating skin barrier function, and achieving a balance of skin hydration and sebum secretion.

Efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate for improving sensitive skin symptoms.

BACKGROUND: Sensitive skin is a common condition affecting a significant proportion of the population, and there is a growing demand for effective and safe management. AIM: To evaluate the efficacy and safety of a cream containing panthenol, prebiotics, and probiotic lysate as an optimal care for facial sensitive skin. METHODS: A total of 110 participants (64 in group A and 46 in group B) with facial sensitive skin applied the cream twice daily for 28 days. Group A evaluated their sensitive skin, product efficacy, and product use experience at D0 (15 min), D1, D14, and D28. In group B, skin barrier function-related indicators were measured at baseline and on D1, D7, D14, and D28. Dermatologists evaluated tolerance for all participants. RESULTS: After 28 days of use, in group A, 100% of participants reported mildness and comfort with product use. Participants demonstrated significant improvements in skin barrier function-related indicators, including increased stratum corneum moisture content, reduced erythema index, elevated sebum content, decreased trans-epidermal water loss, and diminished skin redness parameter a* value (all p < 0.05). Dermatologist evaluations revealed excellent tolerance among all participants. CONCLUSION: The panthenol-enriched cream with prebiotics and probiotic lysate exhibited substantial clinical efficacy in ameliorating facial sensitive skin conditions, coupled with a high safety profile.

Risk Factors for Seizures After Titanium Cranioplasty: Five-Year Experience from a Single Institution.

OBJECTIVE: Seizures are one of the complications that can occur after cranioplasty (CP). In some regions, titanium mesh remains the material of choice for CP. However, risk factors for seizures after titanium CP have been less studied. The purpose of this study was to identify potential risk factors for early seizures (≤7 days) and late seizures (>8 days) after titanium CP in a single institution. METHODS: A retrospective review was conducted of 241 consecutive patients who received titanium CP at the First Affiliated Hospital of Harbin Medical University from January 2016 to December 2020. Univariate and multivariable logistic regression analyses were performed to determine the independent risk factors for new-onset seizures after titanium CP. RESULTS: Fifteen patients (6.22%) experienced early post-CP seizures, and late post-CP seizures were observed in 81 patients (33.61%). A flaccid concave cranial defect (P = 0.042) was associated with early post-CP seizures, whereas hypertension (P < 0.001) was the only significant predictor for late seizures after titanium CP. CONCLUSIONS: Seizure is a common complication after titanium CP, especially in patients who do not receive prophylactic antiepileptic drugs before the procedure. Risk factors for new-onset seizures at different periods after titanium CP were found to be different. In addition, radiologic factors before titanium CP may play a role in early new-onset seizures after titanium CP and should not be ignored.

Comprehensive assessment of the efficacy and safety of a clay mask in oily and acne skin.

BACKGROUND: Oily skin, characterized by excessive sebum production, can lead to acne and have psychosocial impacts due to changes in appearance. Recent research has shown interest in treatments for oil control, with kaolin and bentonite emerging as promising options. Despite their potential, comprehensive studies on these ingredients are still in the nascent stages. AIM: This study aimed to assess the efficacy of a clay mask (La Roche-Posay Effaclar Sebo-Controlling Mask) in reducing skin oiliness and acne, and its safety for use. METHODS: In this study, 75 adults with oily or combination skin were enrolled and provided with a clay mask for twice-weekly use over 4 weeks. Clinical assessments, using instruments like Sebumeter, Vapometer, and Corneometer, were conducted at baseline, and after 1, 2, and 4 weeks, evaluating acne lesions, skin irritation, sebum content, and skin hydration. Participant self-assessment questionnaires were also utilized for subjective evaluation. Statistical analyses were performed accordingly. RESULTS: The study revealed significant improvements in acne-related outcomes, sebum content, skin evenness, stratum corneum water content, and transepidermal water loss following the application of the clay mask. Pore area and porphyrin area showed no significant changes. Tolerance assessment showed reduced dryness and irritation, with self-assessment indicating high product acceptability and perceived oil control effectiveness. CONCLUSION: This study demonstrated the clay mask's efficacy in managing acne and oily skin, improving hydration and texture. Significant improvements in skin parameters and high product safety were observed, supporting its suitability.

Site-Specific Modification of Single Domain Antibodies by Enzyme-Immobilized Magnetic Beads.

Nanobodies as imaging agents and drug conjugates have shown great potential for cancer diagnostics and therapeutics. However, site-specific modification of a nanobody with microbial transglutaminase (mTGase) encounters problems in protein separation and purification. Here, we describe a facile yet reliable strategy of immobilizing mTGase onto magnetic beads for site-specific nanobody modification. The mTGase immobilized on magnetic beads (MB-mTGase) exhibits catalytic activity nearly equivalent to that of the free mTGase, with good reusability and universality. Magnetic separation simplifies the protein purification step and reduces the loss of nanobody bioconjugates more effectively than size exclusion chromatography. Using MB-mTGase, we demonstrate site-specific conjugation of nanobodies with fluorescent dyes and polyethylene glycol molecules, enabling targeted immunofluorescence imaging and improved circulation dynamics and tumor accumulation in vivo. The combined advantages of MB-mTGase method, including high conjugation efficiency, quick purification, less protein loss, and recycling use, are promising for site-specific nanobody functionalization and biomedical applications.

The PIF1/PIF3-MED25-HDA19 transcriptional repression complex regulates phytochrome signaling in Arabidopsis.

Light signals are perceived by photoreceptors, triggering the contrasting developmental transition in dark-germinated seedlings. Phytochrome-interacting factors (PIFs) are key regulators of this transition. Despite their prominent functions in transcriptional activation, little is known about PIFs' roles in transcriptional repression. Here, we provide evidence that histone acetylation is involved in regulating phytochrome-PIFs signaling in Arabidopsis. The histone deacetylase HDA19 interacts and forms a complex with PIF1 and PIF3 and the Mediator subunit MED25. The med25/hda19 double mutant mimics and enhances the phenotype of pif1/pif3 in both light and darkness. HDA19 and MED25 are recruited by PIF1/PIF3 to the target loci to reduce histone acetylation and chromatin accessibility, providing a mechanism for PIF1/PIF3-mediated transcriptional repression. Furthermore, MED25 forms liquid-like condensates, which can compartmentalize PIF1/PIF3 and HDA19 in vitro and in vivo, and the number of MED25 puncta increases in darkness. Collectively, our study establishes a mechanism wherein PIF1/PIF3 interact with HDA19 and MED25 to mediate transcriptional repression in the phytochrome signaling pathway and suggests that condensate formation with Mediator may explain the distinct and specific transcriptional activity of PIF proteins.

Near-Infrared II Semiconducting Polymer Dots: Chain Packing Modulation and High-Contrast Vascular Imaging in Deep Tissues.

Fluorescence imaging in the second near-infrared (NIR-II) window has attracted considerable interest in investigations of vascular structure and angiogenesis, providing valuable information for the precise diagnosis of early stage diseases. However, it remains challenging to image small blood vessels in deep tissues because of the strong photon scattering and low fluorescence brightness of the fluorophores. Here, we describe our combined efforts in both fluorescent probe design and image algorithm development for high-contrast vascular imaging in deep turbid tissues such as mouse and rat brains with intact skull. First, we use a polymer blending strategy to modulate the chain packing behavior of the large, rigid, NIR-II semiconducting polymers to produce compact and bright polymer dots (Pdots), a prerequisite for in vivo fluorescence imaging of small blood vessels. We further developed a robust Hessian matrix method to enhance the image contrast of vascular structures, particularly the small and weakly fluorescent vessels. The enhanced vascular images obtained in whole-body mouse imaging exhibit more than an order of magnitude improvement in the signal-to-background ratio (SBR) as compared to the original images. Taking advantage of the bright Pdots and Hessian matrix method, we finally performed through-skull NIR-II fluorescence imaging and obtained a high-contrast cerebral vasculature in both mouse and rat models bearing brain tumors. This study in Pdot probe development and imaging algorithm enhancement provides a promising approach for NIR-II fluorescence vascular imaging of deep turbid tissues.

Emerging roles of phase separation in plant transcription and chromatin organization.

Transcription is a core step in gene expression. Regulation of transcription is achieved at the level of transcription machinery, local chromatin environment as well as higher-order chromatin organization. Our understanding of transcriptional regulation was advanced by recent introduction of transcription and chromatin-associated condensates, which typically arise via phase separation of proteins and nucleic acids. While studies from mammalian cells are unveiling the mechanisms of phase separation in transcription regulation, those in plants further broaden and deepen our understanding of this process. In this review, we discuss recent progress in plants how phase separation operates in RNA-mediated chromatin silencing, transcription activity, and chromatin compartmentalization.

Time-series prediction and detection of potential pathogens in bloodstream infection using mcfDNA sequencing.

Introduction: Next-generation sequencing of microbial cell free DNA (mcfDNA-seq) has emerged as a promising diagnostic method for blood stream infection (BSI) and offers the potential to detect pathogens before blood culture. However, its application is limited by a lack of clinical validation. Methods: We conducted sequential mcfDNA-seq on blood samples from ICU participants at high risk of BSI due to pneumonia, or intravascular catheterization; and explored whether mcfDNA-seq could diagnose and detect pathogens in advance of blood culture positivity. Blood culture results were used as evaluation criteria. Results: A total of 111 blood samples were collected during the seven days preceding and on the day of onset of 16 BSI episodes from 13 participants. The diagnostic and total predictive sensitivity of mcfDNA-seq were 90% and 87.5%, respectively. The proportion of pathogenic bacteria was relatively high in terms of both diagnosis and prediction. The reads per million of etiologic agents trended upwards in the days approaching the onset of BSI. Discussion: Our work found that mcfDNA-seq has high diagnostic sensitivity and could be used to identify pathogens before the onset of BSI, which could help expand the clinical application of mcfDNA-seq.

[Nitrogen Metabolism and Flora Characteristics of Bacteria Algae Complex System].

In order to denitrify the urban tail water deeply and control the eutrophication of surface water, the molecular biology methods were used to study the nitrogen metabolism performance of the denitrification complex flora and the algal-bacteria symbiotic system. The results showed that the nitrogen metabolism complex flora was high ammonification and denitrification performance. The removal effect of ammonia nitrogen of group JZ was very well in urban tailwater, and the degradation rate was as high as 95%. The removal effect of total nitrogen of group JZ was better than that of group J in the experimental water distribution. High-throughput sequencing showed that the main dominant flora and proportion of group J were Firmicutes 44.53%, Proteobacteria 43.41%, Actinobacteria 5.37%, Bacteroidetes 3.04%, and Chloroflexi 1.35%. The main dominant bacterial groups in the group JZ were 33.89% Cyanobacteria, 25.34% Chloroflexi, 19.38% Proteobacteria, 10.02% Firmicutes, and 4.20% Acidobacteria. The dominant species in group J were compared with those in group JZ; the proportions were 82% and 18% in Firmicutes, 69% and 31% in Proteobacteria, 1% and 99% in Cyanobacteria, 5.1% and 95% in Chloroflexi, 73% and 27% in Actinobacteria. It was concluded that the removal effect of ammonia nitrogen of group JZ was high in the urban tailwater. With the addition and growth of Micrococcus in group J, the nitrogen metabolism flora in group JZ changed accordingly, so as to adapt to the environment in which the dominant algae formed. It forms a new nitrogen metabolism system of bacteria and algae with Micrococcus. This research provides a theoretical and data basis for the application of algal-bacterial co-metabolism systems.

Near Infrared-Absorbing Nanoparticle-Mediated Endovascular Photothermal Precision Embolization of Tumor Feeding Vessels for Starvation Treatment.

Photothermal therapy has attracted enormous attention as an efficient treatment modality in cancer ablation but still encounters a major bottleneck due to the limited penetration depth of light inside tissues. To overcome the challenge of deep tissue penetration, we present a strategy of endovascular photothermal precision embolization (EPPE), which employs an endovascular optical fiber to induce local embolization only in the entrance of feeding vessels through photothermal heating for the purpose of fully blocking the blood supply of the whole tumor. In EPPE, we apply a highly efficient and biocompatible photothermal agent, i.e., near-infrared (NIR)-light-absorbing diketopyrrolopyrrole-dithiophene-based nanoparticle, which exhibits a high cell-killing efficacy at a concentration of 200 µg/mL using 808 nm laser irradiation of 0.5 W/cm2 within 5 min in both 2D cell culture and a 3D tumor spheroid model. We verify the feasibility of EPPE in an ex vivo organ-structured recellularized liver model and further confirm the in vivo efficacy of the photothermal treatment in a rat liver model. The photothermal treatment combined with the embolization effect holds promise to serve as an effective starvation therapy to treat tumors of varying sizes and locations.

Bone marrow lesions in osteoarthritis: From basic science to clinical implications.

Osteoarthritis (OA) is the most prevalent musculoskeletal disease characterized by multiple joint structure damages, including articular cartilage, subchondral bone and synovium, resulting in disability and economic burden. Bone marrow lesions (BMLs) are common and important magnetic resonance imaging (MRI) features in OA patients. Basic and clinical research on subchondral BMLs in the pathogenesis of OA has been a hotspot. New evidence shows that subchondral bone degeneration, including BML and angiogenesis, occurs not only at or after cartilage degeneration, but even earlier than cartilage degeneration. Although BMLs are recognized as important biomarkers for OA, their exact roles in the pathogenesis of OA are still unclear, and disputes about the clinical impact and treatment of BMLs remain. This review summarizes the current basic and clinical research progress of BMLs. We particularly focus on molecular pathways, cellular abnormalities and microenvironmental changes of subchondral bone that contributed to the formation of BMLs, and emphasize the crosstalk between subchondral bone and cartilage in OA development. Finally, potential therapeutic strategies targeting BMLs in OA are discussed, which provides novel strategies for OA treatment.

Efficacy and safety of vapocoolant spray for vascular puncture in children and adults: A systematic review and meta-analysis.

OBJECTIVE: The aim was to evaluate the effectiveness and safety of the vapocoolants for vascular puncture in children and adults. METHOD: The search was carried out in PubMed, Web of Science, Embase and The Cochrane Library, from inception to March 2022. Randomized controlled trials comparing vapocoolants to control conditions for participants received intravenous cannulation or arterial puncture were included. Two reviewers independently performed selection of studies, data extraction, and assessment of risk of bias. The analysis was performed using fixed or random-effects model with mean differences or standardized mean difference and risk ratios. RESULTS: A total of 25 studies involving 3143 participants were included. Compared with control conditions, vapocoolants may not decrease the pain of patients with arterial puncture (SMD = -0.36, 95% CI = -0.92 to -0.19, P = 0.20), but may more effectively relieve pain for adults received vein puncture (SMD = -0.65, 95% CI = -0.85 to -0.45, P < 0.00001). The application of vapocoolant increased the procedural difficulty of medical personnel (RR = 2.49, 95% CI = 1.62 to 3.84, P<0.000 1) and participants were more willing to use the spray in the future (RR = 1.88, 95% CI = 1.34 to 2.64, P = 0.0002). There was no significant difference for the first attempt success rate of the procedure and the occurrence of adverse events. CONCLUSIONS: Vapocoolant spray may relieve pain in adults received vein puncture and cannot cause severe side effects, but is ineffective in children. It also had no effect on patients with arterial puncture. In addition, the application of spray increases procedural difficulties for medical professionals, but does not decrease first attempt success rate, and many patients would like to use the spray again for pain relief in the future. Thus, more rigorous and large-scale studies are needed to determine its effectiveness in vascular access.

Photoswitchable semiconducting polymer dots for pattern encoding and superresolution imaging.

Two photoswitchable semiconducting polymers were synthesized by covalently incorporating photochromic dithienylethene (DTE) into the main chains. Small size polymer dots (Pdots) were prepared and showed dynamic photoswitching upon alternate light irradiation. By virtue of the tunable photoswitching properties, effective pattern encoding and superresolution imaging with a resolution of up to about 30 nm were achieved.