MCM8 interacts with DDX5 to promote R-loop resolution.

MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.

Trps1 predicts poor prognosis in advanced high grade serous ovarian carcinoma.

TRPS1 is aberrantly expressed in a variety of tumors, including breast, prostate, and gastric cancers, and is strongly associated with tumorigenesis or prognosis. However, the role of TRPS1 in high grade serous ovarian carcinoma (HGSC) is unknown. We investigated the relationship between TRPS1 expression and clinicopathology in HGSC patients. The tumor-related regulatory mechanisms of TRPS1 was explored through in vivo and vitro experiments. The results showed that TRPS1 was highly expressed in HGSC compared to normal tissues. It was also linked to the cell proliferation index Ki67 and poor prognosis. In vivo experiments showed that knockdown of TRPS1 could inhibit tumor growth. In vitro experiments, knockdown of TRPS1 inhibited the proliferation of ovarian cancer cells. TRPS1 exerted its regulatory role as a transcription factor, binding to the PSAT1 promoter and promoting the expression of PSAT1 gene. Meanwhile, PSAT1 was positively correlated with CCND1 expression. These results suggest that TRPS1 affects HGSC proliferation and cell cycle by regulating PSAT1 and thus CCND1 expression.

Organic-Hydrochloride-Modified ZnO Electron Transport Layer for Efficient Defect Passivation and Stress Release in Rigid and Flexible all Inorganic Perovskite Solar Cells.

All inorganic CsPbI2Br perovskite (AIP) has attracted great attention due to its excellent resistance against thermal stress as well as the remarkable capability to deliver high-voltage output. However, CsPbI2Br perovskite solar cells (PeSCs) still encounter critical challenges in attaining both high efficiency and mechanical stability for commercial applications. In this work, formamidine disulfide dihydrochloride (FADD) modified ZnO electron transport layer (ETL) has been developed for fabricating inverted devices on either rigid or flexible substrate. It is found that the FADD modification leads to efficient defects passivation, thereby significantly reducing charge recombination at the AIP/ETL interface. As a result, rigid PeSCs (r-PeSCs) deliver an enhanced efficiency of 16.05% and improved long-term thermal stability. Moreover, the introduced FADD can regulate the Young's modulus (or Derjaguin-Muller-Toporov (DMT) modilus) of ZnO ETL and dissipate stress concentration at the AIP/ETL interface, effectively restraining the crack generation and improving the mechanical stability of PeSCs. The flexible PeSCs (f-PeSCs) exhibit one of the best performances so far reported with excellent stability against 6000 bending cycles at a curvature radius of 5 mm. This work thus provides an effective strategy to simultaneously improve the photovoltaic performance and mechanical stability.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

Single femtosecond pulse writing of a bifocal lens.

In this Letter, a method for the fabrication of bifocal lenses is presented by combining surface ablation and bulk modification in a single laser exposure followed by the wet etching processing step. The intensity of a single femtosecond laser pulse was modulated axially into two foci with a designed computer-generated hologram (CGH). Such pulse simultaneously induced an ablation region on the surface and a modified volume inside the fused silica. After etching in hydrofluoric acid (HF), the two exposed regions evolved into a bifocal lens. The area ratio (diameter) of the two lenses can be flexibly adjusted via control of the pulse energy distribution through the CGH. Besides, bifocal lenses with a center offset as well as convex lenses were obtained by a replication technique. This method simplifies the fabrication of micro-optical elements and opens a highly efficient and simple pathway for complex optical surfaces and integrated imaging systems.

Selectively Transport and Removal of Fluoride Ion by Pillar[5]Arene Polymer-Filled Nanochannel Membrane.

Excess fluoride ions in groundwater accumulate through the roots of crops, affecting photosynthesis and inhibiting their growth. Long-term bioaccumulation also threatens human health because it is poorly degradable and toxic. Currently, one of the biggest challenges is developing a unique material that can efficiently remove fluoride ions from the environment. The excellent properties of functionalized pillar[5]arene polymer-filled nanochannel membranes were explored to address this challenge. Constructing a multistage porous nanochannel membrane, consisting of microscale etched nanochannels and nanoscale pillar[5]arene cross-linked polymer voids. A fluoride removal rate of 0.0088 mmol ⋅ L-1 ⋅ min-1 was achieved. Notably, this rate surpassed the rates observed with other control ions by a factor of 6 to 8.8. Our research provides a new direction for developing water fluoride ion removal materials.

Efficient Adsorption and Elimination of Tm3+ For Enhanced Seed Germination Using Pillar[5]Arene Polymer.

While rare earth elements (REEs) are essential for modern technology, their production methods raise concerns for agriculture. Researchers are now exploring ways to control and recycle REEs pollution, aiming to minimize agricultural impacts and potentially even develop methods to utilize these elements for improved crop yields. Regarding this issue, a new type of pillar[5]arene polymer (Pol-P[5]-BTZP) has been designed and synthesized by click reaction to enhance the efficiency of adsorption and recovery of rare earth metals. This polymer incorporates the unique structure of 2,6-di-1,2,3-triazolyl-pyridine. The results of various analyses revealed that Pol-P[5]-BTZP exhibits excellent thermal stability, a high specific surface area, and well-distributed networks of micropores and mesoporous structures. The adsorption capacity of Pol-P[5]-BTZP for Tm3+, a representative REE, was evaluated using the Langmuir and Freundlich isothermal adsorption models with a maximum adsorption capacity (Qmax) of 127.71 mg/g. Furthermore, the versatility of Pol-P[5]-BTZP in adsorption and recovering various REEs was tested. In addition to its adsorption capabilities, the potential of Pol-P[5]-BTZP for rare earth recovery and reuse was assessed through experiments on the impact of Tm3+ and La3+ on seed germination. These experiments demonstrated the wide-ranging applicability of Pol-P[5]-BTZP in recovering and reusing REEs for green agriculture.

C-Me-graphene: an ideal two-dimensional nodal line semimetal with ultrahigh Young's modulus.

Nodal line semimetal (NLSM) has become a captivating medium for studying varieties of novel quantum phenomena. Here, based on first-principles calculations, we identify a square compound lattice (SCL) structure, namely C-Me-graphene, featuring a NLSM, wherein the nodal line of this configuration resides precisely at the Fermi energy without any extraneous bands in the vicinity, manifesting the quintessential characteristics of an ideal NLSM. As a corollary, utilizing symmetry analysis, we propose that nodal lines can be generated by exploiting the two-dimensional (2D) SCL of carbon. This is because the SCL not only satisfies time-reversal symmetry and inversion symmetry but also conforms to glide mirror symmetry. Additionally, this structure reveals remarkable mechanical attributes, exemplifying the highest Young's modulus within the realm of 2D materials, second only to graphene. Our work not only identifies an ideal carbon-based NLSM but also advances a scheme for crafting NLSMs, which would greatly enrich topological materials with exotic properties.

The effect of pterygium on front and back corneal astigmatism and aberrations in natural-light and low-light conditions.

BACKGROUND: To investigate the effect of different sizes of pterygium on the front and back corneal topography, refractive changes and aberrations in natural-light and low-light conditions. METHODS: Sixty subjects with unilateral primary nasal pterygium were enrolled in this study. All the patients' uncorrected, best spectacle-corrected visual acuity, corneal topographic aberration data in 3 mm and 7 mm areas were collected. The pterygium size was evaluated by the slit-lamp photography and Sirius Scheimpflug Analyzer. RESULTS: The front topographic astigmatism values, corneal total aberrations, and higher-order aberrations in 3 mm and 7 mm areas were higher in the pterygium group than those in the control group. The pterygium horizontal length and thickness were moderately to strongly correlated with astigmatism and RMS of aberrations, while pterygium vertical length showed no or just mild correlation with the corneal astigmatism and aberrations. Compared to the readings in 3 mm area, the front and back corneal astigmatism and aberrations were larger in 7 mm area. CONCLUSIONS: Pterygium led to visual impairment by inducing astigmatism and aberrations. In low-light condition, the visual function worsened due to increased corneal astigmatism values and aberrations.

The inhibition of MARCO by PolyG alleviates pulmonary fibrosis via regulating mitochondrial function in a silicotic rat model.

Silicon dioxide (SiO2)-induced pulmonary fibrosis is potentially associated with the impairment of mitochondrial function. Previous research found that inhibition of macrophage receptor with collagenous structure (MARCO) could alleviate particle-induced lung injury by regulating phagocytosis and mitigating mitochondrial damage. The present study aims to explore the underlying anti-fibrosis mechanism of polyguanylic acid (PolyG, MARCO inhibitor) in a silicotic rat model. Hematoxylin and eosin and Masson staining were performed to visualize lung tissue pathological changes. Confocal microscopy, transmission electron microscope, western blot analysis, quantitative real-time PCR (qPCR), and adenosine triphosphate (ATP) content assay were performed to evaluate collagen content, mitochondrial function, and morphology changes in SiO2-induced rat pulmonary fibrosis. The results suggested that SiO2 exposure contributed to reactive oxygen species aggregation and the reduction of respiratory complexes and ATP synthesis. PolyG treatment could effectively reduce MARCO expression and ameliorate lung injury and fibrosis by rectifying the imbalance of mitochondrial respiration and energy synthesis. Furthermore, PolyG could maintain mitochondrial homeostasis by promoting peroxisome proliferator-activated receptor-coactivator 1 α (PGC1α)-mediated mitochondrial biogenesis and regulating fusion and fission. Together, PolyG could ameliorate SiO2-induced pulmonary fibrosis via inhibiting MARCO to protect mitochondrial function.

The "4+4" Medical Doctor (MD) Pilot Program at PUMC: Implementation, Performance, and Prospects.

Peking Union Medical College (PUMC) launched the "4+4" Medical Doctor (MD) pilot program in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" MD pilot class at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "Medicine + X" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, and reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.

Structural Phase Separation of Membranes and Fibers.

Lipid membranes interact with protein filaments on a superstructural level such that they may colocalize or spatially segregate in a living cell, whereas higher-order organization of membranes and fibers is less well explored in artificial systems. Herein, we report on the structural separation of a dispersed, membranous phase and a continuous, fibrous phase in a synthetic system. Systematic characterization of its thermodynamics and kinetics uncovers a physical principle governing phase separation: Interlamellar repulsion, favoring expansion of the membranous phase, is balanced by fibrous network elasticity, preferring the opposite. A direct consequence of this principle is the spatial addressability of the phase separation, preferably localized to soft regions of the fibrous network. Guided by this principle, we design a fibrous network with different spatial heterogeneity to modulate the phase separation, realizing a "memory" effect, patterned separation, and gradient separation. The current spatially addressable phase separation is in great contrast to the conventional ones, in which nucleation is difficult to predict or control. The fact that the membranous and fibrous phases compete for space has implications for the intracellular interactions between endoplasmic reticulum membranes and cytoskeletal filaments.

The Antioxidant Properties, Metabolism, Application and Mechanism of Ferulic Acid in Medicine, Food, Cosmetics, Livestock and Poultry.

Ferulic acid is a ubiquitous ingredient in cereals, vegetables, fruits and Chinese herbal medicines. Due to the ferulic phenolic nucleus coupled to an extended side chain, it readily forms a resonant-stable phenoxy radical, which explains its potent antioxidant potential. In addition, it also plays an important role in anti-cancer, pro-angiogenesis, anti-thrombosis, neuroprotection, food preservation, anti-aging, and improving the antioxidant performance of livestock and poultry. This review provides a comprehensive summary of the structure, mechanism of antioxidation, application status, molecular mechanism of pharmacological activity, existing problems, and application prospects of ferulic acid and its derivatives. The aim is to establish a theoretical foundation for the utilization of ferulic acid in medicine, food, cosmetics, livestock, and poultry.

[Therapeutic idea for post-stroke foot inversion with Cixi Tongshu method combined with rehabilitation training].

Based on the function of xi-cleft points and shu-streams points and in association with the anatomic structure where the acupoints are located, Cixi (stimulating meridian qi at xi-cleft points) is used for regulating the physical appearance, while Tongshu (promoting the qi circulation of shu-stream points) is for regulating the spirit. The depth and direction of needle insertion are controlled and deqi is determined by muscle twitching so as to relax the muscles. Rehabilitation training is combined to restore the foot proprioceptive sensibility. The above comprehensive method co-works on correcting post-stroke foot inversion and recovering walking ability in the patients.

Risk factors for malnutrition in patients with diabetic foot ulcer and its association with prolonged length of hospitalization.

PURPOSE: The study was designed to investigate the occurrence and risk factors of malnutrition in diabetic foot ulcers (DFU) patients and examine the association between malnutrition and length of stay (LOS). METHODS: This observational study included DFU hospitalized patients in two campuses of a hospital from January 2021 to June 2023. The diagnosis standard of malnutrition was established by using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Patients were followed up to ascertain the length of hospitalization, and hospital stays longer than 17 days were considered as prolonged LOS. To explore the risk factors of malnutrition and the association between malnutrition and LOS, univariate and multivariate logistic regression analyses were performed. RESULTS: Overall 219 DFU patients were enrolled, malnutrition was identified in 38.36% of patients according to GLIM criteria, and 92 patients (42%) were recognized as prolonged LOS. Logistic regression analyses showed that BMI (P <0.001), Alb (P = 0.002), HbA1c (P <0.001), ulcer infection (P <0.001), LOS (P = 0.010), and ABI (P = 0.024) were independent risk factors for malnutrition. Besides, malnutrition by GLIM criteria was closely related to prolonged LOS and malnourished DFU patients were 2.857 times (95% CI, 1.497-5.450; P = 0.001) likely to present prolonged LOS than that of normal nutrition. CONCLUSION: Malnutrition was considered to be extremely prevalent in DFU patients and was associated with approximately three times higher likelihood of prolonged LOS. Implementing and disseminating the diagnostic criteria during routine practice is crucial, given the predictive efficacy of GLIM criteria.

Acute kidney injury during autologous stem cell transplantation in light chain amyloidosis with kidney involvement and their impact on prognosis.

Acute kidney injury (AKI) is a complication related to important organ dysfunction during autologous stem cell transplantation (ASCT) in light chain (AL) amyloidosis. This study aims to validate the risk factors of AKI during different periods of ASCT and the impact of AKI on long-term outcomes. 302 patients with AL amyloidosis and kidney involvement who underwent ASCT were included. The procedures from stem cell mobilization to 30 days after transplantation were categorized into four periods: Period 0 (stem cell mobilization and harvest), Period 1 (preparation), Period 2 (conditioning and transplantation), and Period 3 (engraftment). The incidence of AKI during ASCT was 27.15% (0.66% in Period 0, 6.62% in Period 1, 15.23% in Period 2, and 6.95% in Period 3). The major causes of AKI were capillary leak syndrome in Period 0, ganciclovir or sulfamethoxazole/trimethoprim in Period 1, high-dose melphalan in Period 2, and engraftment syndrome in Period 3. AKI in different periods had distinct risk factors and predictive models. AKI was a risk factor for both kidney survival and overall survival (OS). Even recovered AKI reduced 10-year kidney survival from 91.7% to 68.4% (p = 0.002) and 10-year OS from 91.1% to 77.7% (p = 0.005).

Case report: unprecedented case of infantile cerebral infarction following COVID-19 and favorable outcome.

The 2019 novel coronavirus, SARS-CoV-2, was highly prevalent in China as of December 2022, causing a range of symptoms, predominantly affecting the respiratory tract. While SARS-CoV-2 infection in children is generally mild, severe cases, especially in infants, are rare. We present a case of a previously healthy 7-month-old infant who developed cerebral infarction and coagulation dysfunction three days after COVID-19 onset. Clinically, the infant had weakness in the left limbs and pinpoint bleeding spots. A cranial magnetic resonance imaging showed ischemic strokes in the right basal ganglia and thalamus. Laboratory tests indicated thrombocytopenia and coagulation dysfunction. Inflammatory cytokines like interleukin-10 were elevated, with increased CD3+, CD4+, and CD8+ T lymphocytes but decreased CD3- CD16+ CD56+ natural killer cells. Treatment included mannitol, dexamethasone, oral aspirin, and vitamins B1 and B6 for reducing intracranial pressure, antiinflammation, anticoagulation, and nerve support, respectively. During the recovery phase, rehabilitation therapy focused on strength training, fine motor skills, and massage therapy. The infant gradually improved and successfully recovered. While rare, such cases can lead to severe complications. These combined efforts were instrumental in achieving significant functional recovery in the patient, demonstrating that even in severe instances of pediatric cerebral infarction due to COVID-19, positive outcomes are attainable with early and comprehensive medical response.

Leisure Activity, Childhood Starvation, and Risk of Incident Diabetes in Older Adults: Evidence From a Chinese Nationwide Cohort Study.

OBJECTIVE: This study explores the impact of leisure activity and the association between childhood starvation and the risk of diabetes in older Chinese adults. DESIGN: Prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study (CLHLS), a nationwide cohort study in China. SETTING AND PARTICIPANTS: A total of 4637 older adults aged ≥65 years, all with documented diabetes history, experiences of childhood starvation, and participation in leisure activities were recruited. METHODS: Childhood starvation exposure was assessed via self-reported responses from a structured questionnaire. The leisure activities were measured by 9 distinctive components and categorized into 3 distinct categories: productive activity, recreational activity, and sedentary activity. Diabetes status was determined by self-reported, physician-diagnosed cases during the follow-up period. Nonparametric survival models were employed for analysis. RESULTS: Over an average follow-up period of 4.3 years, 215 of 4637 participants (4.6%) reported a confirmed diagnosis of diabetes. Nonparametric survival models showed that those reporting childhood starvation had a higher risk of late-life diabetes [hazard ratio (HR) 1.72, 95% CI 1.21-2.44]. Engaging in productive activity (HR 0.90, 95% CI 0.83-0.99) and recreational activity (HR 0.88, 95% CI 0.77-1.00) was linked with a reduced risk of late-life diabetes. Sedentary activity did not show a significant effect. Further analysis highlighted the interactions effects of leisure activities on diabetes risk across different demographic and historical exposure subgroups. CONCLUSIONS AND IMPLICATIONS: Engaging in productive and recreational leisure activities was inversely associated with the risk of diabetes in older adults who experienced childhood starvation. Promoting such activities could be beneficial in mitigating long-term diabetes risk related to early-life nutritional deficiencies.

Recent Advances of Food Hazard Detection Based on Artificial Nanochannel Sensors.

Food quality and safety are related to the health and safety of people, and food hazards are important influencing factors affecting food safety. It is strongly necessary to develop food safety rapid detection technology to ensure food safety. As a new detection technology, artificial nanochannel-based electrochemical and other methods have the advantages of being real-time, simple, and sensitive and are widely used in the detection of food hazards. In this paper, we review artificial nanochannel sensors as a new detection technology in food safety for different types of food hazards: biological hazards (bacteria, toxins, viruses) and chemical hazards (heavy metals, organic pollutants, food additives). At the same time, we critically discuss the advantages and disadvantages of artificial nanochannel sensor detection, as well as the restrictions and solutions of detection, and finally look forward to the challenges and development prospects of food safety detection technology based on the limitations of artificial nanochannel detection. We expect to provide a theoretical basis and inspiration for the development of rapid real-time detection technology for food hazards and the production of portable detection equipment in the future.

Recent Advances in Stimulus-Responsive Nanocarriers for Pesticide Delivery.

In an effort to make pesticide use safer, more efficient, and sustainable, micro-/nanocarriers are increasingly being utilized in agriculture to deliver pesticide-active agents, thereby reducing quantities and improving effectiveness. In the use of nanopesticides, the choice to further design and prepare pesticide stimulus-responsive nanocarriers based on changes in the plant growth environment (light, temperature, pH, enzymes, etc.) has received more and more attention from researchers. Based on this, this paper examines recent advancements in nanomaterials for the design of stimulus-responsive micro-/nanocarriers. It delves into the intricacies of preparation methods, material enhancements, in vivo/ex vivo controlled release, and application techniques for controlled release formulations. The aim is to provide a crucial reference for harnessing nanotechnology to pursue reduced pesticide use and increased efficiency.