The role of sulfur cycle in new particle formation: Cycloaddition reaction of SO3 to H2S.

The chemistry of sulfur cycle contributes significantly to the atmospheric nucleation process, which is the first step of new particle formation (NPF). In the present study, cycloaddition reaction mechanism of sulfur trioxide (SO3) to hydrogen sulfide (H2S) which is a typical air pollutant and toxic gas detrimental to the environment were comprehensively investigate through theoretical calculations and Atmospheric Cluster Dynamic Code simulations. Gas-phase stability and nucleation potential of the product thiosulfuric acid (H2S2O3, TSA) were further analyzed to evaluate its atmospheric impact. Without any catalysts, the H2S + SO3 reaction is infeasible with a barrier of 24.2 kcal/mol. Atmospheric nucleation precursors formic acid (FA), sulfuric acid (SA), and water (H2O) could effectively lower the reaction barriers as catalysts, even to a barrierless reaction with the efficiency of cis-SA > trans-FA > trans-SA > H2O. Subsequently, the gas-phase stability of TSA was investigated. A hydrolysis reaction barrier of up to 61.4 kcal/mol alone with an endothermic isomerization reaction barrier of 5.1 kcal/mol under the catalytic effect of SA demonstrates the sufficient stability of TSA. Furthermore, topological and kinetic analysis were conducted to determine the nucleation potential of TSA. Atmospheric clusters formed by TSA and atmospheric nucleation precursors (SA, ammonia NH3, and dimethylamine DMA) were thermodynamically stable. Moreover, the gradually decreasing evaporation coefficients for TSA-base clusters, particularly for TSA-DMA, suggests that TSA may participate in NPF where the concentration of base molecules are relatively higher. The present new reaction mechanism may contributes to a better understanding of atmospheric sulfur cycle and NPF.

Identify truly high-risk TP53-mutated diffuse large B cell lymphoma patients and explore the underlying biological mechanisms.

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.

MiR-183-5p inhibits lung squamous cell carcinoma survival through disrupting hypoxia adaptation mediated by HIF-1α/NDUFA4L2 axis.

Hypoxia is a common feature of lung squamous cell carcinoma (LUSC), and hypoxia-inducible factor-1 (HIF-1) overexpression is associated with poor clinical outcome in LUSC. NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) is a recently identified target of HIF-1, but its roles in LUSC remain unclear. Herein, the expression and regulatory mechanisms of NDUFA4L2 were investigated in LUSC, and the influences on LUSC cell oxidative metabolism and survival of NDUFA4L2 were determined. The potential microRNA targeting to NDUFA4L2 was identified and its roles on LUSC cell were detected. We found that NDUFA4L2 were overexpressed in LUSC tissues, and that NDUFA4L2 expression correlated with shorter overall survival. NDUFA4L2 was regulated by HIF-1α under hypoxia, and NDUFA4L2 decreased mitochondrial reactive oxygen species (mitoROS) production through inhibiting mitochondrial complex I activity in LUSC cells. NDUFA4L2 silencing effectively suppressed LUSC cell growth and enhanced apoptosis by inducing mitoROS accumulation. Additionally, NDUFA4L2 was a target for miR-183-5p, and LUSC patients with high miR-183-5p levels had better prognoses. MiR-183-5p significantly induced mitoROS production and suppressed LUSC survival through negatively regulating NDUFA4L2 in vitro and in vivo. Our results suggested that regulation of NDUFA4L2 by HIF-1α is an important mechanism promoting LUSC progression under hypoxia. NDUFA4L2 inhibition using enforced miR-183-5p expression might be an effective strategy for LUSC treatment.

Adverse events associated with teriparatide: a real-world disproportionality analysis of the FDA adverse event reporting system (FAERS).

BACKGROUND: Teriparatide is widely used for osteoporosis treatment in various patients, but its safety profile is not fully documented. This study analyzes the FDA pharmacovigilance database to assess teriparatide's safety. RESEARCH DESIGN AND METHODS: Data from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2023 were extracted and analyzed for disproportionality between teriparatide and adverse effects (AE). RESULTS: A total of 66,991 AE reports identified teriparatide as the principal suspect medication, aggregating to 222,116 individual AEs. Notably, healthcare professionals authored 16.1% of these reports (n = 10,809), whereas consumers accounted for the majority with 81.3% (n = 54,474). Teriparatide revealed a marked association with an increased propensity for musculoskeletal and connective tissue disorders (ROR,3.95; 95% CI, 3.91-3.99) at the System Organ Class (SOC) level. Concurrently, 199 preferred terms (PTs) displayed significant disproportionality across all four employed algorithms. CONCLUSIONS: Our study confirms several well-known adverse drug reactions and identifies potential safety issues associated with teriparatide treatment. This contributes to a deeper understanding of the complex relationship between adverse reactions and teriparatide. These findings emphasize the importance of continuous monitoring and ongoing surveillance to promptly identify and effectively manage adverse reactions, thereby enhancing overall patient safety and well-being.

Ribbon-Ordered Superlattice Enables Reversible Anion Redox and Stable High-Voltage Na-Ion Battery Cathodes.

High-voltage layered oxide cathodes attract great attention for sodium-ion batteries (SIBs) due to the potential high energy density, but high voltage usually leads to rapid capacity decay. Herein, a stable high-voltage NaLi0.1Ni0.35Mn0.3Ti0.25O2 cathode with a ribbon-ordered superlattice is reported, and the intrinsic coupling mechanism between structure evolution and the anion redox reaction (ARR) is revealed. Li introduction constructs a special Li-O-Na configuration activating reversible nonbonded O 2p (|O2p)-type ARR and regulates the structure evolution way, enabling the reversible Li ions out-of-layer migration instead of the irreversible transition metal ions out-of-layer migration. The reversible structure evolution enhances the reversibility of the bonded O 2p (O2p)-type ARR and inhibits the generation of oxygen dimers, thus suppressing the irreversible molecular oxygen (O2)-type ARR. After the structure regulation, the structure evolution becomes reversible, |O2p-type ARR is activated, O2p-type ARR becomes stable, and O2-type ARR is inhibited, which largely suppresses the capacity degradation and voltage decay. The discharge capacity is increased from 154 to 168 mA h g-1, the capacity retention after 200 cycles significantly increases from 35 to 84%, and the voltage retention increases from 78 to 93%. This study presents some guidance for the design of high-voltage, O3-type oxide cathodes for high-performance SIBs.

[Spatiotemporal Distribution Characteristics of Ground-level-ozone and Its Relationship with Meteorological Conditions in a Representative City in the Bohai Rim from 2017 to 2022].

In recent years, ground-level-ozone（O3） pollution in urban areas in the Bohai Rim has attracted wide attention. Based on the analysis of the spatiotemporal distribution characteristics of O3 concentration in Dongying, a representative city in the Bohai Rim from 2017 to 2022, the effects of meteorological factors and sea-land breeze circulation on O3 concentration were evaluated. The results showed that： ① From 2017 to 2022, the annual assessment value of O3 concentration in Dongying showed a fluctuating upward trend, and the pollution days with O3 as the primary pollutant increased. O3 pollution mainly occurred in spring, summer, and autumn, with the most severe O3 pollution episodes typically occurring in May and June, and the duration of O3 pollution season tended to be longer. The monthly variation in the daily maximum 8-h average ozone （MDA8 O3） presented a bimodal distribution, with significant increases in the 5th and 25th percentiles, and the spatial distribution was "high in the north and south, low in the middle." In addition, the nocturnal O3 concentration in recent years in Dongying also showed a significant increase trend. ② Meteorological factors greatly influenced O3 concentration in Dongying. When the temperature was greater than 30℃, the relative humidity was less than 50%, and the wind direction was south-southwest or east-northeast, a high O3 value was more likely to occur. Meteorological factors contributed 30% of the MDA8 O3 variation in Dongying during the study period. In the case of moderate and severe O3 pollution, the contribution of meteorological factors to the change in MDA8 O3 could be as high as 40%. ③ To some extent, sea-land breeze contributed to the occurrence of MDA8 O3 exceeding the secondary standard limit value of the National Ambient Air Quality Standard. In the afternoon, the hourly concentration of O3 during the sea-land breeze days was approximately 20 µg·m-3 higher than that during the non-sea-land breeze days. On the days of moderate and severe O3 pollution, the O3 concentration during the sea-land breeze days from 10：00 to 16：00 was higher than that during non-sea-land breeze days, and the O3 concentration was also at a high level from 20：00 to 23：00 on sea-land breeze days. In the O3 pollution season, the sea-land breeze could significantly affect the O3 level in coastal cities, which could bring significant challenges for O3 pollution prevention and control in this region. In the future, cities in the Bohai Rim need to further strengthen regional joint prevention and control of O3 pollution and increase emission reduction efforts of nitrogen oxides and volatile organic compounds. This strategy could effectively lower pollutant concentrations within the land breeze air mass, consequently reducing the impact of the sea breeze air mass on air quality in cities in the Bohai Rim.

Genomic anatomy of homozygous XX females and YY males reveals early evolutionary trajectory of sex-determining gene and sex chromosomes in Silurus fishes.

Sex chromosomes display remarkable diversity and variability among vertebrates. Compared with research on the X/Y and Z/W chromosomes, which have long evolutionary histories in mammals and birds, studies on the sex chromosomes at early evolutionary stages are limited. Here, we precisely assembled the genomes of homozygous XX female and YY male Lanzhou catfish (Silurus lanzhouensis) derived from an artificial gynogenetic family and a self-fertilized family, respectively. Chromosome 24 (Chr24) was identified as the sex chromosome based on resequencing data. Comparative analysis of the X and Y chromosomes showed an approximate 320 kb Y-specific region with a Y-specific duplicate of anti-Mullerian hormone type-II receptor (amhr2y), which is consistent with findings in two other Silurus species but on different chromosomes (Chr24 of S. meridionalis and Chr5 of S. asotus). Deficiency of amhr2y resulted in male-to-female sex reversal, indicating that amhr2y plays a male-determining role in S. lanzhouensis. Phylogenetic analysis and comparative genomics revealed that the common sex-determining gene amhr2y was initially translocated to Chr24 of the Silurus ancestor along with the expansion of transposable elements. Chr24 was maintained as the sex chromosome in S. meridionalis and S. lanzhouensis, whereas a sex-determining region transition triggered sex chromosome turnover from Chr24 to Chr5 in S. asotus. Additionally, gene duplication, translocation, and degeneration were observed in the Y-specific regions of Silurus species. These findings present a clear case for the early evolutionary trajectory of sex chromosomes, including sex-determining gene origin, repeat sequence expansion, gene gathering and degeneration in sex-determining region, and sex chromosome turnover.

Hibernating/Awakening Nanomotors Promote Highly Efficient Cryopreservation by Limiting Ice Crystals.

The disruptions caused by ice crystal formation during the cryopreservation of cells and tissues can cause cell and tissue damage. Thus, preventing such damage during cryopreservation is an important but challenging goal. Here, a hibernating/awakening nanomotor with magnesium/palladium covering one side of a silica platform (Mg@Pd@SiO2) is proposed. This nanomotor is used in the cultivation of live NCM460 cells to demonstrate a new method to actively limit ice crystal formation and enable highly efficient cryopreservation. Cooling Mg@Pd@SiO2 in solution releases Mg2+/H2 and promotes the adsorption of H2 at multiple Pd binding sites on the cell surface to inhibit ice crystal formation and cell/tissue damage; additionally, the Pd adsorbs and stores H2 to form a hibernating nanomotor. During laser-mediated heating, the hibernating nanomotor is activated (awakened) and releases H2, which further suppresses recrystallization and decreases cell/tissue damage. These hibernating/awakening nanomotors have great potential for promoting highly efficient cryopreservation by inhibiting ice crystal formation.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) as a predictor of all-cause and cardiovascular mortality in US adults with diabetes or prediabetes: NHANES 1999-2018.

BACKGROUND: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes. METHODS: This study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999-2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality. RESULTS: During a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68-0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57-0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06-1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00-1.16). CONCLUSIONS: Among US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.

Unlocking the Reverse Targeting Mechanisms of Cannabidiol: Unveiling New Therapeutic Avenues.

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the main components of Cannabis sativa plants, have attracted a significant amount of attention due to their biological activities. This study identified GPR18 as the target of partial agonist CBD activating the p42/p44 MAPK pathway leading to migration of endometrial epithelial cells. Induced fit docking (IFD) showed that the affinity of THC for GPR18 is higher than that of CBD, and molecular dynamics (MD) simulations showed that CBD-GPR18 complexes at 130/200 ns might have stable conformations, potentially activating GPR18 by changing the distances of key residues in its active pocket. In contrast, THC maintains "metastable" conformations, generating a "shrinking space" leading to full agonism of THC by adding mechanical constraints in GPR18's active pocket. Steered molecular dynamics (SMD) revealed GPR18's active pocket was influenced more by CBD's partial agonism compared with THC. This combined IFD-MD-SMD method may be used to explain the mechanism of activation of partial or full agonists of GPR18.

Controlled Defective Engineering on CuIr Catalyst Promotes Nitrate Selective Reduction to Ammonia.

Electrochemical nitrate reduction reaction (NO3-RR) is a promising low-carbon and environmentally friendly approach for the production of ammonia (NH3). Herein, we develop a high-temperature quenched copper (Cu) catalyst with the aim of inducing nonequilibrium phase transformation, revealing the multiple defects (distortion, dislocations, vacancies, etc.) presented in Cu, which lead to low overpotential for NO3-RR and high efficiency for NH3 production. Further loading a low content of iridium (Ir) species on the Cu surface improves the reactivity and ammonia selectivity. The resultant CuIr electrode exhibits a Faradaic efficiency of 93% and a record yield of 6.01 mmol h-1 cm-2 at -0.22 VRHE exceeding those of state-of-the-art NO3-RR catalysts. Detailed investigations have demonstrated that the synergistic effect between multiple defects and Ir decoration effectively regulate the d-band center of copper, change the adsorption state of the catalyst surface, and promote the adsorption and reduction of intermediates and reactants. The strong H* adsorption ability of the Ir element provides more active hydrogen for the generation of ammonia, promoting the reduction of nitrate to NH3.

ALKBH5-Mediated m6A Modification Drives Apoptosis in Renal Tubular Epithelial Cells by Negatively Regulating MUC1.

Dysregulation of renal tubular epithelial cell (RTEC) apoptosis is one of the critical steps underlying the occurrence and development of nephrolithiasis. Although N6-methyladenosine (m6A) modification has been extensively studied and associated with various pathologic processes, research on its specific role in RTEC injury and apoptosis remains limited. In this study, we found that overexpression of ALKBH5 reduced the level of m6A modification in RTEC cells and notably promoted RTEC apoptosis. Further mechanism studies revealed that ALKBH5 mainly  decreased the m6A level on the mRNA of  Mucin 1 (MUC1) gene in RTECs. Moreover, ALKBH5  impaired the stability of MUC1 mRNA in RTECs, leading to  attenuated expression of MUC1. Finally, we determined that the ALKBH5-MUC1 axis primarily facilitated RTEC apoptosis by regulating the PI3K/Akt signaling pathway. This study revealed the critical role of the ALKBH5-MUC1-PI3K/Akt regulatory system in RTEC apoptosis and provided new therapeutic targets for treating nephrolithiasis.

Theory-driven design of cadmium mineralizing layered double hydroxides for environmental remediation.

The environmental concern posed by toxic heavy metal pollution in soil and water has grown. Ca-based layered double hydroxides (LDHs) have shown exceptional efficacy in eliminating heavy metal cations through the formation of super-stable mineralization structures (SSMS). Nevertheless, it is still unclear how the intricate coordination environment of Ca2+ in Ca-based LDH materials affects the mineralization performance, which hinders the development and application of Ca-based LDH materials as efficient mineralizers. Herein, we discover that, in comparison to a standard LDH, the mineralization efficiency for Cd2+ ions may be significantly enhanced in the pentacoordinated structure of defect-containing Ca-5-LDH utilizing both density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Furthermore, the calcination-reconstruction technique can be utilized to successfully produce pentacoordinated Ca-5-LDH. Subsequent investigations verified that Ca-5-LDH exhibited double the mineralization performance (421.5 mg g-1) in comparison to the corresponding pristine seven coordinated Ca-7OH/H2O-LDH (191.2 mg g-1). The coordination-relative mineralization mechanism of Ca-based LDH was confirmed by both theoretical calculations and experimental results. The understanding of LDH materials and their possible use in environmental remediation are advanced by this research.

Claudin18.2-Targeted SPECT/CT Imaging for Gastric Cancer: Preclinical Evaluation and Clinical Translation of the 99mTc-Labeled Nanobody (PHG102) Radiotracer.

Claudin18.2 (CLDN18.2) has emerged as a significant target in the treatment of advanced gastric cancer. The screening of patients positive for CLDN18.2 is crucial for the effective application of targeted therapies specific to CLND18.2. In this study, we developed a novel nanobody-based probe, [99mTc]Tc-PHG102, for use in nuclear medicine. We analyzed its radiochemical yield and stability to ensure accurate probe characterization. Additionally, we assessed the probe's affinity and specificity toward the CLDN18.2 target and evaluated its efficacy in the BGC82318.2 xenograft model for SPECT/CT imaging of gastric cancer. The binding of [99mTc]Tc-PHG102 to HEK-293T18.2 and BGC82318.2 cells was notably higher than its binding to HEK-293T18.1, HEK-293T, and BGC823 cells, with bound values of 12.87 ± 1.46%, 6.16 ± 0.34%, 1.25 ± 0.22%, 1.14 ± 0.26%, and 1.32 ± 0.07% AD, respectively. The binding ability of [99mTc]Tc-PHG102 was significantly different between CLDN18.2-positive and negative cells (P < 0.001). Imaging results demonstrated a time-dependent tumor accumulation of the radiotracer. Notably, at 0.5 h postinjection, rapid accumulation was observed with an average tumor uptake of 4.63 ± 0.81% ID/cc (n = 3), resulting in clear tumor visualization. By 1 h postinjection, as [99mTc]Tc-PHG102 was rapidly metabolized, a decrease in uptake by other organs was noted. Preliminary clinical imaging trials further confirmed the safety and effectiveness of the probe, indicating specificity for lesions expressing CLDN18.2 in gastric cancer and favorable in vivo metabolic properties. In conclusion, the nanobody-based probe [99mTc]Tc-PHG102 proves to be a safe and effective tool for detecting CLDN18.2 expression levels in gastric cancer tumors and for screening CLDN18.2-positive patients.

Single-atom Zr-doped CoOOH with enhanced electrical conductivity as a signal amplifier and detection probe for the indirect non-enzymatic electrochemical determination of malathion in foods.

Herein, a novel electrochemical sensor based on zirconium-doped cobalt oxyhydroxide (ZrCoOOH) was proposed for highly sensitive non-enzymatic determination of malathion (MAL). The doping of Zr can improve the electrical conductivity of CoOOH, of which the transfer resistance was reduced from 241.1 Ω to 140.2 Ω. Furthermore, the X-ray photoelectron spectroscopy confirmed that part of Co2+ was converted to Co3+ due to the introduction of Zr. The Co3+ in ZrCoOOH could react with MAL to form Co2+, which enhanced the electrooxidation current of Co2+. Therefore, the peak current of Co2+ was served as detection probe for MAL. Under optimal conditions, the developed sensor established the linear relationship for MAL in the concentration range of 0.001-10.0 µM with a low limit of detection (0.64 nM). The constructed sensor was employed to detect MAL in food samples (peach, kiwi fruit, spinach and tomato), verifying the accuracy and practicability of the sensor.

Development of ZrO(OH)2@HCS co-modified molecularly imprinted gel-based electrochemical sensing platform for sensitive and selective detection of tert-butylhydroquinone in foods.

Herein, a novel molecularly imprinted gel (MIG)-based electrochemical sensor equipped with hydrated zirconium oxide@hollow carbon spheres (ZrO(OH)2@HCS) was developed for highly sensitive and selective detection of tert-butylhydroquinone (TBHQ) in foods. The MIG was synthesized by using L-histidine to rapidly cross-link cationic guar gum, acrylamide and TBHQ through intermolecular hydrogen bonds and electrostatic interactions at room temperature, which offered outstanding specific recognition performance for TBHQ. ZrO(OH)2@HCS possessing excellent conductivity and water dispersibility was employed for signal amplification. Under optimal conditions, the MIG-ZrO(OH)2@HCS/GCE sensor showed a wide dynamic detection range (0.025-100 µM) with a low limit of detection (6.7 nM). TBHQ recovery experiments were conducted in spiked peanut oil and milk powder, yielding excellent recoveries. Moreover, the sensor was successfully utilized to detect TBHQ levels in snowflake chicken cutlets, crispy fried pork and boneless chicken fillets, and the results were in agreement with those obtained by the high performance liquid chromatography method.

Myelin debris phagocytosis in demyelinating disease.

Demyelinating diseases are often caused by a variety of triggers, including immune responses, viral infections, malnutrition, hypoxia, or genetic factors, all of which result in the loss of myelin in the nervous system. The accumulation of myelin debris at the lesion site leads to neuroinflammation and inhibits remyelination; therefore, it is crucial to promptly remove the myelin debris. Initially, Fc and complement receptors on cellular surfaces were the primary clearance receptors responsible for removing myelin debris. However, subsequent studies have unveiled the involvement of additional receptors, including Mac-2, TAM receptors, and the low-density lipoprotein receptor-related protein 1, in facilitating the removal process. In addition to microglia and macrophages, which serve as the primary effector cells in the disease phase, a variety of other cell types such as astrocytes, Schwann cells, and vascular endothelial cells have been demonstrated to engage in the phagocytosis of myelin debris. Furthermore, we have concluded that oligodendrocyte precursor cells, as myelination precursor cells, also exhibit this phagocytic capability. Moreover, our research group has innovatively identified the low-density lipoprotein receptor as a potential phagocytic receptor for myelin debris. In this article, we discuss the functional processes of various phagocytes in demyelinating diseases. We also highlight the alterations in signaling pathways triggered by phagocytosis, and provide a comprehensive overview of the various phagocytic receptors involved. Such insights are invaluable for pinpointing potential therapeutic strategies for the treatment of demyelinating diseases by targeting phagocytosis.

Atomically Precise Regulation of the N-Heterocyclic Microenvironment in Triazine Covalent Organic Frameworks for Coenzyme Photocatalytic Regeneration.

Artificial photosynthesis represents a sustainable strategy for accessing high-value chemicals; however, the conversion efficiency is significantly limited by its difficulty in the cycle of coenzymes such as NADH. In this study, we report a series of isostructural triazine covalent organic frameworks (COFs) and explore their N-substituted microenvironment-dependent photocatalytic activity for NADH regeneration. We discovered that the rational alteration of N-heterocyclic species, which are linked to the triazine center through an imine linkage, can significantly regulate both the electron band structure and planarity of a COF layer. This results in different separation efficiencies of the photoinduced electron-hole pairs and electron transfer behavior within and between individual layers. The optimal COF catalyst herein achieves an NADH regeneration capacity of 89% within 20 min, outperforming most of the reported nanomaterial photocatalysts. Based on this, an artificial photosynthesis system is constructed for the green synthesis of a high-value compound, L-glutamate, and its conversion efficiency significantly surpasses the enzymatic approach without the NADH photocatalytic cycle. This work offers new insights into the coenzyme regeneration by means of regulating the distal heterocyclic microenvironment of a COF skeleton, holding great potential for the green photosynthesis of important chemicals.

[Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues]. / 产科抗磷脂综合征的诊治原则与热点问题述评.

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein Ⅰ domain Ⅰ antibody (aß2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.

Transcriptome Dynamics and Cell Dialogs Between Oocytes and Granulosa Cells in Mouse Follicle Development.

The development and maturation of follicles is a sophisticated and multistage process. The dynamic gene expression of oocytes and their surrounding somatic cells and the dialogs between these cells are critical to this process. In this study, we accurately classified the oocyte and follicle development into nine stages and profiled the gene expression of mouse oocytes and their surrounding granulosa cells and cumulus cells. The clustering of the transcriptomes showed the trajectories of two distinct development courses of oocytes and their surrounding somatic cells. Gene expression changes precipitously increased at Type 4 stage and drastically dropped afterward within both oocytes and granulosa cells. Moreover, the number of differentially expressed genes between oocytes and granulosa cells dramatically increased at Type 4 stage, most of which persistently passed on to the later stages. Strikingly, cell communications within and between oocytes and granulosa cells became active from Type 4 stage onward. Cell dialogs connected oocytes and granulosa cells in both unidirectional and bidirectional manners. TGFB2/3, TGFBR2/3, INHBA/B, and ACVR1/1B/2B of TGF-ß signaling pathway functioned in the follicle development. NOTCH signaling pathway regulated the development of granulosa cells. Additionally, many maternally DNA methylation- or H3K27me3-imprinted genes remained active in granulosa cells but silent in oocytes during oogenesis. Collectively, Type 4 stage is the key turning point when significant transcription changes diverge the fate of oocytes and granulosa cells, and the cell dialogs become active to assure follicle development. These findings shed new insights on the transcriptome dynamics and cell dialogs facilitating the development and maturation of oocytes and follicles.