DNA polymerase delta governs parental histone transfer to DNA replication lagging strand.

Chromatin replication is intricately intertwined with the recycling of parental histones to the newly duplicated DNA strands for faithful genetic and epigenetic inheritance. The transfer of parental histones occurs through two distinct pathways: leading strand deposition, mediated by the DNA polymerase ε subunits Dpb3/Dpb4, and lagging strand deposition, facilitated by the MCM helicase subunit Mcm2. However, the mechanism of the facilitation of Mcm2 transferring parental histones to the lagging strand while moving along the leading strand remains unclear. Here, we show that the deletion of Pol32, a nonessential subunit of major lagging-strand DNA polymerase δ, results in a predominant transfer of parental histone H3-H4 to the leading strand during replication. Biochemical analyses further demonstrate that Pol32 can bind histone H3-H4 both in vivo and in vitro. The interaction of Pol32 with parental histone H3-H4 is disrupted through the mutation of the histone H3-H4 binding domain within Mcm2. Our findings identify the DNA polymerase δ subunit Pol32 as a critical histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication.

Mechanism of Salvia miltiorrhiza Bunge extract to alleviate Chronic Sleep Deprivation-Induced cognitive dysfunction in rats.

BACKGROUND: Bidirectional communication between the gut microbiota and the brain may play an essential role in the cognitive dysfunction associated with chronic sleep deprivation(CSD). Salvia miltiorrhiza Bunge (Danshen, DS), a famous Chinese medicine and functional tea, is extensively used to protect learning and memory capacities, although the mechanism of action remains unknown. PURPOSE: The purpose of this research was to explore the efficacy and the underlying mechanism of DS in cognitive dysfunction caused by CSD. METHODS: DS chemical composition was analyzed by UPLC-QTOF-MS/MS. Forty rats were randomly assigned to five groups (n = 8): control (CON), model (MOD), low- (1.35 g/kg, DSL), high-dose (2.70 g/kg, DSH) DS group, and Melatonin(100 mg/kg, MT) group. A CSD rat model was established over 21 days. DS's effects and the underlying mechanism were explored using the open-field test(OFT), Morris water-maze(MWM), tissue staining(Hematoxylin and Eosin Staining, Nissl staining, Alcian blue-periodic acid SCHIFF staining, and Immunofluorescence), enzyme-linked immunosorbent assay, Western blot, quantitative real-time polymerase chain reaction(qPCR), and 16S rRNA sequencing. RESULTS: We demonstrated that CSD caused gut dysbiosis and cognitive dysfunction. Furthermore, 16S rRNA sequencing demonstrated that Firmicutes and Proteobacteria were more in fecal samples from model group rats, whereas Bacteroidota and Spirochaetota were less. DS therapy, on the contrary hand, greatly restored the gut microbial community, consequently alleviating cognitive impairment in rats. Further research revealed that DS administration reduced systemic inflammation via lowering intestinal inflammation and barrier disruption. Following that, DS therapy reduced Blood Brain Barrier(BBB) and neuronal damage, further decreasing neuroinflammation in the hippocampus(HP). Mechanistic studies revealed that DS therapy lowered lipopolysaccharide (LPS) levels in the HP, serum, and colon, consequently blocking the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products(IL-1ß, IL-6, TNF-α, iNOS, and COX2) in the HP and colon. CONCLUSION: DS treatment dramatically improved spatial learning and memory impairments in rats with CSD by regulating the composition of the intestinal flora, preserving gut and brain barrier function, and reducing inflammation mediated by the LPS-TLR4 signaling pathway. Our findings provide novel insight into the mechanisms by which DS treats cognitive dysfunction caused by CSD.

Transcriptomic sex differences in postmortem brain samples from patients with psychiatric disorders.

Many psychiatric disorders exhibit sex differences, but the underlying mechanisms remain poorly understood. We analyzed transcriptomics data from 2,160 postmortem adult prefrontal cortex brain samples from the PsychENCODE consortium in a sex-stratified study design. We compared transcriptomics data of postmortem brain samples from patients with schizophrenia (SCZ), bipolar disorder (BD), and autism spectrum disorder (ASD) to transcriptomics data of postmortem control brains from individuals without a known history of psychiatric disease. We found that brain samples from females with SCZ, BD and ASD showed a higher burden of transcriptomic dysfunction than did brain samples from males with these disorders. This observation was supported by the larger number of differentially expressed genes (DEGs) and a greater magnitude of gene expression changes observed in female versus male brain specimens. Additionally, female patient brain samples showed greater overall connectivity dysfunction, defined by a higher proportion of gene co-expression modules with connectivity changes and higher connectivity burden, indicating a greater degree of gene co-expression variability. We identified several gene co-expression modules enriched in sex-biased DEGs and identified genes from a genome-wide association study that were involved in immune and synaptic functions across different brain cell types. We found a number of genes as hubs within these modules including those encoding SCN2A, FGF14, and C3. Our results suggest that in the context of psychiatric diseases, males and females exhibit different degrees of transcriptomic dysfunction, and implicate immune and synaptic-related pathways in these sex differences.

Influence of back optic zone diameter on corneal morphology with orthokeratology lenses.

OBJECTIVE: This study aimed to compare the changes in corneal morphological characteristics in corneal topography assessments performed after wearing orthokeratology (OK) lenses with different back optic zone diameters (BOZDs). These changes included the change ratios of the apical corneal power (ACP), the maximum relative corneal refractive power (mRCRP), and the treatment zone diameter (TZD). METHODS: Data from 133 children with myopia (average age 9.50 ± 1.23 years) treated at Fudan University Eye and Ear, Nose, and Throat Hospital were retrospectively analyzed. All participants wore the same brand of tangent-design OK lens (corneal refractive therapy, CRT). According to the BOZD, the patients were divided into two groups, of 5.0 and 6.0 mm BOZD, respectively. Corneal topography was analyzed at baseline, as well as 1 day, 1 week, and 1 month after wearing the lenses, and the change ratios of ACP, mRCRP, and TZD were compared between the two groups. RESULTS: The change ratio of the ACP did not differ significantly between the BOZD 5.0 and 6.0 groups after 1 day or 1 week of lens wear (P = 0.170 and P = 0.113, respectively). However, after 1 month of lens wear, the change ratio of the ACP in the BOZD 5.0 group was significantly larger than that in the BOZD 6.0 group (P < 0.001). After 1 month of lens wear, the mRCRP along the horizontal and vertical meridians was higher (P < 0.05) and the TZD was significantly smaller (P < 0.001) in the BOZD 5.0 group than in the BOZD 6.0 group. CONCLUSION: In CRT OK lenses, a small BOZD lens can produce faster corneal shaping, a larger mRCRP, and a smaller TZD, which may have a better effect on slowing ocular axial length elongation. The lens parameters are also a factor affecting the TZD.

Chronotoxici-Plate Containing Droplet-Engineered Rhythmic Liver Organoids for Drug Toxicity Evaluation.

The circadian clock coordinates the daily rhythmicity of biological processes, and its dysregulation is associated with various human diseases. Despite the direct targeting of rhythmic genes by many prevalent and World Health Organization (WHO) essential drugs, traditional approaches can't satisfy the need of explore multi-timepoint drug administration strategies across a wide range of drugs. Here, droplet-engineered primary liver organoids (DPLOs) are generated with rhythmic characteristics in 4 days, and developed Chronotoxici-plate as an in vitro high-throughput automated rhythmic tool for chronotherapy assessment within 7 days. Cryptochrome 1 (Cry1) is identified as a rhythmic marker in DPLOs, providing insights for rapid assessment of organoid rhythmicity. Using oxaliplatin as a representative drug, time-dependent variations are demonstrated in toxicity on the Chronotoxici-plate, highlighting the importance of considering time-dependent effects. Additionally, the role of chronobiology is underscored in primary organoid modeling. This study may provide tools for both precision chronotherapy and chronotoxicity in drug development by optimizing administration timing.

Redistribution of Epithelium and Stroma and Their Relationship With Corneal Curvature After 1-Month Cessation of Overnight Orthokeratology.

OBJECTIVES: To investigate the changes in the thickness of epithelium and stroma and their relationship with corneal curvature following the cessation of overnight orthokeratology for a period of 1 month. METHODS: This prospective study consecutively included 20 juveniles (20 right eyes) who had undergone overnight orthokeratology for a minimum of one year and were willing to discontinue the treatment. The study measured and compared epithelial and corneal curvature using optical coherence tomography and Medmont topographer at the first day of cessation and 1 month after cessation. In addition, changes in uncorrected visual acuity and refractive error before and after the cessation of the treatment were analyzed. RESULTS: The study found a significant increase in the thickness of the epithelium in the central 2-mm area after the cessation of the treatment (t = -4.807, P <0.001). Moreover, the stroma in the paracentral area (2-5 mm) and peripheral area (5-6 mm) showed a general thinning trend ( P =0.016, P =0.016). Regarding the correlation analysis, the change in central epithelial thickness (ΔCET) was significantly correlated with the change in paracentral corneal curvature (ΔPCCC) (r=0.610, P =0.007) and the change in peripheral corneal curvature (ΔPCC) (r=0.597, P =0.009). Similarly, the change in central stromal thickness (ΔCST) was significantly correlated with the change in central corneal curvature (ΔCCC) (r=0.500, P =0.035), ΔPCCC (r=0.700, P =0.001), and ΔPCC (r=0.635, P =0.005). CONCLUSIONS: The study found that the corneal remodeling induced by orthokeratology was reversible after the cessation of the treatment. Specifically, changes in the epithelium were found to be more prominent in the central area, while changes in the stroma were more pronounced in the paracentral and peripheral areas. In addition, the study established a significant correlation between central corneal remodeling and changes in curvature.

Low repetition rate 915†nm figure-9 ultrafast laser with all-fiber structure.

The advent of optical metrology applications has necessitated the development of compact, reliable, and cost-effective picosecond lasers operating around 900 nm, specifically catering to the requirements of precise ranging. In response to this demand, our work introduces an innovative solution-an all-fiber, all-polarization-maintaining (PM) figure-9 mode-locked laser operating at 915 nm. The proposed figure-9 Nd-doped fiber laser has a 69.2 m long cavity length, strategically designed and optimized to yield pulses with a combination of high pulse energy and low repetition rate. The laser can generate 915 nm laser pulses with a pulse energy of 4.65 nJ, a pulse duration of 15.2 ps under the repetition rate of 3.05 MHz. The 1064 nm amplified spontaneous emission (ASE) is deliberately filtered out, in order to prevent parasitic lasing and increase the spectral proportion of the 915 nm laser. The all-PM fiber configuration of this laser imparts exceptional mode-locking performance and environmental robustness, which is confirmed by long-term output power and spectral stability test. This compact and long-term reliable fiber laser could be a promising light source for applications like inter-satellite ranging.

Clinical differences between outpatients with and without internet addiction and emotional disorders: a prospective naturalistic outcome study.

Background/Objective: as internet use becomes increasingly ingrained in contemporary society, internet addiction (IA) has emerged as a global public health concern. There is ongoing debate regarding whether IA represents a distinct psychological disorder or a secondary manifestation of other existing disorders. This study aimed to examine the pathological relationship between IA and emotional disorders (ED). Method: this study compared pre-treatment characteristics and treatment process of three groups of patients (N=1292) in a naturalistic treatment setting: IA only, ED only, and comorbidity of IA and ED. Results: the IA only group differed from the other groups by reporting the highest levels of life satisfaction, adaptive emotion regulation, as well as risk behavior urges at intake. In addition, the IA only group displayed the lowest level of depressive and anxiety symptoms throughout the treatment. Conclusion: our findings contribute to a better understanding of the discreteness of IA as a potential psychological disorder and inform more effective treatment strategies for IA and its comorbid conditions.

Propofol and salvianolic acid A synergistically attenuated cardiac ischemia-reperfusion injury in diabetic mice via modulating the CD36/AMPK pathway.

Background: Prevention of diabetic heart myocardial ischemia-reperfusion (IR) injury (MIRI) is challenging. Propofol attenuates MIRI through its reactive oxygen species scavenging property at high doses, while its use at high doses causes hemodynamic instability. Salvianolic acid A (SAA) is a potent antioxidant that confers protection against MIRI. Both propofol and SAA affect metabolic profiles through regulating Adenosine 5'-monophosphate-activated protein kinase (AMPK). The aim of this study was to investigate the protective effects and underlying mechanisms of low doses of propofol combined with SAA against diabetic MIRI. Methods: Diabetes was induced in mice by a high-fat diet followed by streptozotocin injection, and MIRI was induced by coronary artery occlusion and reperfusion. Mice were treated with propofol at 46 mg/kg/h without or with SAA at 10 mg/kg/h during IR. Cardiac origin H9c2 cells were exposed to high glucose (HG) and palmitic acid (PAL) for 24 h in the absence or presence of cluster of differentiation 36 (CD36) overexpression or AMPK gene knockdown, followed by hypoxia/reoxygenation (HR) for 6 and 12 h. Results: Diabetes-exacerbated MIRI is evidenced as significant increases in post-ischemic infarction with reductions in phosphorylated (p)-AMPK and increases in CD36 and ferroptosis. Propofol moderately yet significantly attenuated all the abovementioned changes, while propofol plus SAA conferred superior protection against MIRI to that of propofol. In vitro, exposure of H9c2 cells under HG and PAL decreased cell viability and increased oxidative stress that was concomitant with increased levels of ferroptosis and a significant increase in CD36, while p-AMPK was significantly reduced. Co-administration of low concentrations of propofol and SAA at 12.5 µM in H9c2 cells significantly reduced oxidative stress, ferroptosis and CD36 expression, while increasing p-AMPK compared to the effects of propofol at 25 µM. Moreover, either CD36 overexpression or AMPK silence significantly exacerbated HR-induced cellular injuries and ferroptosis, and canceled propofol- and SAA-mediated protection. Notably, p-AMPK expression was downregulated after CD36 overexpression, while AMPK knockdown did not affect CD36 expression. Conclusions: Combinational usage of propofol and SAA confers superior cellular protective effects to the use of high-dose propofol alone, and it does so through inhibiting HR-induced CD36 overexpression to upregulate p-AMPK.

One-dimensional Ga2O3-Al2O3 nanofibers with unsaturated coordination Ga: Catalytic dehydrogenation of propane under CO2 atmosphere with excellent stability.

The pressing demand for propylene has spurred intensive research on the catalytic dehydrogenation of propane to produce propylene. Gallium-based catalysts are regarded as highly promising due to their exceptional dehydrogenation activity in the presence of CO2. However, the inherent coking issue associated with high temperature reactions poses a constraint on the stability development of this process. In this study, we employed the electrospinning method to prepare a range of Ga2O3-Al2O3 mixed oxide one-dimensional nanofiber catalysts with varying molar ratios for CO2 oxidative dehydrogenation of propane (CO2-OPDH). The propane conversion was up to 48.4 % and the propylene selectivity was high as 96.8 % at 500 °C, the ratio of propane to carbon dioxide is 1:2. After 100 h of reaction, the catalyst still maintains approximately 10 % conversion and exhibits a propylene selectivity of around 98 %. The electrospinning method produces one-dimensional nanostructures with a larger specific surface area, unique multi-stage pore structure and low-coordinated Ga3+, which enhances mass transfer and accelerates reaction intermediates. This results in less coking and improved catalyst stability. The high activity of the catalyst is attributed to an abundance of low-coordinated Ga3+ ions associated with weak/medium-strong Lewis acid centers. In situ infrared analysis reveals that the reaction mechanism involves a two-step dehydrogenation via propane isocleavage, with the second dehydrogenation of Ga-OR at the metal-oxygen bond being the decisive speed step.

Ferroptosis is involved in trophoblast cells cytotoxicity induced by black phosphorus nanoparticles.

Black phosphorus (BP) is a new type of nanomaterial, which has been widely used in many biomedical fields due to its superior properties, but there are few studies on the toxicity of BP, especially in the reproductive system. To explore the effects of BP exposure on reproduction and reveal its molecular mechanism, we firstly investigated the potential toxicity of black phosphorus nanoparticles (BPNPs) in vivo. The results showed that BP exposure in pregnant mice can reduce the weight of fetal mice and placenta. H&E staining further indicated the changes of placental cross-section and vascular remodeling after BP treatment. Then, human exvillous trophoblast HTR8/SVneo was treated with different concentrations of BPNPs. We found that BPNPs induced significant cytotoxicity, including dose-dependent reduction of cell viability and proliferation. Trophoblast cell migration and invasion were also impaired by BPNPs exposure. Moreover, pretreatment with Cytochalasin D (Cyto-D), a classical phagocytic inhibitor, alleviated the decline of cell viability induced by BPNPs. Transcriptome sequencing showed that BPNPs exposure led to ferroptosis. Subsequently, the related indexes of ferroptosis were detected, including increase of iron ion concentration, decrease of the ferroptosis marker, GPX4 (Glutathione Peroxidase 4), increase of FTL (Ferritin Light Chain), and increase of lipid peroxidation indexes (MDA level and decrease of GSH level). In addition, ferroptosis inhibitors (Fer-1 and DFO) pretreatment can alleviate both the cytotoxic effects and functional impairment induced by BPNPs. In summary, our study confirmed the reproductive toxicity of BPNPs for the first time, and constructed BPNPs injury model in vitro using human villus trophoblast cells and revealed the role of ferroptosis in this process, which deepened our understanding of the biosafety of black phosphorus nanomaterials.

Discovery of novel HER2 targeting peptide-camptothecin conjugates with effective suppression for selective cancer treatment.

Due to the strong selectivity and permeability of tumor tissue, anti-cancer peptide-drug conjugates (PDCs) can accumulate high concentration of toxic payloads at the target, effectively killing tumor cells. This approach holds great promise for tumor-targeted treatment. In our previous study, we identified the optimal peptide P1 (NPNWGRSWYNQRFK) targeting HER2 from pertuzumab, a monoclonal antibody that blocks the HER2 signaling pathway. Here, a series of PDCs were constructed through connecting P1 and CPT with different linkers. Among these, Z8 emerged as the optimal compound, demonstrating good antitumor activity and targeting ability in biological activity tests. Z8 exhibited IC50 values of 1.04 ± 0.24 µM and 1.91 ± 0.71 µM against HER2-positive SK-BR-3 and NCI-N87 cells, respectively. Moreover, superior antitumor activity and higher biosafety of Z8 were observed compared to the positive control CPT in vivo, suggesting a novel idea for the construction of PDCs.

N-acetylcysteine Protects Against Myocardial Ischemia-Reperfusion Injury Through Anti-ferroptosis in Type 1 Diabetic Mice.

The hearts of subjects with diabetes are vulnerable to ischemia-reperfusion injury (IRI). In contrast, experimentally rodent hearts have been shown to be more resistant to IRI at the very early stages of diabetes induction than the heart of the non-diabetic control mice, and the mechanism is largely unclear. Ferroptosis has recently been shown to play an important role in myocardial IRI including that in diabetes, while the specific mechanisms are still unclear. Non-diabetic control (NC) and streptozotocin-induced diabetic (DM) mice were treated with the antioxidant N-acetylcysteine (NAC) in drinking water for 4 week starting at 1 week after diabetes induction. Mice were subjected to myocardial IRI induced by occluding the coronary artery for 30 min followed by 2 h of reperfusion, subsequently at 1, 2, and 5 week of diabetes induction. The post-ischemic myocardial infarct size in the DM mice was smaller than that in NC mice at 1 week of diabetes but greater than that in the NC mice at 2 and 5 week of diabetes, which were associated with a significant increase of ferroptosis at 2 and 5 week but a significant reduction of ferroptosis at 1 week of diabetes. NAC significantly attenuated post-ischemic ferroptosis as well as oxidative stress and reduced infarct size at 2 and 5 week of diabetes. Application of erastin, a ferroptosis inducer, reversed the cardioprotective effects of NAC. It is concluded that increased oxidative stress and ferroptosis are the major factors attributable to the increased vulnerability to myocardial IRI in diabetes and that attenuation of ferroptosis represents a major mechanism whereby NAC confers cardioprotection against myocardial IRI in diabetes.

In Situ Synthesis of Self-Assembly Supramolecular Crystal Seeds within Continuous Carbon Nanofibers for Improved Fiber Graphitic Structure.

The utilization of carbon-based fibers as a fundamental constituent holds strong appeal for diverse materials and devices. However, the poor fiber graphitic structure resulting from the heat treatment of atactic polyacrylonitrile (PAN) precursors often leads to a modest performance of carbon-based fibers. This paper takes electrospun carbon nanofibers (CNFs) as the research object and provides a seed-assisted graphitization strategy to improve the fiber graphitic structures. The typical melamine/cyanuric acid self-assembly precursor of graphitic carbon nitride is applied as supramolecular seeds in CNFs and demonstrates significant promotion of fiber graphitization, while it decomposes at elevated temperatures. Further studies show that the higher carbon content contributes to the better heat resistance of seeds; thus, nanoscale 2,6-diaminopyridine/cyanuric acid and 2,4,6-triaminopyrimidine/barbituric acid supramolecular seeds are developed. Both systems can be uniformly distributed in PAN precursors through in situ self-assembly and withstand high-temperature carbonization without severe pyrolysis. The dispersed seeds contribute to the formation of fibrillar PAN crystals and promote their conversion to ordered graphitic domains through nucleation and templating roles. The obtained CNFs exhibit increased crystallinity and graphitization degree with improved orientation and refined size of fiber crystals. As a result, the strength, modulus, and elongation at break of CNFs are comprehensively enhanced.

Association between Clinical Characteristics and Microbiota in Bronchiectasis Patients Based on Metagenomic Next-Generation Sequencing Technology.

This study aimed to investigate the disparities between metagenomic next-generation sequencing (mNGS) and conventional culture results in patients with bronchiectasis. Additionally, we sought to investigate the correlation between the clinical characteristics of patients and their microbiome profiles. The overarching goal was to enhance the effective management and treatment of bronchiectasis patients, providing a theoretical foundation for healthcare professionals. A retrospective survey was conducted on 67 bronchiectasis patients admitted to The First Hospital of Jiaxing from October 2019 to March 2023. Clinical baseline information, inflammatory indicators, and pathogen detection reports, including mNGS, conventional blood culture, bronchoalveolar lavage fluid (BALF) culture, and sputum culture results, were collected. By comparing the results of mNGS and conventional culture, the differences in pathogen detection rate and pathogen types were explored, and the diagnostic performance of mNGS compared to conventional culture was evaluated. Based on the various pathogens detected by mNGS, the association between clinical characteristics of bronchiectasis patients and mNGS microbiota results was analyzed. The number and types of pathogens detected by mNGS were significantly larger than those detected by conventional culture. The diagnostic efficacy of mNGS was significantly superior to conventional culture for all types of pathogens, particularly in viral detection (p < 0.01). Regarding pathogen detection rate, the bacteria with the highest detection rate were Pseudomonas aeruginosa (17/58) and Haemophilus influenzae (11/58); the fungus with the highest detection rate was Aspergillus fumigatus (10/21), and the virus with the highest detection rate was human herpes virus 4 (4/11). Differences were observed between the positive and negative groups for P. aeruginosa in terms of common scoring systems for bronchiectasis and whether the main symptom of bronchiectasis manifested as thick sputum (p < 0.05). Significant distinctions were also noted between the positive and negative groups for A. fumigatus regarding Reiff score, neutrophil percentage, bronchiectasis etiology, and alterations in treatment plans following mNGS results reporting (p < 0.05). Notably, 70% of patients with positive A. fumigatus infection opted to change their treatment plans. The correlation study between clinical characteristics of bronchiectasis patients and mNGS microbiological results revealed that bacteria, such as P. aeruginosa, and fungi, such as A. fumigatus, were associated with specific clinical features of patients. This underscored the significance of mNGS in guiding personalized treatment approaches. mNGS could identify multiple pathogens in different types of bronchiectasis samples and was a rapid and effective diagnostic tool for pathogen identification. Its use was recommended for diagnosing the causes of infections in bronchiectasis patients.

Transient stimulated Raman scattering spectroscopy and imaging.

Stimulated Raman scattering (SRS) has been developed as an essential quantitative contrast for chemical imaging in recent years. However, while spectral lines near the natural linewidth limit can be routinely achieved by state-of-the-art spontaneous Raman microscopes, spectral broadening is inevitable for current mainstream SRS imaging methods. This is because those SRS signals are all measured in the frequency domain. There is a compromise between sensitivity and spectral resolution: as the nonlinear process benefits from pulsed excitations, the fundamental time-energy uncertainty limits the spectral resolution. Besides, the spectral range and acquisition speed are mutually restricted. Here we report transient stimulated Raman scattering (T-SRS), an alternative time-domain strategy that bypasses all these fundamental conjugations. T-SRS is achieved by quantum coherence manipulation: we encode the vibrational oscillations in the stimulated Raman loss (SRL) signal by femtosecond pulse-pair sequence excited vibrational wave packet interference. The Raman spectrum was then achieved by Fourier transform of the time-domain SRL signal. Since all Raman modes are impulsively and simultaneously excited, T-SRS features the natural-linewidth-limit spectral line shapes, laser-bandwidth-determined spectral range, and improved sensitivity. With ~150-fs laser pulses, we boost the sensitivity of typical Raman modes to the sub-mM level. With all-plane-mirror high-speed time-delay scanning, we further demonstrated hyperspectral SRS imaging of live-cell metabolism and high-density multiplexed imaging with the natural-linewidth-limit spectral resolution. T-SRS shall find valuable applications for advanced Raman imaging.

Defective transfer of parental histone decreases frequency of homologous recombination by increasing free histone pools in budding yeast.

Recycling of parental histones is an important step in epigenetic inheritance. During DNA replication, DNA polymerase epsilon subunit DPB3/DPB4 and DNA replication helicase subunit MCM2 are involved in the transfer of parental histones to the leading and lagging strands, respectively. Single Dpb3 deletion (dpb3Δ) or Mcm2 mutation (mcm2-3A), which each disrupts one parental histone transfer pathway, leads to the other's predominance. However, the biological impact of the two histone transfer pathways on chromatin structure and DNA repair remains elusive. In this study, we used budding yeast Saccharomyces cerevisiae to determine the genetic and epigenetic outcomes from disruption of parental histone H3-H4 tetramer transfer. We found that a dpb3Δ mcm2-3A double mutant did not exhibit the asymmetric parental histone patterns caused by a single dpb3Δ or mcm2-3A mutation, suggesting that the processes by which parental histones are transferred to the leading and lagging strands are independent. Surprisingly, the frequency of homologous recombination was significantly lower in dpb3Δ, mcm2-3A and dpb3Δ mcm2-3A mutants, likely due to the elevated levels of free histones detected in the mutant cells. Together, these findings indicate that proper transfer of parental histones during DNA replication is essential for maintaining chromatin structure and that lower homologous recombination activity due to parental histone transfer defects is detrimental to cells.

Structural insights into the Oryza sativa cation transporters HKTs in salt tolerance.

The high-affinity potassium transporters (HKTs), selectively permeable to either Na+ alone or Na+/K+, play pivotal roles in maintaining plant Na+/K+ homeostasis. Although their involvement in salt tolerance is widely reported, the molecular underpinnings of Oryza sativa HKTs remain elusive. In this study, we elucidate the structures of OsHKT1;1 and OsHKT2;1, representing two distinct classes of rice HKTs. The dimeric assembled OsHKTs can be structurally divided into four domains. At the dimer interface, a half-helix or a loop in the third domain is coordinated by the C-terminal region of the opposite subunit. Additionally, we present the structures of OsHKT1;5 salt-tolerant and salt-sensitive variants, a key quantitative trait locus associated with salt tolerance. The salt-tolerant variant of OsHKT1;5 exhibits enhanced Na+ transport capability and displays a more flexible conformation. These findings shed light on the molecular basis of rice HKTs and provide insights into their role in salt tolerance.

Integrated genetic analysis of diabetic complications: Bioinformatics insights into foot ulcers, neuropathy and peripheral artery disease.

Diabetic foot ulcers (DFU), diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) are common complications of diabetes mellitus, while diabetic peripheral neuropathy and peripheral arterial disease contribute to the pathogenesis of diabetic foot ulcers, and the pathogenic mechanisms between these three diseases still need further investigation. The keywords 'diabetic foot ulcer', 'diabetic peripheral neuropathy' and 'atherosclerosis' were used to search for related gene sets in the GEO database. Differentially expressed genes (DEGs) were screened and analysed for GO, KEGG and enrichR functional enrichment. Potential three disease biomarkers were identified by SVM-SVM-RFE and LASSO regression analysis. The results were also validated using external datasets and discriminability was measured by area under the ROC curve (AUC). Finally, biomarkers and co-upregulated genes were analysed through the GSEA and Attie Laboratories diabetes databases. A total of 11 shared genes (KRT16, CD24, SAMD9L, SRGAP2, FGL2, GPR34, DDIT4, NFE2L3, FBLN5, ANXA3 and CPA3), two biomarkers (SAMD9L and FGL2) and one co-upregulated gene (CD24) were screened. GO and KEGG pathway analysis of DEGs, enrichr enrichment analysis of shared differential genes and GSEA analysis of biomarkers showed that these significant genes were mainly focused on vasoregulatory, inflammatory-oxidative stress and immunomodulatory pathways. In this study, we used bioinformatics to investigate the intrinsic relationship and potential mechanisms of three common lower extremity complications of diabetes and identified two pivotal genes using the LASSO model and the SVM-RFE algorithm, which will further help clinicians to understand the relationship between diabetic complications, improve the diagnosis and treatment of diabetic foot problems and help doctors to identify the potential risk factors of diabetic foot.