Temperature and light reverse the fertility of rice P/TGMS line ostms19 via reactive oxygen species homeostasis.

P/TGMS (Photo/thermo-sensitive genic male sterile) lines are crucial resources for two-line hybrid rice breeding. Previous studies revealed that slow development is a general mechanism for sterility-fertility conversion of P/TGMS in Arabidopsis. However, the difference in P/TGMS genes between rice and Arabidopsis suggests the presence of a distinct P/TGMS mechanism in rice. In this study, we isolated a novel P/TGMS line, ostms19, which shows sterility under high-temperature conditions and fertility under low-temperature conditions. OsTMS19 encodes a novel pentatricopeptide repeat (PPR) protein essential for pollen formation, in which a point mutation GTA(Val) to GCA(Ala) leads to ostms19 P/TGMS phenotype. It is highly expressed in the tapetum and localized to mitochondria. Under high temperature or long-day photoperiod conditions, excessive ROS accumulation in ostms19 anthers during pollen mitosis disrupts gene expression and intine formation, causing male sterility. Conversely, under low temperature or short-day photoperiod conditions, ROS can be effectively scavenged in anthers, resulting in fertility restoration. This indicates that ROS homeostasis is critical for fertility conversion. This relationship between ROS homeostasis and fertility conversion has also been observed in other tested rice P/TGMS lines. Therefore, we propose that ROS homeostasis is a general mechanism for the sterility-fertility conversion of rice P/TGMS lines.

Comparison of totally robotic and totally laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.

Integrating UPLC-QTOF-MS/MS and UPLC-DAD to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the overall quality of three Si-Wu-Tang formulations.

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

Single-cell transcriptome landscape of ovarian cells during primordial follicle assembly in mice.

Primordial follicle assembly in the mouse occurs during perinatal ages and largely determines the ovarian reserve that will be available to support the reproductive life span. The development of primordial follicles is controlled by a complex network of interactions between oocytes and ovarian somatic cells that remain poorly understood. In the present research, using single-cell RNA sequencing performed over a time series on murine ovaries, coupled with several bioinformatics analyses, the complete dynamic genetic programs of germ and granulosa cells from E16.5 to postnatal day (PD) 3 were reported. Along with confirming the previously reported expression of genes by germ cells and granulosa cells, our analyses identified 5 distinct cell clusters associated with germ cells and 6 with granulosa cells. Consequently, several new genes expressed at significant levels at each investigated stage were assigned. By building single-cell pseudotemporal trajectories, 3 states and 1 branch point of fate transition for the germ cells were revealed, as well as for the granulosa cells. Moreover, Gene Ontology (GO) term enrichment enabled identification of the biological process most represented in germ cells and granulosa cells or common to both cell types at each specific stage, and the interactions of germ cells and granulosa cells basing on known and novel pathway were presented. Finally, by using single-cell regulatory network inference and clustering (SCENIC) algorithm, we were able to establish a network of regulons that can be postulated as likely candidates for sustaining germ cell-specific transcription programs throughout the period of investigation. Above all, this study provides the whole transcriptome landscape of ovarian cells and unearths new insights during primordial follicle assembly in mice.

Impaired primordial follicle assembly in offspring ovaries from zearalenone-exposed mothers involves reduced mitochondrial activity and altered epigenetics in oocytes.

Previous works have shown that zearalenone (ZEA), as an estrogenic pollutant, has adverse effects on mammalian folliculogenesis. In the present study, we found that prolonged exposure of female mice to ZEA around the end of pregnancy caused severe impairment of primordial follicle formation in the ovaries of newborn mice and altered the expression of many genes in oocytes as revealed by single-cell RNA sequencing (scRNA-seq). These changes were associated with morphological and molecular alterations of mitochondria, increased autophagic markers in oocytes, and epigenetic changes in the ovaries of newborn mice from ZEA-exposed mothers. The latter increased expression of HDAC2 deacetylases was leading to decreased levels of H3K9ac and H4K12ac. Most of these modifications were relieved when the expression of  Hdac2 in newborn ovaries was reduced by RNA interference during in vitro culture in the presence of ZEA. Such changes were also alleviated in offspring ovaries from mothers treated with both ZEA and the coenzyme Q10 (CoQ10), which is known to be able to restore mitochondrial activities. We concluded that impaired mitochondrial activities in oocytes caused by ZEA are at the origin of metabolic alterations that modify the expression of genes controlling autophagy and primordial follicle assembly through changes in epigenetic histones.

Double-lung versus heart-lung transplantation for end-stage cardiopulmonary disease: a systematic review and meta-analysis.

We compared posttransplant outcomes following double-lung transplantation (DLTx) and heart-lung transplantation (HLTx), based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. We then performed a meta-analysis of baseline characteristics and posttransplant outcomes. Subgroup analyses were implemented according to indication, publication year, and center. This study was registered on PROSPERO (number CRD42020223493). Ten studies were included in this meta-analysis, involving 1230 DLTx patients and 1022 HLTx patients. The DLTx group was characterized by older donors (P = 0.04) and a longer allograft ischemia time (P < 0.001) than the HLTx group. The two groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all P > 0.05), with similar results identified in subgroup analyses. We found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit stay and hospital stay, length of postoperative ventilation, in-hospital mortality, or surgical complications between the groups (all P > 0.05). Thus, DLTx provides similar posttransplant survival to HLTx for end-stage cardiopulmonary disease. These two procedures have a comparable risk of CLAD and other posttransplant outcomes.

Synthesis of Polydiynes via an Unexpected Dimerization/Polymerization Sequence of C3 Propargylic Electrophiles.

Here, we describe the unexpected discovery of a Cu-catalyzed condensation polymerization reaction of propargylic electrophiles (CPPE) that transforms simple C3 building blocks into polydiynes of C6 repeating units. This reaction was achieved by a simple system composed of a copper acetylide initiator and an electron-rich phosphine ligand. Alkyne polymers (up to 33.8 kg/mol) were produced in good yields and exclusive regioselectivity with high functional group compatibility. Hydrogenation of the product afforded a new polyolefin-type backbone, while base-mediated isomerization led to a new type of dienyne-based electron-deficient conjugated polymer. Mechanistic studies revealed a new α-α selective Cu-catalyzed dimerization pathway of the C3 unit, followed by in situ organocopper-mediated chain-growth propagation. These insights not only provide an important understanding of the Cu-catalyzed CPPE of C3, C4, and C6 monomers in general but also lead to a significantly improved synthesis of polydiynes from simpler starting materials with handles for the incorporation of an α-end functional group.

Mutation of glucose-methanol-choline oxidoreductase leads to thermosensitive genic male sterility in rice and Arabidopsis.

Thermosensitive genic male sterility (TGMS) lines serve as the major genetic resource for two-line hybrid breeding in rice. However, their unstable sterility under occasional low temperatures in summer highly limits their application. In this study, we identified a novel rice TGMS line, ostms18, of cultivar ZH11 (Oryza sativa ssp. japonica). ostms18 sterility is more stable in summer than the TGMS line carrying the widely used locus tms5 in the ZH11 genetic background, suggesting its potential application for rice breeding. The ostms18 TGMS trait is caused by the point mutation from Gly to Ser in a glucose-methanol-choline (GMC) oxidoreductase; knockout of the oxidoreductase was previously reported to cause complete male sterility. Cellular analysis revealed the pollen wall of ostms18 to be defective, leading to aborted pollen under high temperature. Further analysis showed that the tapetal transcription factor OsMS188 directly regulates OsTMS18 for pollen wall formation. Under low temperature, the flawed pollen wall in ostms18 is sufficient to protect its microspore, allowing for development of functional pollen and restoring fertility. We identified the orthologous gene in Arabidopsis. Although mutants for the gene were fertile under normal conditions (24°C), fertility was significantly reduced under high temperature (28°C), exhibiting a TGMS trait. A cellular mechanism integrated with genetic mutations and different plant species for fertility restoration of TGMS lines is proposed.

Silver-Rich Hybrid Framework Iodide Based on [Ag8I6]2+ Clusters Displays Low-Temperature Dual Emission and Luminescence Thermochromism.

Cluster-based framework metal iodides have diverse structures and excellent luminescence properties, and show promising applications in sensing and solid-state lighting. However, the design and synthesis of these materials remain great challenges because excess I- ions introduced into the synthesis systems decrease the condensation degree of M-I units. In this work, a new strategy is developed to control the condensation behavior of Ag-I units, and a new silver-rich cluster-based framework iodide [DabcoAg8I6(SPh)2]n (1) (Dabco = 1,4-diazabicyclo [2.2.2] octane) has been synthesized under solvothermal conditions in the presence of silver thiophenolate (AgSPh)n. Compound 1 features a three-dimensional (3-D) cluster-based framework with a pillared layer structure composed of cationic [Ag8I6]2+ clusters bridged by SPh- and Dabco, and displays low-temperature dual emission and luminescence thermochromism.

CHMFL-26 is a highly potent irreversible HER2 inhibitor for use in the treatment of HER2-positive and HER2-mutant cancers.

Oncogene HER2 is amplified in 20%-25% of human breast cancers and 6.1%-23.0% of gastric cancers, and HER2-directed therapy significantly improves the outcome for patients with HER2-positive cancers. However, drug resistance is still a clinical challenge due to primary or acquired mutations and drug-induced negative regulatory feedback. In this study, we discovered a potent irreversible HER2 kinase inhibitor, CHMFL-26, which covalently targeted cysteine 805 of HER2 and effectively overcame the drug resistance caused by HER2 V777L, HER2 L755S, HER2 exon 20 insertions, and p95-HER2 truncation mutations. CHMFL-26 displayed potent antiproliferation efficacy against HER2-amplified and mutant cells through constant HER2-mediated signaling pathway inhibition and apoptosis induction. In addition, CHMFL-26 suppressed tumor growth in a dose-dependent manner in xenograft mouse models. Together, these results suggest that CHMFL-26 may be a potential novel anti-HER2 agent for overcoming drug resistance in HER2-positive cancer therapy.

Dissecting the initiation of female meiosis in the mouse at single-cell resolution.

Meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single-cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By analysing cluster-specific gene expression profiles, we found four cell clusters correspond to different cell stages en route to meiosis and characterized their detailed transcriptome dynamics. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving female meiosis initiation.

Calf circumference predicts frailty in older adults: the Chinese longitudinal healthy longevity survey.

BACKGROUND: Although frailty is a common geriatric syndrome in old adults, a simple method to assess the degree of frailty in a person has not yet been established. In this study we have tried to establish the association between calf circumference (CC) and frailty among older Chinese people. METHODS: We used the data obtained from the 2014 edition of the Chinese Longitudinal Healthy Longevity Survey; 1216 participants aged ≥60 years were included for the study. Body mass index, CC and waist circumference measurement data, and laboratory test results were collected. Frailty status was measured using the frailty index (FI). Participants were then classified into non-frail (FI < 0.25) and frail (FI ≥ 0.25) groups. RESULTS: There were 874 participants (71.9%) in the non-frail group and 342 (28.1%) in the frail group. The CC was significantly different between the two groups (31.54 ± 4.16 versus 28.04 ± 4.53, P < 0.001). Logistic regression analysis revealed that CC (odds ratio = 0.947, 95% confidence interval: 0.904-0.993, P = 0.023) was an independent impact factor associated with frailty. The CC value of 28.5 cm was considered the best cut-off value in women with area under the curve (AUC) was 0.732 (P < 0.001) and 29.5 cm in men with AUC was 0.592 (P = 0.004);We created a simple prediction model for frailty that included age,sex and CC:[Formula: see text]P = elogit(P) /1 + elogit(P), and AUC is 0.849 (P < 0.001). CONCLUSIONS: CC is a convenient and predictable marker of frailty in older adults.

Multispecies comparative analysis reveals transcriptional specificity during Mongolian horse testicular development.

Mongolian horses have been bred and used for labor and transport for centuries. Nevertheless, traits of testicular development in Mongolian horses have rarely been studied; particularly, studies regarding the transcriptional regulation characteristics of testicular development are lacking. In this paper, transcription specificity during testicular development in Mongolian horses is highlighted via a multispecies comparative analysis and weighted gene co-expression network analysis (WGCNA). Interestingly, the results showed that most genes were up-regulated in the testes after sexual maturity, which is a phenomenon conserved across species. Moreover, we observed nine key genes involved in regulating Mongolian horse testicular development. Notably, unique transcription signatures of testicular development in Mongolian horses are emphasized, which provides a novel insight into the mechanistic study of their testicular development.

Titanium(IV)-Mediated Ring-Opening/Dehydroxylative Cross-Coupling of Diaryl-Substituted Methanols with Cyclopropanol Derivatives.

A titanium(IV)-mediated ring-opening/dehydroxylative cross-coupling of diaryl-substituted methanols with a cyclopropanol derivative was developed. The reactions proceeded efficiently to provide synthetically useful γ,γ-diaryl esters in moderate to good yields, which could be applied to the functionalization of complex molecules derived from bioactive fenofibrate and isoxepac and the synthesis of a precursor of Zoloft.

Pre- and postoperative heart rate variability and vagus nerve stimulation in patients with drug-resistant epilepsy - A meta-analysis.

OBJECTIVE: The effect of vagus nerve stimulation (VNS), an important auxiliary therapy for treating drug-resistant epilepsy (DRE), on autonomic nerve function is still controversial. Heart rate variability is a widely used indicator of autonomic nerve function. To clarify the relationship between VNS and heart rate variability (HRV), we performed a meta-analysis to systematically evaluate the effect of VNS on HRV in patients with epilepsy. METHODS: We performed a systematic review by searching the following online databases: PubMed, Web of Science, EMBASE and the Cochrane Library. The key search terms were "vagal nerve stimulation," "epilepsy" and "heart rate variability". Other features of VNS in patients with epilepsy include postoperative changes in low-frequency (LF), high-frequency (HF) and low-frequency/high-frequency (LF/HF) heart rate variability, which were used as evaluation indices, and the Newcastle-Ottawa Quality Assessment Scale and Stata 14.0 statistical software were used for literature quality evaluation and meta-analysis. RESULTS: Twelve studies published in English were obtained, and 229 patients with epilepsy who underwent VNS were ultimately included after elimination of duplicate articles and those that did not meet the inclusion criteria. Regarding LF heart rate variability, in the response subgroup, patients with DRE with VNS presented a lower value (-0.58) before surgery than after surgery, with a 95% confidence interval (CI) ranging from -1.00 to -0.15. For HF heart rate variability, patients with DRE with VNS had a lower value (-0.45) before surgery than after surgery in the response subgroup, with a 95% CI ranging from -0.74 to -0.17. No differences were found for LF/HF values or the LF and HF values of other subgroups. CONCLUSION: VNS has little effect on the balance of sympathetic and parasympathetic nerve activity and would not be expected to cause cardiovascular autonomic dysfunction in patients with DRE. For patients with DRE, VNS can control seizures and has little effect on autonomic nervous function.

Mitochondria-targeted Re(I) complexes bearing guanidinium as ligands and their anticancer activity.

As the "powerhouse" of a cell, mitochondria maintain energy homeostasis, synthesize ATP via oxidative phosphorylation, generate ROS signaling molecules, and modulate cell apoptosis. Herein, three Re(I) complexes bearing guanidinium derivatives have been synthesized and characterized. All of these complexes exhibit moderate anticancer activity in HepG2, HeLa, MCF-7, and A549 cancer cells. Mechanism studies indicate that complex 3, [Re(CO)3(L)(Im)](PF6)2, can selectively localize in the mitochondria and induce cancer cell death through mitochondria-associated pathways. In addition, complex 3 can effectively depress the ability of cell migration, cell invasion, and colony formation.

Review of psychological stress on oocyte and early embryonic development in female mice.

Psychological stress can cause adverse health effects in animals and humans. Accumulating evidence suggests that psychological stress in female mice is associated with ovarian developmental abnormalities accompanied by follicle and oocyte defects. Oocyte and early embryonic development are impaired in mice facing psychological stress, likely resulting from hormone signalling disorders, reactive oxygen species (ROS) accumulation and alterations in epigenetic modifications, which are primarily mediated by the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-ovarian (HPO) axes. The present evidence suggests that psychological stress is increasingly becoming the most common causative factor for female subfertility. Here, we review recent progress on the impact of psychological stress on female reproduction, particularly for oocyte and early embryonic development in female mice. This review highlights the connection between psychological stress and reproductive health and provides novel insight on human subfertility.

Triterpenoids Extracted from Rhus chinensis Mill Act Against Colorectal Cancer by Inhibiting Enzymes in Glycolysis and Glutaminolysis: Network Analysis and Experimental Validation.

Background: Rhus chinensis Mill is a traditional Chinese medicine (TCM) mostly used to treat several cancer types. Although previous studies have found that certain ingredients of R. chinensis such as flavonoids can inhibit tumor cell proliferation [e.g. colorectal cancer (CRC)], systematic research on the mechanism underlying anticancer effect of active compounds like triterpenoids (TER) is lacking.Study Design: Herein, the concept of "network pharmacology primarily based on active compounds" was applied to explore the anticancer mechanisms of TER extract from R. chinensis. In this regard, potential targets and pathways of glycolysis and glutaminolysis form the basis for the anti-CRC effect of triterpenoids. Network pharmacology was used to predict several key proteins in the metabolic pathways, which were further verified via western blot and metabolomics methods.Results: Our results showed that the total TER in R. chinensis remarkably inhibited the proliferation and apoptosis of SW620 cells. The top 4 compounds of TER (viz., betulinic acid-BTA, betulonic acid-BTOA, betulin-BT, and semialactic acid-SA) were confirmed through the detection of UPLC-MS and analysis of cell proliferation assays. Mechanistically, this study revealed that TER plays an anti-CRC role through key targets, such as ENO1, ALDOA, PFKFB3, PKM2, and LDHA, as well as key glycolytic and glutaminolytic pathways.Conclusion: Collectively, these results have provided new insights into the mechanism underlying anti-CRC effect of triterpenoids extract obtained from R. chinensis, mainly through combination of compositional quantitative analysis, network pharmacology, and experimental verification.

Luminescent Thermochromic Silver Iodides as Wavelength-Dependent Thermometers.

Luminescent thermochromic materials with a dramatic shift of emission band under different temperatures are highly desirable in temperature sensing fields. However, the design of the synthesis of such compounds remains a great challenge. In this work, two new luminescent thermochromic silver iodides, (emIm)Ag3I4 (1) and (emIm)Ag2I3 (2) (emIm = 1-ethyl-3-methyl imidazole), have been synthesized under solvothermal conditions. Compound 1 features a [Ag3I4]- anionic layer, while compound 2 possesses an infinite [Ag2I3]- chain structure, both of which are charge balanced by emIm+ cations. Particularly, they display luminescent thermochromism with a significant wavelength shift of emission maximum with temperature change. They represent rare examples of infinite layered or chain silver iodides that show luminescent thermochromism. Furthermore, the results indicate that compounds 1 and 2 are promising wavelength-dependent luminescent thermometers.

A Double-Edged Sword: Complement Component 3 in Toxoplasma gondii Infection.

Sprague Dawley rats and Kunming (KM) mice are artificially infected with type II Toxoplasma gondii strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. The aim is to explore the mechanism of differential susceptibility of mice and rats to T. gondii infection. Therefore, a strategy of isobaric tags for relative and absolute quantitation (iTRAQ) is established to identify differentially expressed proteins (DEPs) in the rats' and the mice's brains compared to the healthy groups. In KM mice, which is susceptible to T. gondii infection, complement component 3 (C3) is upregulated and the tight junction (TJ) pathway shows a disorder. It is presumed that T. gondii-stimulated C3 disrupts the TJ of the blood-brain barrier in the CNS. This effect allows more T. gondii passing to the brain through the intercellular space.