Lithium carbonate revitalizes tumor-reactive CD8+ T cells by shunting lactic acid into mitochondria.

The steady flow of lactic acid (LA) from tumor cells to the extracellular space via the monocarboxylate transporter symport system suppresses antitumor T cell immunity. However, LA is a natural energy metabolite that can be oxidized in the mitochondria and could potentially stimulate T cells. Here we show that the lactate-lowering mood stabilizer lithium carbonate (LC) can inhibit LA-mediated CD8+ T cell immunosuppression. Cytoplasmic LA increased the pumping of protons into lysosomes. LC interfered with vacuolar ATPase to block lysosomal acidification and rescue lysosomal diacylglycerol-PKCθ signaling to facilitate monocarboxylate transporter 1 localization to mitochondrial membranes, thus transporting LA into the mitochondria as an energy source for CD8+ T cells. These findings indicate that targeting LA metabolism using LC could support cancer immunotherapy.

Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles.

Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. Here we show that CD8+ memory T (TM) cells mobilize the carbamoyl phosphate (CP) metabolic pathway to clear ammonia, thus promoting memory development. CD8+ TM cells use ß-hydroxybutyrylation to upregulate CP synthetase 1 and trigger the CP metabolic cascade to form arginine in the cytosol. This cytosolic arginine is then translocated into the mitochondria where it is split by arginase 2 to urea and ornithine. Cytosolic arginine is also converted to nitric oxide and citrulline by nitric oxide synthases. Thus, both the urea and citrulline cycles are employed by CD8+ T cells to clear ammonia and enable memory development. This ammonia clearance machinery might be targeted to improve T cell-based cancer immunotherapies.

Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis.

Osteoarthritis (OA) is the most common joint disease. Currently there are no effective methods that simultaneously prevent joint degeneration and reduce pain1. Although limited evidence suggests the existence of voltage-gated sodium channels (VGSCs) in chondrocytes2, their expression and function in chondrocytes and in OA remain essentially unknown. Here we identify Nav1.7 as an OA-associated VGSC and demonstrate that human OA chondrocytes express functional Nav1.7 channels, with a density of 0.1 to 0.15 channels per µm2 and 350 to 525 channels per cell. Serial genetic ablation of Nav1.7 in multiple mouse models demonstrates that Nav1.7 expressed in dorsal root ganglia neurons is involved in pain, whereas Nav1.7 in chondrocytes regulates OA progression. Pharmacological blockade of Nav1.7 with selective or clinically used pan-Nav channel blockers significantly ameliorates the progression of structural joint damage, and reduces OA pain behaviour. Mechanistically, Nav1.7 blockers regulate intracellular Ca2+ signalling and the chondrocyte secretome, which in turn affects chondrocyte biology and OA progression. Identification of Nav1.7 as a novel chondrocyte-expressed, OA-associated channel uncovers a dual target for the development of disease-modifying and non-opioid pain relief treatment for OA.

Sustained AhR activity programs memory fate of early effector CD8+ T cells.

Identification of mechanisms that program early effector T cells to either terminal effector T (Teff) or memory T (Tm) cells has important implications for protective immunity against infections and cancers. Here, we show that the cytosolic transcription factor aryl hydrocarbon receptor (AhR) is used by early Teff cells to program memory fate. Upon antigen engagement, AhR is rapidly up-regulated via reactive oxygen species signaling in early CD8+ Teff cells, which does not affect the effector response, but is required for memory formation. Mechanistically, activated CD8+ T cells up-regulate HIF-1α to compete with AhR for HIF-1ß, leading to the loss of AhR activity in HIF-1αhigh short-lived effector cells, but sustained in HIF-1αlow memory precursor effector cells (MPECs) with the help of autocrine IL-2. AhR then licenses CD8+ MPECs in a quiescent state for memory formation. These findings partially resolve the long-standing issue of how Teff cells are regulated to differentiate into memory cells.

A developmental landscape of 3D-cultured human pre-gastrulation embryos.

Our understanding of how human embryos develop before gastrulation, including spatial self-organization and cell type ontogeny, remains limited by available two-dimensional technological platforms1,2 that do not recapitulate the in vivo conditions3-5. Here we report a three-dimensional (3D) blastocyst-culture system that enables human blastocyst development up to the primitive streak anlage stage. These 3D embryos mimic developmental landmarks and 3D architectures in vivo, including the embryonic disc, amnion, basement membrane, primary and primate unique secondary yolk sac, formation of anterior-posterior polarity and primitive streak anlage. Using single-cell transcriptome profiling, we delineate ontology and regulatory networks that underlie the segregation of epiblast, primitive endoderm and trophoblast. Compared with epiblasts, the amniotic epithelium shows unique and characteristic phenotypes. After implantation, specific pathways and transcription factors trigger the differentiation of cytotrophoblasts, extravillous cytotrophoblasts and syncytiotrophoblasts. Epiblasts undergo a transition to pluripotency upon implantation, and the transcriptome of these cells is maintained until the generation of the primitive streak anlage. These developmental processes are driven by different pluripotency factors. Together, findings from our 3D-culture approach help to determine the molecular and morphogenetic developmental landscape that occurs during human embryogenesis.

Glutathione S-transferase-Pi 1 protects cells from irradiation-induced death by inhibiting ferroptosis in pancreatic cancer.

Glutathione S-transferase-Pi 1 (GSTP1) is an isozyme that plays a key role in detoxification and antioxidative damage. It also confers resistance to tumor therapy. However, the specific role of GSTP1 in radiotherapy resistance in pancreatic cancer (PC) is not known. In this study, we investigated how GSTP1 imparts radioresistance in PC. The findings of previous studies and this study revealed that ionizing radiation (IR) induces ferroptosis in pancreatic cancer cells, primarily by upregulating the expression of ACSL4. Our results showed that after IR, GSTP1 prolonged the survival of pancreatic cancer cells by inhibiting ferroptosis but did not affect apoptosis. The expression of GSTP1 reduced cellular ferroptosis by decreasing the levels of ACSL4 and increasing the GSH content. These changes increase the resistance of pancreatic cancer cells and xenograft tumors to IR. Our findings indicate that ferroptosis participates in irradiation-induced cell death and that GSTP1 prevents IR-induced death of pancreatic cancer cells by inhibiting ferroptosis.

Suitable Isolation Side Chains: A Simple Strategy for Simultaneously Improving the Phototherapy Efficacy and Biodegradation Capacities of Conjugated Polymer Nanoparticles.

Utilizing one molecule to realize combinational photodynamic and photothermal therapy upon single-wavelength laser excitation, which relies on a multifunctional phototherapy agent, is one of the most cutting-edge research directions in tumor therapy owing to the high efficacy achieved over a short course of treatment. Herein, a simple strategy of "suitable isolation side chains" is proposed to collectively improve the fluorescence intensity, reactive oxygen species production, photothermal conversion efficiency, and biodegradation capacity. Both in vitro and in vivo results reveal the practical value and huge potential of the designed biodegradable conjugated polymer PTD-C16 with suitable isolation side chains in fluorescence image-guided combinational photodynamic and photothermal therapy. These improvements are achieved through manipulation of aggregated states by only side chain modification without changing any conjugated structure, providing new insight into the design of biodegradable high-performance phototherapy agents.

Dispersion-Selective Band Engineering in an Artificial Kagome Superlattice.

The relentless pursuit of band structure engineering continues to be a fundamental aspect in solid-state research. Here, we meticulously construct an artificial kagome potential to generate and control multiple Dirac bands of graphene. This unique high-order potential harbors natural multiperiodic components, enabling the reconstruction of band structures through different potential contributions. As a result, the band components, each characterized by distinct dispersions, shift in energy at different velocities in response to the variation of artificial potential. Thereby, we observe a significant spectral weight redistribution of the multiple Dirac peaks. Furthermore, the magnetic field can effectively weaken the superlattice effect and reactivate the intrinsic Dirac band. Overall, we achieve actively dispersion-selective band engineering, a functionality that would substantially increase the freedom in band design.

Association of plasma advanced glycation end-products and their soluble receptor with type 2 diabetes among Chinese adults.

AIMS: Population-based evidence regarding circulating advanced glycation end-products (AGEs) and the risk of type 2 diabetes (T2D) is conflicting and insufficient. We aimed to examine the association of plasma AGEs and plasma soluble receptors for AGEs (sRAGE) with T2D. MATERIALS AND METHODS: We conducted a hospital-based case-control study including 1072 pairs (53.9 ± 9.7 years, 56.0% male) of newly diagnosed T2D and age- and sex-matched controls. We further performed a nested case-control study within an ongoing prospective cohort consisting of 127 incident T2D cases and 381 well-matched controls (62.2 ± 5.1 years, 71.7% male). Plasma AGEs were detected using liquid chromatography-tandem mass spectrometry, and plasma sRAGE was measured by enzyme-linked immunosorbent assay. Conditional logistic regression was used to evaluate the association of plasma AGEs and sRAGE concentrations with T2D. RESULTS: Higher plasma AGEs and lower sRAGE concentrations were associated with higher odds of T2D. The multivariable-adjusted odds ratios of T2D comparing the highest with the lowest quartile levels were 3.28 (95% CI: 2.14, 5.02) for plasma AGEs and 0.25 (95% CI: 0.16, 0.39) for plasma sRAGE. Participants in the highest quartile of plasma AGEs and the lowest quartile of sRAGE concentrations had the greatest odds of T2D. The positive association of AGEs and inverse association of sRAGE with T2D risk was confirmed in the replication-nested case-control study. CONCLUSIONS: Increased circulating AGEs and decreased sRAGE concentrations were associated with elevated T2D risk. Our findings may have implications for the strategies of T2D prevention and management.

Amide Proton Transfer-Weighted MRI, Associations with Clinical Severity and Prognosis in Ischemic Strokes.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin scale (mRS) scores have important shortcomings. Amide proton transfer-weighted (APTw) imaging might offer more valuable information in ischemic strokes assessment. PURPOSE: To utilize APTw, apparent diffusion coefficient (ADC), and computed tomography perfusion (CTP) for the assessment of clinical symptom severity and 90-day prognosis in patients diagnosed with ischemic stroke. STUDY TYPE: Prospective. SUBJECTS: 61 patients (mean age 63.2 ± 9.7 years; 46 males, 15 females) with ischemic strokes were included in the study. FIELD STRENGTH/SEQUENCE: 3T/turbo spin echo (TSE) T1 -weighted imaging, T2 -weighted imaging, T2 -fluid attenuated inversion recovery (T2 -FLAIR), diffusion-weighted imaging (DWI), and single-shot TSE APTw imaging. ASSESSMENT: APTw, ADC, and CTP were used to compare patient subgroups and construct a prognostic nomogram model. STATISTICAL TESTS: Kolmogorov-Smirnov test, t-test, Mann-Whitney U test, chi-square test, Pearson correlation analysis, multivariate logistic regression analysis, decision curve analysis (DCA), receiver operating characteristic curves (ROCs). The significance threshold was set at P < 0.05. RESULTS: Correlation analysis revealed that APTw and NIHSS exhibit the highest correlation (r = -0.634, 95% confidence interval [CI] -0.418 to -0.782), surpassing that of ADC and lesion size. Multivariable analysis revealed APTw (odds ratio [OR] 0.905, 95% CI 0.845-0.970), ADC (OR 0.745, 95% CI 0.609-0.911), and infarct core-cerebral blood volume (IC-CBV) (OR 0.547, 95% CI 0.310-0.964) as potential risk factors associated with a poor prognosis. The nomogram model demonstrated the highest predictive efficacy, with an area under the curve (AUC) of 0.960 (95% CI 0.911-0.988), exceeding that of APTw, ADC, and IC-CBV individually. DATA CONCLUSION: The APTw technique holds potential value in categorizing and managing patients with ischemic stroke, offering guidance for the implementation of clinical treatment strategies. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Advances in Metabolism and Metabolic Toxicology of Quinoxaline 1,4-Di-N-oxides.

Quinoxaline 1,4-di-N-Oxides (QdNOs) have been used as synthetic antimicrobial agents in animal husbandry and aquaculture. The metabolism and potential toxicity have been also concerns in recently years. The metabolism investigations showed that there were 8 metabolites of Carbadox (CBX), 34 metabolites of Cyadox (CYA), 33 metabolites of Mequindox (MEQ), 35 metabolites of Olaquindox (OLA), and 56 metabolites of Quinocetone (QCT) in different animals. Among them, Cb3 and Cb8, M6, and O9 are metabolic residual markers of CBX, MEQ and OLA, which are associated with N → O reduction. Toxicity studies revealed that QdNOs exhibited severe tumorigenicity, cytotoxicity, and adrenal toxicity. Metabolic toxicology showed that toxicity of QdNOs metabolites might be related to the N → O group reduction, and some metabolites exhibited higher toxic effects than the precursor, which could provide guidance for further research on the metabolic toxicology of QdNOs and provide a wealth of information for food safety evaluation.

MR Spectroscopy Assessment of Daily Variations of GABA Levels within the Parietal Lobe and Anterior Cingulate Gyrus Regions of Healthy Young Adults.

BACKGROUND: The changes that occur in the gamma-aminobutyric acid (GABA) levels within specific brain regions throughout the day are less clear. PURPOSE: To evaluate the daily fluctuations of GABA levels within the parietal lobe (PL) and anterior cingulate gyrus (ACC) regions and explore their association with melatonin (MT) levels, heart rate (HR), and blood pressure. STUDY TYPE: Prospective. SUBJECTS: 26 healthy young adults (15 males and 11 females aged 22-27 years). FIELD STRENGTH/SEQUENCE: 3.0T, T1-weighted imaging, Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. ASSESSMENT: The acquired GABA signal contained the overlapping signals of macromolecules and homocarnosine, hence expressed as GABA+. The creatine (Cr) signal was applied as an endogenous reference. The GABA+, GABA+/Cr were measured at six different time points (1:00, 5:00, 9:00, 13:00, 17:00, and 21:00 hours) using MEGA-PRESS. The blood pressure, HR and sputum MT levels, were also acquired. STATISTICAL TESTS: The one-way repeated-measures analysis of variance (ANOVA) was used to evaluate the GABA, blood pressure, HR, and MT levels throughout the day. A general linear model was used to find the correlation between GABA and blood pressure, HR, and MT. P < 0.05 was statistically significant. RESULTS: Significant variations in GABA+/Cr and GABA+ levels were observed throughout the day within the PL region. The lowest levels were recorded at 9:00 hour (GABA+/Cr: 0.100 ± 0.003，GABA+:1.877 ± 0.051 i.u) and the highest levels were recorded at 21:00 hour (GABA+/Cr: 0.115 ± 0.003, GABA+:2.122 ± 0.052 i.u). The MT levels were positively correlated with GABA+/Cr (r = 0.301) and GABA+ (r = 0.312) within the ACC region. DATA CONCLUSION: GABA+/Cr and GABA+ in ACC are positively correlated with MT. GABA levels in the PL have diurnal differences. These findings may indicate that the body's GABA level change in response to the light-dark cycle. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Machine learning in prenatal MRI predicts postnatal ventricular abnormalities in fetuses with isolated ventriculomegaly.

OBJECTIVES: To evaluate the intracranial structures and brain parenchyma radiomics surrounding the occipital horn of the lateral ventricle in normal fetuses (NFs) and fetuses with ventriculomegaly (FVs), as well as to predict postnatally enlarged lateral ventricle alterations in FVs. METHODS: Between January 2014 and August 2023, 141 NFs and 101 FVs underwent 1.5 T balanced steady-state free precession (BSSFP), including 68 FVs with resolved lateral ventricles (FVM-resolved) and 33 FVs with stable lateral ventricles (FVM-stable). Demographic data and intracranial structures were analyzed. To predict the enlarged ventricle alterations of FVs postnatally, logistic regression models with 5-fold cross-validation were developed based on lateral ventricle morphology, blended-cortical or/and subcortical radiomics characteristics. Validation of the models' performance was conducted using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: Significant alterations in cerebral structures were observed between NFs and FVs (p < 0.05), excluding the maximum frontal horn diameter (FD). However, there was no notable distinction between the FVM-resolved and FVM-stable groups (all p > 0.05). Based on subcortical-radiomics on the aberrant sides of FVs, this approach exhibited high efficacy in distinguishing NFs from FVs in the training/validation set, yielding an impressive AUC of 1/0.992. With an AUC value of 0.822/0.743 in the training/validation set, the Subcortical-radiomics model demonstrated its ability to predict lateral ventricle alterations in FVs, which had the greatest predictive advantages indicated by DCA. CONCLUSIONS: Microstructural alterations in subcortical parenchyma associated with ventriculomegaly can serve as predictive indicators for postnatal lateral ventricle variations in FVs. CLINICAL RELEVANCE STATEMENT: It is critical to gain pertinent information from a solitary fetal MRI to anticipate postnatal lateral ventricle alterations in fetuses with ventriculomegaly. This approach holds the potential to diminish the necessity for recurrent prenatal ultrasound or MRI examinations. KEY POINTS: Fetal ventriculomegaly is a dynamic condition that affects postnatal neurodevelopment. Machine learning and subcortical-radiomics can predict postnatal alterations in the lateral ventricle. Machine learning, applied to single-fetal MRI, might reduce required antenatal testing.

The role of receptors in the cross-species spread of coronaviruses infecting humans and pigs.

The pandemic caused by SARS-CoV-2, which has proven capable of infecting over 30 animal species, highlights the critical need for understanding the mechanisms of cross-species transmission and the emergence of novel coronavirus strains. The recent discovery of CCoV-HuPn-2018, a recombinant alphacoronavirus from canines and felines that can infect humans, along with evidence of SARS-CoV-2 infection in pig cells, underscores the potential for coronaviruses to overcome species barriers. This review investigates the origins and cross-species transmission of both human and porcine coronaviruses, with a specific emphasis on the instrumental role receptors play in this process.

Preclinical and phase I studies of an antisense oligonucleotide drug targeting IGF-1R in liver cancer.

Aim: To evaluate a novel antisense oligonucleotide drug targeting human IGF-1R in preclinical and phase I studies of liver cancer. Materials & methods: The tolerability and safety of an investigational new drug were evaluated in a dose-escalation trial involving 17 patients with advanced liver cancer after preclinical assessment of pharmacokinetics and pharmacodynamics. Results: The drug exposure levels in the phase I trial were determined by the in vivo efficacy with pharmacokinetics evaluation in rats and rhesus monkeys. This clinical study showed that the maximum tolerated dose was 3.96 mg/kg, and the dose-limiting toxicity dose was 4.4 mg/kg. Conclusion: The drug was safe and tolerable in patients with advanced liver cancer.Clinical Trial Registration: ChiCTR2100044235 (www.chictr.org.cn).

CT102 is a potential new drug for liver cancer treatment. It belongs to a new form of medicine using gene therapy technology called antisense oligonucleotides. There are some antisense oligonucleotides approved for treating rare diseases. This study evaluated the antitumor effect, metabolism and safety of CT102 in preclinical and clinical trials. The results showed that CT102 could inhibit tumor growth in mice with liver cancer and maintain high levels in the liver. It was found that CT102 was safe and tolerable in patients with advanced liver cancer. This suggests that CT102 has therapeutic potential for liver cancer treatment. The good tolerability and safety of CT102 in patients supports further studies on liver cancer treatment.

An unusual cause of cardiac arrest in a young infant.

BACKGROUND: Anomalous aortic origin of a coronary artery from the inappropriate sinus of Valsalva (AAOCA) is a rare congenital heart lesion. It is uncommon for patients with AAOCA to present with severe symptoms at a very young age. CASE PRESENTATION: We describe a very rare but critical presentation in a young infant with AAOCA that requires surgical repair and pacemaker placement. A three-month-old infant was referred because of syncope. Cardiac arrest occurred shortly after admission. The electrocardiogram indicated a complete atrioventricular block and a transvenous temporary pacemaker was implanted. A further coronary computed tomographic angiography (CTA) showed the anomalous origin of the right coronary artery from the left sinus of Valsalva. Coronary artery unroofing was performed due to an interarterial course with the intramural component, and a permanent epicardial pacemaker was implanted. The postoperative recovery was uneventful, and this patient was thriving and asymptomatic at the nine-month follow-up. However, the electrocardiogram still indicated a complete pacing rhythm. CONCLUSIONS: By timely diagnosis and treatment, this patient is successfully rescued. Although rare, AAOCA may be fatal even in infants.

Associations of dinitroaniline herbicide exposure, genetic susceptibility, and lifestyle with glucose dysregulation: A gene-environment interaction study from the Wuhan-Zhuhai cohort.

OBJECTIVE: To assess the association of dinitroaniline herbicides as well as their interactions with genetic susceptibility and lifestyle with glucose dysregulation. METHODS: A total of 4310 Chinese urban adults from the baseline of the Wuhan-Zhuhai Cohort were included in the cross-sectional study. A follow-up panel from the cohort was included in the longitudinal study, including 158 participants with 432 observations. Glucose dysregulation, including fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), type 2 diabetes mellitus (T2DM), and impaired fasting glucose (IFG) were assessed. Serum dinitroaniline herbicides including benfluralin, trifluralin, and pendimethalin were measured. T2DM-related polygenic risk score (PRS) and healthy life scores were constructed. RESULTS: Cross-sectionally, each 2-fold increase in serum benfluralin was associated with a 1.12%, 2.03%, and 9% increase in FPG, HOMA-IR, and IFG risk, respectively. Each 2-fold increase in serum trifluralin was associated with a 0.70% increase in FPG. Each 2-fold increase in serum pendimethalin was associated with a 2.53% and 24% increase in FPG and IFG risk, respectively (all P < 0.05). Positive associations were found between the dinitroaniline herbicide mixture and glucose dysregulation. Longitudinally, serum benfluralin and pendimethalin were associated with the annual increases in FPG and HOMA-IR (P < 0.05). Joint and interaction effect analysis showed that compared with participants with high benfluralin/trifluralin/pendimethalin, high PRS, and unhealthy lifestyle, those with low benfluralin/trifluralin/pendimethalin, low PRS, and healthy lifestyle showed the greatest declines in FPG, i.e., -15.46%, -13.58%, and -10.51% changes, respectively; and the greatest reductions in IFG risks, i.e., 75%, 61%, and 73% reductions, respectively (all P < 0.05). CONCLUSIONS: This study highlighted the importance of controlling dinitroaniline herbicide exposure and following healthy lifestyles in glucose dysregulation prevention, especially among individuals with high genetic risk of T2DM.

Two laser-assisted hatching methods of embryos in ART: a systematic review and meta-analysis.

BACKGROUND: Laser-assisted hatching (LAH) stands as the predominant technique for removing the zona pellucida (ZP) in embryos, primarily consisting of two methods: drilling laser-assisted hatching (D-LAH) and thinning laser-assisted hatching (T-LAH). Presently, both methods have limitations, and their comparative efficacy for embryo implantation and clinical pregnancy remains uncertain. AIM: Evaluate the impact of D-LAH and T-LAH on clinical pregnancy rates within assisted reproductive technology (ART). METHODS: We systematically searched electronic databases including PubMed, Web of Science, and Cochrane Library until July 20, 2022. This study encompassed observational studies and randomized controlled trials (RCTs). A 95% confidence interval (CI) was utilized for assessing the risk ratio (RR) of pregnancy outcomes. The level of heterogeneity was measured using I2 statistics, considering a value exceeding 50% as indicative of substantial heterogeneity. RESULTS: The meta-analysis scrutinized 9 studies involving 2405 clinical pregnancies from D-LAH and 2239 from T-LAH. Findings suggested no considerable variation in the clinical pregnancy rates between the two techniques (RR = 0.93, 95% CI: 0.79-1.10, I2 = 71%, P = 0.41). Subgroup analyses also revealed no substantial differences. However, D-LAH exhibited a notably higher occurrence of singleton pregnancies compared to T-LAH (RR = 2.28, 95% CI: 1.08-4.82, I2 = 89%, P = 0.03). There were no noteworthy distinctions observed in other secondary outcomes encompassing implantation rate, multiple pregnancies, ongoing pregnancy, miscarriage, premature birth, and live birth. CONCLUSION: Both the primary findings and subgroup analyses showed no marked variance in clinical pregnancy rates between D-LAH and T-LAH. Therefore, patients with varying conditions should select their preferred LAH technique after assessing their individual situation. However, due to the restricted number of studies involved, accurately gauging the influence of these laser techniques on clinical outcomes is challenging, necessitating further RCTs and high-quality studies to enhance the success rate of ART. TRIAL REGISTRATION: PROSPERO: CRD42022347066.

Identification, Characteristics, and Fungicide Efficacy of Seed-Associated Fungi of Saposhnikovia divaricata in Northeast China.

Saposhnikovia divaricata (Trucz.) Schischk. is one of the traditional medicinal herbs in Northeast China, and its roots are used for medicinal purposes. In 2020, a fungus isolated from S. divaricata seeds was observed to cause root rot of seedlings and leaf and stem spot of adult plants in Shuangyashan, Heilongjiang, China. Based on morphological and molecular data, isolates of all fungi were identified as Alternaria alternata. To our knowledge, this is the first report of A. alternata isolated from S. divaricata seeds in China. The carrying rate of S. divaricata seeds from 20 different collection sites reached 100% in 70% of the sites in Hulunbeier area, Inner Mongolia, China. The A. alternata isolate could infect the roots of cucumber, sorghum, mung bean, and maize seedlings and cause root rot. Considering the control of seed-associated fungal diseases, prochloraz 45% EW had the best control effect of 92.6%, followed by flusilazole 400 g liter-1 EC (88.9%) and azoxystrobin + propiconazole 18.7% SE (70.7%) of 15 fungicides. Further field control efficacy showed that 45% prochloraz EW had an 80% control efficacy on the disease at a dose of 0.225 g liter-1. It is recommended that soaking seeds and spraying are the best treatments for controlling seed-associated fungi and leaf spot on S. divaricata caused by A. alternata. Therefore, the aforementioned methods can effectively prevent the occurrence of fungal diseases of S. divaricata and provide a way to reduce reinfestation in the field.

Evaluation of Resistance Resources and Analysis of Resistance Mechanisms of Maize to Stalk Rot Caused by Fusarium graminearum.

Stalk rot is one of the most destructive and widely distributed diseases in maize plants worldwide. Research on the performance and resistance mechanisms of maize against stem rot is constantly improving. In this study, among 120 inbred maize lines infected by Fusarium graminearum using the injection method, 4 lines (3.33%) were highly resistant to stalk rot, 28 lines (23.33%) were resistant, 57 lines (47.50%) were susceptible, and 31 lines (25.84%) were highly susceptible. The inbred lines 18N10118 and 18N10370 were the most resistant and susceptible with disease indices of 7.5 and 75.6, respectively. Treatment of resistant and susceptible maize inbred seedlings with F. graminearum showed that root hair growth of the susceptible inbred lines was significantly inhibited, and a large number of hyphae attached and adsorbed multiple conidia near the root system. However, the resistant inbred lines were delayed and inconspicuous, with only a few hyphae and spores appearing near the root system. Compared with susceptible inbred lines, resistant maize inbred line seedlings treated with F. graminearum exhibited elevated activities of catalase, phenylalanine ammonia-lyase, polyphenol oxidase, and superoxide dismutase. We identified 153 genes related to disease resistance by transcriptome analysis. The mitogen-activated protein kinase signaling and peroxisome pathways mainly regulated the resistance mechanism of maize inbred lines to F. graminearum infection. These two pathways might play an important role in the disease resistance mechanism, and the function of genes in the two pathways must be further studied, which might provide a theoretical basis for further understanding the molecular resistance mechanism of stalk rot and resistance gene mining.