Transcriptomic mapping uncovers Purkinje neuron plasticity driving learning.

Cellular diversification is critical for specialized functions of the brain including learning and memory1. Single-cell RNA sequencing facilitates transcriptomic profiling of distinct major types of neuron2-4, but the divergence of transcriptomic profiles within a neuronal population and their link to function remain poorly understood. Here we isolate nuclei tagged5 in specific cell types followed by single-nucleus RNA sequencing to profile Purkinje neurons and map their responses to motor activity and learning. We find that two major subpopulations of Purkinje neurons, identified by expression of the genes Aldoc and Plcb4, bear distinct transcriptomic features. Plcb4+, but not Aldoc+, Purkinje neurons exhibit robust plasticity of gene expression in mice subjected to sensorimotor and learning experience. In vivo calcium imaging and optogenetic perturbation reveal that Plcb4+ Purkinje neurons have a crucial role in associative learning. Integrating single-nucleus RNA sequencing datasets with weighted gene co-expression network analysis uncovers a learning gene module that includes components of FGFR2 signalling in Plcb4+ Purkinje neurons. Knockout of Fgfr2 in Plcb4+ Purkinje neurons in mice using CRISPR disrupts motor learning. Our findings define how diversification of Purkinje neurons is linked to their responses in motor learning and provide a foundation for understanding their differential vulnerability to neurological disorders.

Developmental programming and lineage branching of early human telencephalon.

The dorsal and ventral human telencephalons contain different neuronal subtypes, including glutamatergic, GABAergic, and cholinergic neurons, and how these neurons are generated during early development is not well understood. Using scRNA-seq and stringent validations, we reveal here a developmental roadmap for human telencephalic neurons. Both dorsal and ventral telencephalic radial glial cells (RGs) differentiate into neurons via dividing intermediate progenitor cells (IPCs_div) and early postmitotic neuroblasts (eNBs). The transcription factor ASCL1 plays a key role in promoting fate transition from RGs to IPCs_div in both regions. RGs from the regionalized neuroectoderm show heterogeneity, with restricted glutamatergic, GABAergic, and cholinergic differentiation potencies. During neurogenesis, IPCs_div gradually exit the cell cycle and branch into sister eNBs to generate distinct neuronal subtypes. Our findings highlight a general RGs-IPCs_div-eNBs developmental scheme for human telencephalic progenitors and support that the major neuronal fates of human telencephalon are predetermined during dorsoventral regionalization with neuronal diversity being further shaped during neurogenesis and neural circuit integration.

The SOC1 gene plays an important role in regulating litchi flowering time.

Litchi (Litchi chinensis Sonn.) is a valuable subtropical fruit tree with high-quality fruit. However, its economic benefits and sustainable development are restrained by a number of challenges. One major challenge is the lack of extremely early and late maturing high-quality varieties due to limited availability of varieties suitable for commercial cultivation and outdated breeding methods, resulting in an imbalanced supply and low price of litchi. Flowering time is a crucial genetic factor influencing the maturation period of litchi. Our previous research has highlighted the pivotal role of the LcFT1 gene in regulating the flowering time of litchi and identified a gene associated with LcFT1 (named as LcSOC1) based on RNA-Seq and weight gene co-expression network (WGCNA) analysis. This study further investigated the function of LcSOC1. Subcellular localization analysis revealed that LcSOC1 is primarily localized in the nucleus, where it acts as a transcription factor. LcSOC1 overexpression in Nicotiana tabacum and Arabidopsis thaliana resulted in significant early flowering. Furthermore, LcSOC1 was found to be expressed in various tissues, with the highest expression in mature leaves. Analysis of spatial and temporal expression patterns of LcSOC1 in litchi varieties with different flowering time under low temperature treatment and across an annual cycle demonstrated that LcSOC1 is responsive to low temperature induction. Interestingly, early maturing varieties exhibited higher sensitivity to low temperature, with significantly premature induction of LcSOC1 expression relative to late maturing varieties. Activation of LcSOC1 triggered the transition of litchi into the flowering phase. These findings demonstrate that LcSOC1 plays a pivotal role in regulating the flowering process and determining the flowering time in litchi. Overall, this study provides theoretical guidance and important target genes for molecular breeding to regulate litchi production period.

Do we need reshape rTNM staging system for ipsilateral breast tumor recurrence of breast cancer? A population-based, propensity score matched cohort study.

BACKGROUND: The aim of the study was to explore the role of recurrent TNM (rTNM) staging in predicting prognosis for ipsilateral breast tumor recurrence (IBTR) and determine the optimal treatment strategy for IBTR. METHOD: IBTR cases were identified from the Surveillance, Epidemiology, and End Results (SEER) database spanning the years 2000-2018. Cox proportional hazards analysis was performed to examine factors associated with overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) was employed to match IBTR with primary early breast cancer (EBC) based on clinicopathological characteristics. Investigations into the impact of different therapies were also included. RESULTS: Of the 4375 IBTR cases included in the study, the 5-year OS was 87.1%, 71.6% and 58.7% in rTNM stages I, II and III, respectively. After PSM, while IBTR patients had worse survival to primary EBC patients, prognosis of IBTR for different rTNM stage always closely aligned with the corresponding stage of primary EBC. Repeat breast-conserving surgery (BCS) with radiation therapy was equivalent to mastectomy with respect to OS and BCSS. Chemotherapy was favorable for OS and BCSS in estrogen receptor (ER)-negative IBTR or IBTR occurring within a 60-month interval. CONCLUSIONS: rTNM staging system has an outstanding prognostic value for survival outcome of patients with IBTR, and IBTR and primary EBC may have potentially analogous features in the context of TNM staging. BCS plus radiation therapy may be an alternative. IBTR cases who have experienced recurrence with short intervals and with ER-negative tumors might benefit from chemotherapy.

Oxidants Controlled C-H Bond Functionalization of N-Aryltetrahydroisoquinolines: The Construction of the Quaternary Carbon Center and Cleavage of the C-N Bond.

Initiated by triarylamine radical cation salt (TBPA), the direct C-H bond functionalization of α-N-aryltetrahydroisoquinoline esters was smoothly realized, giving a series of α-hydroxylated derivatives with a quaternary carbon center in good yields. Differently, in the presence of tert-butyl nitrite (TBN), the C-N single bond was cleaved to keto esters. The mechanistic study revealed that these reactions were mediated by a similar mechanism, in which the N-nitrosation might provide a driving force to the C-N bond cleavage.

CBr4 as a Mild Oxidant-Enabled Oxidation of a sp3 C-H Bond: A Facile Synthesis of the Persistent Iminium Salts of Tetrahydroisoquinolines.

Using CBr4 as a mild oxidant, the direct C-H bond oxidation of N-aryltetrahydroisoquinolines was achieved, giving a series of the corresponding iminium salts in high yields under metal- and photo-free reaction conditions. This reaction is superior in high yields and good functional group tolerance, and the late-stage derivatization showed that these iminium salts can readily be applied to the synthesis of the functionalized THIQs.

Efficacy analysis of tip-flexible suction access sheath during flexible ureteroscopic lithotripsy for unilateral upper urinary tract calculi.

PURPOSE: This study aims to evaluate the efficacy of tip-flexible suctioning ureteral access sheath (TFS-UAS) compared to traditional ureteral access sheath (T-UAS) in flexible ureteroscopic lithotripsy (FURL) for unilateral upper urinary tract calculi. METHODS: The study retrospectively compared outcomes from 103 cases using TFS-UAS and 138 using T-UAS treated with FURL for unilateral upper urinary tract calculi from January to October 2023. Assessed parameters included patient demographics, stone characteristics, preoperative urine cultures, ureteral pre-stenting, comorbidities, procedure time, stone-free rate (SFR), utilization of stone retrieval baskets, and postoperative Systemic Inflammatory Response Syndrome (SIRS) rates. The maximum angle of deflection was also measured when the flexible ureteroscope was located in different parts of the TFS-UAS with different diameters in vitro. RESULTS: The TFS-UAS group achieved a higher Immediate SFR (76.70% vs. 63.77%, p = 0.031) and final SFR (89.32% vs. 73.91%, p = 0.003) than the T-UAS group, especially in the lower calyx stones (80.00% vs. 41.18%, p = 0.018) and upper urinary tract calculi with a cumulative diameter of 2 cm or larger (68.97% vs. 42.11%, p = 0.029). Notably, TFS-UAS with a 10 French (F) inside diameter size achieved a higher SFR (88.57% vs. 70.59%, p = 0.041) and a greater deflection angle than the 12.5 F inside diameter size. No significant variations were observed in the operative duration, hospitalization duration and the occurrence of SIRS between the compared cohorts. CONCLUSION: TFS-UAS significantly improves SFR in FURL treatment of unilateral upper urinary tract calculi, particularly for stones located in the lower calyx or with a cumulative diameter of 2 cm or greater, compared to T-UAS.

Indium Promotes Direct Sulfonamidation of Unactivated Alcohols.

An improved protocol has been developed for the direct sulfonamidation of unactivated alkyl alcohols using In(OTf)3 as a Lewis acid catalyst. Although the established methods using Lewis or Brønsted acids have been well-studied for the direct functionalization of alcohols, their substrate scope mainly focuses on the π-activated alcohols. In this reaction, unactivated aliphatic alcohols were evaluated and afforded the desired sulfonamide products with good to excellent yields.

Organic Bases as the Organic Electron Donors (OED) Promoted Reductive Coupling of Diarylhalomethanes: Halogens Controlled Construction of Tetraarylethylenes and Tetraarylethanes.

Using the organic base as the organic electron donors, the reductive coupling of diaryhalomethanes was smoothly achieved under transition-metal-free reaction conditions, giving a series of synthetically important tetraarylethylenes and tetraarylethanes in high yields. The mechanistic study revealed that the organic bases acting as the electron donor initiated the generation of a radical intermediate, realizing the construction of tetraarylethylene and tetraarylethane skeletons.

Single-Electron Reduction of "Push-Pull" C-C Single Bond and Decyanation Using Tertiary Amines as the Organic Electron Donor.

Using commercially available tertiary amines as an organic electron donor (OED), the reduction of "push-pull" C-C single bond and reductive decyanation of tetrahydroisoquinolines were realized. These reactions exhibited higher reaction efficiency and better functional group tolerance compared with those of metallic reductants, and the mechanistic study indicated that a radical intermediate was involved in the reduction of the C-C single bond, which provides a new way to the OED-enabled mild reduction.

A novel post-percutaneous nephrolithotomy sepsis prediction model using machine learning.

OBJECTIVES: To establish a predictive model for sepsis after percutaneous nephrolithotomy (PCNL) using machine learning to identify high-risk patients and enable early diagnosis and intervention by urologists. METHODS: A retrospective study including 694 patients who underwent PCNL was performed. A predictive model for sepsis using machine learning was constructed based on 22 preoperative and intraoperative parameters. RESULTS: Sepsis occurred in 45 of 694 patients, including 16 males (35.6%) and 29 females (64.4%). Data were randomly segregated into an 80% training set and a 20% validation set via 100-fold Monte Carlo cross-validation. The variables included in this study were highly independent. The model achieved good predictive power for postoperative sepsis (AUC = 0.89, 87.8% sensitivity, 86.9% specificity, and 87.4% accuracy). The top 10 variables that contributed to the model prediction were preoperative midstream urine bacterial culture, sex, days of preoperative antibiotic use, urinary nitrite, preoperative blood white blood cell (WBC), renal pyogenesis, staghorn stones, history of ipsilateral urologic surgery, cumulative stone diameters, and renal anatomic malformation. CONCLUSION: Our predictive model is suitable for sepsis estimation after PCNL and could effectively reduce the incidence of sepsis through early intervention.

The association between high-oxygen saturation and prognosis for intracerebral hemorrhage.

BACKGROUND: Concerns about the adverse effects of excessive oxygen have grown over the years. This study investigated the relationship between high oxygen saturation and short-term prognosis of patients with spontaneous intracerebral hemorrhage (sICH) after liberal use of oxygen. METHODS: This retrospective cohort study collected data from the Medical Information Mart for Intensive Care III (MIMIC-III) database (ICU cohort) and a tertiary stroke center (general ward cohort). The data on pulse oximetry-derived oxygen saturation (SpO2) during the first 24 h in ICU and general wards were respectively extracted. RESULTS: Overall, 1117 and 372 patients were included in the ICU and general ward cohort, respectively. Among the patients from the ICU cohort, a spoon-shaped association was observed between minimum SpO2 and the risk of in-hospital mortality (non-linear P<0.0001). In comparison with minimum SpO2 of 93-97%, the minimum SpO2>97% was associated with a significantly higher risk of in-hospital mortality after adjustment for confounders. Sensitivity analysis conducted using propensity score matching did not change this significance. The same spoon-shaped association between minimum SpO2 and the risk of in-hospital mortality was also detected for the general ward cohort. In comparison with the group with 95-97% SpO2, the group with SpO2>97% showed a stronger association with, but non-significant risk for, in-hospital mortality after adjustment for confounders. The time-weighted average SpO2>97% was associated significantly with in-hospital mortality in both cohorts. CONCLUSION: Higher SpO2 (especially a minimum SpO2>97%) was unrewarding after liberal use of oxygen among patients with sICH and might even be potentially detrimental.

Anthracene-induced formation of highly twisted metallacycle and its crystal structure and tunable assembly behaviors.

Polycyclic aromatic hydrocarbons (PAHs) continue to attract increasing interest with respect to their applications as luminescent materials. The ordered structure of the metal-organic complex facilitates the selective integration of PAHs that can be tuned to function cooperatively. Here, a unique highly twisted anthracene-based organoplatinum metallacycle was prepared via coordination-driven self-assembly. Single-crystal X-ray diffraction analysis revealed that the metallacycle was twisted through the cooperation of strong π···π stacking interactions and steric hindrance between two anthracene-based ligands. Notably, the intramolecular twist and aggregation behavior introduced restrictions to the conformational change of anthracenes, which resulted in increased emission intensity of the metallacycle in solution. The emission behaviors and suprastructures based on the highly twisted metallacycle can be modulated by the introduction of different solvents. This study demonstrates that this metallacycle with highly twisted structure is a promising candidate for sensing and bioimaging applications.

The role of periodontitis in the development of atherosclerotic cardiovascular disease in participants with the components of metabolic syndrome: a systematic review and meta-analysis.

OBJECTIVES: Prevention of atherosclerotic cardiovascular disease (ASCVD) is important in individuals with metabolic syndrome components (MetS), and periodontitis may play an important role in this process. This study aims to evaluate the association between periodontitis and ASCVD in participants with the components of MetS, including obesity, dysglycemia, hypertension, and dyslipidemia. MATERIALS AND METHODS: This study conducted followed the MOOSE reporting guidelines and the PRISMA 2020 guidelines. EMBASE, MEDLINE, Web of Science, Cochrane Library, PubMed and OpenGrey were searched for observational studies about the linkage of periodontitis to ASCVD in people with MetS components up to April 9, 2023. Cohort, case-control and cross-sectional studies were included after study selection. Quality evaluation was carried out using the original and modified Newcastle-Ottawa Scale as appropriate. Random-effects model was employed for meta-analysis. RESULTS: Nineteen studies were finally included in the quality analysis, and all of them were assessed as moderate to high quality. Meta-analyses among fifteen studies revealed that the participants with periodontitis were more likely to develop ASCVD in those who have dysglycemia (RR = 1.25, 95% CI = 1.13-1.37; p < 0.05), obesity (RR = 1.13, 95% CI = 1.02-1.24; p < 0.05), dyslipidemia (RR = 1.36, 95% CI = 1.13-1.65; p < 0.05), or hypertension (1.20, 95% CI = 1.05-1.36; p < 0.05). CONCLUSIONS: Periodontitis promotes the development of ASCVD in participants with one MetS component (obesity, dysglycemia, hypertension or dyslipidemia). CLINICAL RELEVANCE: In people with MetS components, periodontitis may contribute to the ASCVD incidence.

Genetic Diversity and Genome-Wide Association Analysis of the Hulled/Naked Trait in a Barley Collection from Shanghai Agricultural Gene Bank.

Barley is one of the most important cereal crops in the world, and its value as a food is constantly being revealed, so the research into and the use of barley germplasm are very important for global food security. Although a large number of barley germplasm samples have been collected globally, their specific genetic compositions are not well understood, and in many cases their origins are even disputed. In this study, 183 barley germplasm samples from the Shanghai Agricultural Gene Bank were genotyped using genotyping-by-sequencing (GBS) technology, SNPs were identified and their genetic parameters were estimated, principal component analysis (PCA) was preformed, and the phylogenetic tree and population structure of the samples were also analyzed. In addition, a genome-wide association study (GWAS) was carried out for the hulled/naked grain trait, and a KASP marker was developed using an associated SNP. The results showed that a total of 181,906 SNPs were identified, and these barley germplasm samples could be roughly divided into three categories according to the phylogenetic analysis, which was generally consistent with the classification of the traits of row type and hulled/naked grain. Population structure analysis showed that the whole barley population could be divided into four sub-populations (SPs), the main difference from previous classifications being that the two-rowed and the hulled genotypes were sub-divided into two SPs. The GWAS analysis of the hulled/naked trait showed that many associated loci were unrelated to the Nud/nud locus, indicating that there might be new loci controlling the trait. A KASP marker was developed for one exon-type SNP on chromosome 7. Genotyping based on the KASP assay was consistent with that based on SNPs, indicating that the gene of this locus might be associated with the hulled/naked trait. The above work not only lays a good foundation for the future utilization of this barley germplasm population but it provides new loci and candidate genes for the hulled/naked trait.

Mapping of a Major-Effect Quantitative Trait Locus for Seed Dormancy in Wheat.

The excavation and utilization of dormancy loci in breeding are effective endeavors for enhancing the resistance to pre-harvest sprouting (PHS) of wheat varieties. CH1539 is a wheat breeding line with high-level seed dormancy. To clarify the dormant loci carried by CH1539 and obtain linked molecular markers, in this study, a recombinant inbred line (RIL) population derived from the cross of weak dormant SY95-71 and strong dormant CH1539 was genotyped using the Wheat17K single-nucleotide polymorphism (SNP) array, and a high-density genetic map covering 21 chromosomes and consisting of 2437 SNP markers was constructed. Then, the germination percentage (GP) and germination index (GI) of the seeds from each RIL were estimated. Two QTLs for GP on chromosomes 5A and 6B, and four QTLs for GI on chromosomes 5A, 6B, 6D and 7A were identified. Among them, the QTL on chromosomes 6B controlling both GP and GI, temporarily named QGp/Gi.sxau-6B, is a major QTL for seed dormancy with the maximum phenotypic variance explained of 17.66~34.11%. One PCR-based diagnostic marker Ger6B-3 for QGp/Gi.sxau-6B was developed, and the genetic effect of QGp/Gi.sxau-6B on the RIL population and a set of wheat germplasm comprising 97 accessions was successfully confirmed. QGp/Gi.sxau-6B located in the 28.7~30.9 Mbp physical position is different from all the known dormancy loci on chromosomes 6B, and within the interval, there are 30 high-confidence annotated genes. Our results revealed a novel QTL QGp/Gi.sxau-6B whose CH1539 allele had a strong and broad effect on seed dormancy, which will be useful in further PHS-resistant wheat breeding.

C-H Bond Activation Relay (CHAR) of Proline Ester Derivatives Promoted by In Situ Triarylamine Radical Cation: Selective Synthesis of 4-Bromopyrrole Derivatives.

Using the in situ generated triarylamine radical cation as an initiator, the sp3 C-H bond of proline esters was smoothly oxidized and brominated through C-H activation relay (CHAR), giving a series of 4-bromopyrroles in good yields with high regioselectivity. The mechanistic study revealed that the oxidation of the active C-H bond initiated the followed 1,5-HAT and bromination, which provides a new method to realize the functionalization of the remote C-H bond.

Barley Grass Juice Attenuates Hydrodynamic Transfection-Induced HCC Initiation in Mice.

Barley (Hordeum vulgare L.) grass has been recognized as a functional food with a wide spectrum of health-promoting properties. Supplementation with barley grass has the potential to prevent chronic diseases, such as cancer. Here, we investigated whether barley grass could protect against hepatocellular carcinoma (HCC). Our data showed that administration of barley grass juice attenuates tumor development in a hydrodynamic gene delivery-induced model of HCC. The expression levels of the immune cell markers Ptprc and Adgre1 were upregulated in the barley grass juice-treated and normal groups, compared to those in the vehicle group in the HCC model. Immune cells (CD45+, F4/80+, and CLEC4F + iNOS + cells) infiltration in the liver increased following barley grass juice administration. Our results indicate that barley grass could be beneficial for HCC alleviation, partly by regulating immune cell infiltration. The ingredients of barley grass affect immune cell infiltration in HCC, and the detailed mechanism requires further study.

Development and validation of the UCSS score, a novel method to predict septic shock after PCNL.

OBJECTIVE: To develop an objective and easily recognizable model to predict septic shock following percutaneous nephrolithotomy (PCNL). SUBJECTS AND METHODS: First, we identified differences between 431 patients who underwent PCNL with or without septic shock. These data were used to develop existing models and examine their improvement. Multivariate analysis was applied to identify risk factors of septic shock after PCNL based on the scores allocated to the PCNL postoperative test indicators. Finally, we developed a predictive nomogram using the selected factors and compared its performance with that of the existing nomograms SOFA, qSOFA, and SIRS. RESULTS: Twelve (2.8%) of the patients met the criteria for postoperative septic shock after PCNL. Baseline data analysis revealed differences in sex, preoperative drainage, urinary culture, and urinary leukocyte between groups. After transforming patient data into measurement-level data, we investigated each index score in these conditions, and found that the incidence of septic shock generally increased with the score. Multivariate analysis and early optimization screening revealed that septic shock factors could be predicted using platelets, leukocytes, bilirubin, and procalcitonin levels. We further compared the prediction accuracy of urinary calculi-associated septic shock (UCSS), SOFA, qSOFA, and SIRS scores using the AUC of the ROC curve. As compared to SIRS [AUC 0.938 (95% CI 0.910-0.959)] and qSOFA [AUC 0.930 (95% CI 0.901-0.952)], UCSS [AUC 0.974 (95% Cl 0.954-0.987)] and SOFA [AUC 0.974 (95% CI 0.954-0.987)] scored better at discriminating septic shock after PCNL. We further compared the ROC curves of UCSS with SOFA (95% CI - 0.800 to 0.0808, P = 0.992), qSOFA (95% CI - 0.0611 to 0.0808, P = 0.409), and SIRS (95% CI - 0.0703 to 0.144, P = 0.502), finding that UCSS was non-inferior to these models. CONCLUSIONS: UCSS, a new convenient and cost-effective model, can predict septic shock following PCNL and provide more accurate discriminative and corrective capability than existing models by including only objective data. The predictive value of UCSS for septic shock after PCNL was greater than that of qSOFA or SIRS scores.

Halogen Bond (XB) Promoted α-Tribromomethylation of N-Aryltetrahydroisoquinolines and Further Cyclization to 5,6-Dihydroindolo[2,1-a]isoquinolines.

Using CBr4 as a halogen bond donor and the source of tribromomethyl group, a halogen bond promoted tribromomethylation of N-aryltetrahydroisoquinolines was achieved. This reaction was also extended to the construction of the dibenzopyrrocoline alkaloid skeleton through a one-pot process. The mechanistic study confirmed the existence of the halogen bond.