EGFR signaling controls directionality of epithelial multilayer formation upon loss of cell polarity.

Apical-basal polarity is maintained by distinct protein complexes that reside in membrane junctions, and polarity loss in monolayered epithelial cells can lead to formation of multilayers, cell extrusion, and/or malignant overgrowth. Yet, how polarity loss cooperates with intrinsic signals to control directional invasion toward neighboring epithelial cells remains elusive. Using the Drosophila ovarian follicular epithelium as a model, we found that posterior follicle cells with loss of lethal giant larvae (lgl) or Discs large (Dlg) accumulate apically toward germline cells, whereas cells with loss of Bazooka (Baz) or atypical protein kinase C (aPKC) expand toward the basal side of wildtype neighbors. Further studies revealed that these distinct multilayering patterns in the follicular epithelium were determined by epidermal growth factor receptor (EGFR) signaling and its downstream target Pointed, a zinc-finger transcription factor. Additionally, we identified Rho kinase as a Pointed target that regulates formation of distinct multilayering patterns. These findings provide insight into how cell polarity genes and receptor tyrosine kinase signaling interact to govern epithelial cell organization and directional growth that contribute to epithelial tumor formation.

Eccentricity-paced geomagnetic field and monsoon rainfall variations over the last 870 kyr.

Whether there are links between geomagnetic field and Earth's orbital parameters remains unclear. Synchronous reconstructions of parallel long-term quantitative geomagnetic field and climate change records are rare. Here, we present 10Be-derived changes of both geomagnetic field and Asian monsoon (AM) rainfall over the last 870 kyr from the Xifeng loess-paleosol sequence on the central Chinese Loess Plateau. The 10BeGM flux (a proxy for geomagnetic field-induced 10Be production rate) reveals 13 consecutive geomagnetic excursions in the Brunhes chron, which are synchronized with the global records, providing key time markers for Chinese loess-paleosol sequences. The 10Be-derived rainfall exhibits distinct ~100 kyr glacial-interglacial cycles, and superimposed precessional (~23 kyr) cycles that match with those in Chinese speleothem δ18O record. We find that changes in the geomagnetic field and AM rainfall share a common ~100 kyr cyclicity, implying a likely eccentricity modulation of both the geomagnetic field and climate.

Alzheimer-like behavior and synaptic dysfunction in 3 × Tg-AD mice are reversed with calcineurin inhibition.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Current treatments are unable to achieve satisfactory therapeutic effects or reverse the progression of the disease. Calcineurin has been implicated as part of a critical signaling pathway for learning and memory, and neuronal calcineurin may be hyperactivated in AD. To investigate the effects and underlying mechanisms of FK506, a calcineurin inhibitor, on Alzheimer-like behavior and synaptic dysfunction in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease, we investigated the effect of FK506 on cognitive function and synaptic plasticity in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease. The results showed that FK506 treatment ameliorated cognitive deficits, as indicated by the decreased latency in the water maze, and attenuated tau hyperphosphorylation in 3 × Tg-AD mice. Treatment with FK506 also reduced the levels of certain markers of postsynaptic deficits, including PSD-95 and NR2B, and reversed the long-term potentiation deficiency and dendritic spine impairments in 3 × Tg-AD mice. These findings suggest that treatment with calcineurin inhibitors such as FK506 can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial Alzheimer's disease and related tauopathies.

Learning curve in relation to health-related quality of life in long-term, disease free survivors after McKeown minimally invasive esophagectomy.

BACKGROUND: The potential impact of learning curve on long-term health-related quality of life (QoL) after esophagectomy for cancer has not been investigated. The aim of this article is to investigate the relationship between learning curve for McKeown minimally invasive esophagectomy (MIE) and health-related quality of life (QoL) in long-term, disease free survivors up to 10 years after esophageal cancer resection. METHODS: Esophageal cancer patients who underwent McKeown MIE between 2009 and 2019 were identified in which 280 who were free of disease at the time of survey and completed health-related QoL and symptom questionnaires, including EORTC QLQ-C30, EORTC QLQ-OES18, and Digestive Symptom Questionnaire. Patients were assessed in 3 cohorts according to the learning phases of expertise reported by our previous study: initial phase; plateau phase, and; experienced phase. RESULTS: Median time from operation to survey was 5.8 years (interquartile range 4.6-8.2). The QLQ-C30 mean scores of functional scales, and symptom scales of respiratory and digestive systems including dyspnea (P = 0.006), shortness of breath (P = 0.003), and dysphagia (P = 0.031) were significantly better in experienced phase group. Furthermore, in the subgroup analyses for patients without postoperative major complications, patients in the initial learning phase remained suffering from more symptoms of dyspnea (P = 0.040) and shortness of breath (P = 0.001). CONCLUSION: Esophageal cancer patients undergoing McKeown MIE in initial learning phase tend to suffer from a deterioration in long-term health-related QoL and higher symptomatic burden as compared to experienced learning phase, which did not improved over time and warranted more attention.

Correlation of Blood and Intestinal Mucosa miR-34a Expressions with Disease Severity in Ulcerative Colitis Patients.

BACKGROUND: miR-34a has been implicated in many autoimmune diseases and gastrointestinal diseases. However, the expression of miR-34 in ulcerative colitis (UC) patients were not fully studied. This study was performed to in-vestigate the association of blood and intestinal tissue miR-34a expression of patients with disease severity in UC patients. METHODS: Our study enrolled 82 patients with UC and 80 age- and gender- matched healthy individuals. Blood miR-34a expressions were detected using reverse transcription-polymerase chain reaction (RT-PCR). Local intestinal miR-34a, STAT3 mRNA and IL-23 mRNA expressions were also detected in the lesioned area and adjacent non-affected intestinal tissue in patients. Disease severity of UC was assessed by Mayo score. The diagnostic value of both blood and local miR-34a expression for UC patients was assessed by receiver operating characteristic (ROC) curve. RESULTS: Blood miR-34a was increased in UC patients in contrast with healthy individuals with statistical significance. In UC patients, local intestinal miR-34a expressions were markedly upregulated compared to adjacent non-affected intestinal tissue. Local intestinal miR-34a expressions were positively correlated with STAT3 mRNA and IL-23 mNRA. Both blood and local miR-34a expressions were significantly and positively related to Mayo scores. ROC curve analysis indicated that both blood and local miR-34a expressions may act as decent marker for Mayo grade. CONCLUSIONS: Blood and intestinal tissue miR-34a expressions are correlated with disease severity in UC patients. Both blood and intestinal tissue miR-34a expressions may serve as potential diagnostic and prognostic makers for UC. Therapeutic methods targeting miR-34a may act as potential ways for UC treatment.

Systematic review and meta-analysis of the diagnostic value of computed tomography angiography for severe internal carotid artery stenosis.

BACKGROUND: Due to the increasing incidence of ischaemic cerebrovascular diseases, the accurate assessment of internal carotid artery (ICA) stenosis is crucial for the development of treatment plans. This systematic review and meta-analysis aimed to evaluate the diagnostic value of computed tomography angiography (CTA) for severe ICAstenosis, thereby providing support for clinical decision-making and promoting diagnostic updates. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical Literature (CBM) electronic databases were searched from inception to March 21, 2024, to identify publicly available research literature on the use of CTA to diagnose severe ICA stenosis. Literature screening, data extraction, and quality assessment were conducted based on the inclusion and exclusion criteria as well as the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) standards. Data analysis was performed using Stata 17.0 and Meta-Disc 1.4 software. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of the included studies were calculated using Stata 17.0 software, and forest plots and summary receiver operating characteristic (SROC) curves were generated. The area under the curve (AUC) was calculated, and funnel plots were constructed to assess publication bias. RESULTS: A total of 16 studies with 2368 vascular segments were included. The meta-analysis revealed that the combined sensitivity and specificity of CTA for severe ICA stenosis were 0.93 (95% CI: 0.88 ~ 0.96) and 0.99 (95% CI: 0.96 ~ 1.00), respectively. The combined positive likelihood ratio and negative likelihood ratio were 92.0 (95% CI: 24.2 ~ 349.6) and 0.07 (95% CI: 0.04 ~ 0.13), respectively. The diagnostic odds ratio was 1302 (95% CI: 257 ~ 6606), and the AUC of the SROC curve was 0.98. The Deeks funnel plot suggested no publication bias among the included studies. CONCLUSION: CTA demonstrated high sensitivity and specificity for diagnosing severe ICA stenosis. Therefore, this study provided important evidence for the accurate diagnosis and treatment of severe ICA stenosis. However, there was considerable heterogeneity among the included studies, thus indicating the need for additional high-quality prospective studies to confirm the clinical applicability of CTA.

Base excision repair system targeting DNA adducts of trioxacarcin/LL-D49194 antibiotics for self-resistance.

Two families of DNA glycosylases (YtkR2/AlkD, AlkZ/YcaQ) have been found to remove bulky and crosslinking DNA adducts produced by bacterial natural products. Whether DNA glycosylases eliminate other types of damage formed by structurally diverse antibiotics is unknown. Here, we identify four DNA glycosylases-TxnU2, TxnU4, LldU1 and LldU5-important for biosynthesis of the aromatic polyketide antibiotics trioxacarcin A (TXNA) and LL-D49194 (LLD), and show that the enzymes provide self-resistance to the producing strains by excising the intercalated guanine adducts of TXNA and LLD. These enzymes are highly specific for TXNA/LLD-DNA lesions and have no activity toward other, less stable alkylguanines as previously described for YtkR2/AlkD and AlkZ/YcaQ. Similarly, TXNA-DNA adducts are not excised by other alkylpurine DNA glycosylases. TxnU4 and LldU1 possess unique active site motifs that provide an explanation for their tight substrate specificity. Moreover, we show that abasic (AP) sites generated from TxnU4 excision of intercalated TXNA-DNA adducts are incised by AP endonuclease less efficiently than those formed by 7mG excision. This work characterizes a distinct class of DNA glycosylase acting on intercalated DNA adducts and furthers our understanding of specific DNA repair self-resistance activities within antibiotic producers of structurally diverse, highly functionalized DNA damaging agents.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

[Overview of new approaches to ß-thalassemia treatment].

Hemoglobinopathies are one of the most common single-gene genetic disorders globally, with approximately 1% to 5% of the global population carrying the mutated gene for thalassemia. Thalassemia are classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia based on the need for blood transfusion. Traditional treatment modalities include blood transfusion, splenectomy, hydroxyurea therapy, and iron chelation therapy, which are now widely used for clinical treatment and constitute the main methods recommended in the ß-thalassemia treatment guidelines. However, there are multiple barriers and limitations to the application of these approaches, and there is an urgent need to explore new therapeutic approaches. With the in-depth study of the pathophysiological process of ß-thalassemia, a deeper understanding of the pathogenesis of the disease has been gained. It has been demonstrated that the pathogenesis of thalassemia is closely related to ineffective erythropoiesis (IE), imbalance in the ratio of α/ß-globin protein chains and iron overload. New therapeutic approaches are emerging for different pathogenic mechanisms. Among them, new drugs for the treatment of IE mainly include activin receptor II trap ligands, Janus kinase 2 inhibitors, pyruvate kinase activators, and glycine transporter protein 1 inhibitors. Correcting the imbalance in the hemoglobin chain is mainly due to emerging technologies such as bone marrow transplantation and gene editing. Measures in reducing iron overload are associated with inhibiting the activity of transferrin and hepcidin. These new approaches provide new ideas and options for the treatment and management of ß-thalassemia.

Polyploidy in development and tumor models in Drosophila.

Polyploidy, a cell status defined as more than two sets of genomic DNA, is a conserved strategy across species that can increase cell size and biosynthetic production, but the functional aspects of polyploidy are nuanced and vary across cell types. Throughout Drosophila developmental stages (embryo, larva, pupa and adult), polyploid cells are present in numerous organs and help orchestrate development while contributing to normal growth, well-being and homeostasis of the organism. Conversely, increasing evidence has shown that polyploid cells are prevalent in Drosophila tumors and play important roles in tumor growth and invasiveness. Here, we summarize the genes and pathways involved in polyploidy during normal and tumorigenic development, the mechanisms underlying polyploidization, and the functional aspects of polyploidy in development, homeostasis and tumorigenesis in the Drosophila model.

Safety and Clinical Activity of SHR7390 Monotherapy or Combined With Camrelizumab for Advanced Solid Tumor: Results From Two Phase I Trials.

BACKGROUND: SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD). A recommended dose for expansion was determined based on the safety and tolerability of the dose-escalation stage. The primary endpoints were dose limiting toxicity (DLT) and MTD. RESULTS: In the SHR7390 monotherapy trial, 16 patients were enrolled. DLTs were reported in the 1.0 mg cohort, and the MTD was 0.75 mg. Grade ≥3 treatment-related adverse events (TRAEs) were recorded in 4 patients (25.0%). No patients achieved objective response. In the SHR7390 combination trial, 22 patients with CRC were enrolled. One DLT was reported in the 0.5 mg cohort and the MTD was not reached. Grade ≥3 TRAEs were observed in 8 patients (36.4%), with the most common being rash (n=4). One grade 5 TRAE (increased intracranial pressure) occurred. Five patients (22.7%) achieved partial response, including one of 3 patients with MSS/MSI-L and BRAF mutant tumors, one of 15 patients with MSS/MSI-L and BRAF wild type tumors, and all 3 patients with MSI-H tumors. CONCLUSIONS: SHR7390 0.5 mg plus camrelizumab showed a manageable safety profile. Preliminary clinical activity was reported regardless of MSI and BRAF status.

Impact of perioperative decreased serum albumin level on anastomotic leakage in esophageal squamous cell carcinoma patients treated with neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a severe complication following esophagectomy with high mortality. Perioperative decreased serum albumin level is considered a predictive of AL, however, its impact on AL incidence in patients treated with neoadjuvant chemotherapy (NCT) followed by minimally invasive esophagectomy (MIE) is not well defined. METHODS: The data of 318 consecutive esophageal cancer patients who underwent MIE were collected retrospectively from January 2021 to December 2021. The perioperative level of albumin was detected and the baseline of altering levels for albumin was established. The incidence of postoperative complications and survival rate were analyzed between groups. RESULTS: After exclusion, 137 patients were enrolled and assigned to more decreased albumin (MA) and less decreased albumin (LA) groups. The levels of albumin descended significantly after MIE (p < 0.0001). There was no significant difference in the clinicopathologic characteristics or surgical outcomes between groups. The incidence of postoperative AL was 10.2% in MA group and 1.4% in LA group (p = 0.033). Three patients died due to AL in MA group, while no mortality was observed in LA group (p = 0.120). The rate of other postoperative complications was similar between groups. Progression-free survival (PFS) in LA group was a little higher than that in MA group, but it was no significant difference (p = 0.853). Similarly, no difference was observed in overall survival (OS) between groups (p = 0.277). CONCLUSIONS: Severely deficient serum albumin after MIE was an indicator of AL in esophageal cancer patients treated with NCT. TRIAL REGISTRATION: Chinese clinical trial registry: ChiCTR2200066694, registered December14th,2022. https://www.chictr.org.cn/edit.aspx?pid=185067&htm=4 .

A single-cell atlas of adult Drosophila ovary identifies transcriptional programs and somatic cell lineage regulating oogenesis.

Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modeled extensively using the Drosophila ovary. Although different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic data set for the adult Drosophila ovary and connected tissues. Using this data set, we identified the transcriptional trajectory of the entire follicle-cell population over the course of their development from stem cells to the oogenesis-to-ovulation transition. We further identify expression patterns during essential developmental events that take place in somatic and germline cell types such as differentiation, cell-cycle switching, migration, symmetry breaking, nurse-cell engulfment, egg-shell formation, and corpus luteum signaling. Extensive experimental validation of unique expression patterns in both ovarian and nearby, nonovarian cells also led to the identification of many new cell type-and stage-specific markers. The inclusion of several nearby tissue types in this data set also led to our identification of functional convergence in expression between distantly related cell types such as the immune-related genes that were similarly expressed in immune cells (hemocytes) and ovarian somatic cells (stretched cells) during their brief phagocytic role in nurse-cell engulfment. Taken together, these findings provide new insight into the temporal regulation of genes in a cell-type specific manner during oogenesis and begin to reveal the relatedness in expression between cell and tissues types.

Streptomonospora mangrovi sp. nov., isolated from mangrove soil showing similar metabolic capabilities, but distinct secondary metabolites profiles.

A novel actinomycete, designated strain S1-112 T, was isolated from a mangrove soil sample from Hainan, China, and characterized using a polyphasic approach. Strain S1-112 T showed the highest similarity of the 16S rRNA gene to Streptomonospora nanhaiensis 12A09T (99.24%). Their close relationship was further supported by phylogenetic analyses, which placed these two strains within a stable clade. The highest values of digital DNA-DNA hybridization (dDDH, 41.4%) and average nucleotide identity (ANI, 90.55%) were detected between strain S1-112 T and Streptomonospora halotolerans NEAU-Jh2-17 T. Genotypic and phenotypic characteristics demonstrated that strain S1-112 T could be distinguished from its closely related relatives. We also profiled the pan-genome and metabolic features of genomic assemblies of strains belonging to the genus Streptomonospora, indicating similar functional capacities and metabolic activities. However, all of these strains showed promising potential for producing diverse types of secondary metabolites. In conclusion, strain S1-112 T represents a novel species of the genus Streptomonospora, for which the name Streptomonospora mangrovi sp. nov. was proposed. The type strain is S1-112 T (= JCM 34292 T).

Concurrent radiotherapy cannot provide superiority of surgical oncological outcome and long-term survival rate in locally advanced esophageal squamous cell carcinoma patients receiving neoadjuvant chemotherapy followed by minimally invasive esophagectomy.

BACKGROUND: To evaluate effectiveness of concurrent radiotherapy in esophageal cancer patient treated with neoadjuvant therapy. METHODS: The data of 1026 consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent minimally invasive esophagectomy (MIE) were retrospectively collected. The main inclusion criteria were patients with locally advanced (cT2-4N0-3M0) ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) or neoadjuvant chemotherapy (NCT) followed by MIE, and divided into two groups according to different neoadjuvant strategies. Propensity score matching was performed to improve the comparability between the two groups. RESULTS: After exclusion and matching, 141 patients were enrolled retrospectively: 92 received NCT, and 49 received NCRT. No difference in clinicopathologic characteristics or incidence of adverse events between groups. A shorter operation time (215.7 ± 35.5 min) (p < 0.001), less blood loss (111.2 ± 67.7 ml) (p = 0.0007) and a greater number of lymph nodes retrieved (33.8 ± 11.7) (p = 0.002) were observed in NCT group than in NCRT group. The incidence of postoperative complications was similar between groups. Although patients in NCRT group had better pathological complete response (16, 32.7%) (p = 0.0026) and ypT0N0 (10, 20.4%) (p = 0.0002) rates, there was no significant difference in 5-year progression-free survival (p = 0.1378) or disease-specific survival (p = 0.1258) between groups. CONCLUSIONS: Compared with NCRT, NCT has certain advantages in that it can simplify the surgical procedure and decrease the surgical technique required without compromising the surgical oncological outcomes and long-term survival of patients.

Safety and feasibility of three-dimensional McKeown minimally invasive esophagectomy.

BACKGROUND: To compare the perioperative outcomes from McKeown minimally invasive esophagectomy (MIE) when performed in three-dimensional versus two-dimensional visualization system, and investigate the learning curve of a single surgeon who implemented three-dimensional McKeown MIE. METHODS: A total of 335 consecutive cases (three-dimensional or two-dimensional) were identified. Perioperative clinical parameters were compared and cumulative sum learning curve was plotted. Propensity score matching was used to reduce selection bias from confounding factors. RESULTS: Patients in three-dimensional group were associated with more chronic obstructive pulmonary disease (23.9% vs 3.0%, p < 0.01). After propensity score matching (108 matched patients in each groups), this finding was no longer statistically significant. Comparing to two-dimensional group, significant improvement in total retrieved lymph nodes (28 vs 33, p = 0.003) was observed in three-dimensional group. In addition, more lymph nodes around the right recurrent laryngeal nerve were harvested in three-dimensional group than that in two-dimensional group (p = 0.045). However, there were no significantly differences were found between the two groups in terms of other intraoperative parameters (e.g., operative time) and postoperative relevant outcomes (e.g., lung infection). Furthermore, the change point in the cumulative sum learning curves for intraoperative blood loss and thoracic procedure time was 33 procedures, respectively. CONCLUSION: Three-dimensional visualization system appears to be superior in performing lymphadenectomy during McKeown MIE to that of a two-dimensional technique. For surgeons proficient in performing two-dimensional McKeown MIE, the learning curve for a three-dimensional procedure appears to begin near proficiency after more than 33 cases.

A novel 22-bp InDel within FGF7 gene is significantly associated with growth traits in goat.

Fibroblast growth factor 7 (FGF7) is involved in lipid metabolism, which is considered as a candidate gene with close relation with muscle development by eGWAs and RNA-Seq analyses. To date, limited research has been conducted on the relationship between FGF7 gene and growth traits. The main objective of this work was to further investigate the association between novel InDel within FGF7 gene and growth traits in goat. Herein, FGF7 mRNA expression levels were investigated in various Fuqing goat tissues. We found that FGF7 gene was expressed in six adult goat tissues with the highest mRNA levels in adipose tissue. This result suggested that FGF7 gene might play a critical role in fat deposition. We also detected potential polymorphisms in Fuqing, Nubian and Jianyang Daer breeds. A 22-bp InDel polymorphism in FGF7 gene was detected in 396 goats and the three genotypes were designated as II, ID, and DD. Correlation analysis revealed that InDel polymorphism was significantly associated with growth traits (P < 0.05). Goats with genotypes ID and/or II had superior growth traits compared to those with genotype DD. In summary, our findings suggested that the 22-bp InDel within FGF7 gene could act as a molecular marker to improve the growth traits of goats in breeding programs.

A novel splice variant of goat CPT1a gene and their diverse mRNA expression profiles.

The Alternative splicing (AS) of Carnitine palmitoyltransferase 1a (CPT1a) and their expression profiles had never been illuminated in goats until now. Herein, a novel splice transcript in the CPT1a gene that is predicted to result in the skipping of exons 6-19 (CPT1a-sv1) has been isolated in addition to the full-length transcript in goats. The result of RT-PCR showed that CPT1a-sv1 is 606 bp in length and consists of 6 exons. A novel exon 6 was consisted of partial exon 5 and partial exon 19, compared to that in CPT1a. RT-qPCR analysis showed that the expression patterns of CPT1a and CPT1a-sv1 are spatially different. In both kid and adult goats, the CPT1a transcript is strongly expressed in the liver, spleen, lung, kidney, and brain tissues. However, CPT1a-sv1 has a strong tissue-specific expression pattern, with moderate RNA levels in the liver and brain of kids, while highly expressed in the liver and minimally expressed in the brain of adults. We observed two transcripts to be involved in brain development. These findings improve our understanding of the function of the CPT1a gene in goats and provide information on the molecular mechanism of AS events.

A Predictive Model for Chronic Hydrocephalus After Clipping Aneurysmal Subarachnoid Hemorrhage.

Chronic hydrocephalus after clipping aneurysmal subarachnoid hemorrhage (aSAH) often results in poor outcomes. This study was to establish and validate model to predict chronic hydrocephalus after aSAH by least absolute shrinkage and selection operator logistic regression. The model was constructed from a retrospectively analyzed. Two hundred forty-eight patients of aSAH were analyzed retrospectively in our hospital from January 2019 to December 2021, and the patients were divided into chronic hydrocephalus (CH) group (n=55) and non-CH group (n=193) according to whether occurred CH within 3 months. In summary, 16 candidate risk factors related to chronic hydrocephalus after aSAH were analyzed. Univariate analysis was performed to judging the risk factors for CH. The least absolute shrinkage and selection operator regression was used to filter risk factors. Subsequently, the nomogram was designed by the above variables. And area under the curve and calibration chart were used to detect the discrimination and goodness of fit of the nomogram, respectively. Finally, decision curve analysis was constructed to assess the practicability of the risk of chronic hydrocephalus by calculating the net benefits. Univariate analysis showed that age (60 y or older), aneurysm location, modified Fisher grade, Hunt-Hess grade, and the method for cerebrospinal fluid drainage, intracranial infections, and decompressive craniectomy were significantly related to CH ( P <0.05). Whereas 5 variables [age (60 y or older), posterior aneurysm, modified Fisher grade, Hunt-Hess grade, decompression craniectomy] from 16 candidate factors were filtered by LASSO logistic regression for further research. Area under the curve of this model was 0.892 (95% confidence interval: 0.799-0.981), indicating a good discrimination ability. Meanwhile, the result of calibration indicated a good fitting between the prediction probability and the actual probability. Finally, decision curve analysis showed a good clinical efficacy. In summary, this model could conveniently predict the occurrence of chronic hydrocephalus after aSAH. Meanwhile, it could help physicians to develop personalized treatment and close follow-up for these patients.

An Efficient CRT Based Algorithm for Frequency Determination from Undersampled Real Waveform.

The Chinese Remainder Theorem (CRT) based frequency estimation has been widely studied during the past two decades. It enables one to estimate frequencies by sub-Nyquist sampling rates, which reduces the cost of hardware in a sensor network. Several studies have been done on the complex waveform; however, few works studied its applications in the real waveform case. Different from the complex waveform, existing CRT methods cannot be straightforwardly applied to handle a real waveform's spectrum due to the spurious peaks. To tackle the ambiguity problem, in this paper, we propose the first polynomial-time closed-form Robust CRT (RCRT) for the single-tone real waveform, which can be considered as a special case of RCRT for arbitrary two numbers. The time complexity of the proposed algorithm is O(L), where L is the number of samplers. Furthermore, our algorithm also matches the optimal error-tolerance bound.