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Abstract Background or Purpose A practical noninvasive method to identify sentinel lymph node (SLN) status in breast cancer patients, who had a suspicious axillary lymph node (ALN) at ultrasound (US), but a negative clinical physical examination is needed. To predict SLN metastasis using a nomogram based on US and biopsy‐based pathological features, this retrospective study investigated associations between clinicopathological features and SLN status. Methods Patients treated with SLN dissection at four centers were apportioned to training, internal, or external validation sets (n = 472, 175, and 81). Lymph node ultrasound and pathological characteristics were compared using chi‐squared and t‐tests. A nomogram predicting SLN metastasis was constructed using multivariate logistic regression models. Results In the training set, statistically significant factors associated with SLN+ were as follows: histology type (p

Abstract Background Few studies have investigated the change in life expectancy (LE) and the healthy lifespan among patients with advanced schistosomiasis. This study was to evaluate the LE and healthy life expectancy (HLE) for patients and assess the mechanism responsible for the LE inequality. Methods We utilized data from a dynamic advanced schistosomiasis cohort (10,362 patients) for the period from January 2008 to December 2019 in Hunan Province, China, to calculate the LEs of patients, and made a comparison with that of general population (19,642 schistosomiasis-free individuals) in the schistosomiasis endemic areas. LEs were estimated from 15 years of age by constructing period life tables. Arriaga’s decomposition method was applied to quantify the influence of the age structure on the difference in LE. HLE for advanced schistosomiasis patients was calculated by using Sullivan method with age-specific disability weight. The LE and HLE were calculated for both males and females to perform further analyses on gender gap. Results The estimated LE for advanced schistosomiasis patients aged 15–19 was 49.51 years (48.86 years for males and 51.07 years for females), which was 20.14 years lower compared with general population (69.65 years), and the LE gap between patients and general population decreased with age. The largest age-specific mortality contribution to the gap (32.06%) occurred at age 80–84 years. Women had a lower LE and HLE than men at age ≥ 60 years (both gender gaps in LE and HLE

Abstract Background The results of halo sign in the differential diagnosis of thyroid nodules were conflicting, and the value of contrast-enhanced ultrasound (CEUS) in characterization of thyroid nodules with halo has not been fully evaluated. This study was therefore designed to investigate the value of contrast-enhanced ultrasound features in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound. Material and methods Seventy-four consecutive thyroid nodules with halo sign on B-mode ultrasound were pathologically confirmed by surgery or fine needle aspiration, including 43 benign and 31 malignant lesions. All these lesions underwent pre-operative CEUS examination. The CEUS features, including enhanced time, enhanced intensity and homogeneity, and presence of enhancing ring, were compared between benign and malignant ones. Results Enhanced intensity was significant different between benign and malignant lesions with halo. Hypo-enhancement was more frequently detected in malignant nodules than that in benign ones, compared with iso-enhancement and hyper-enhancement (p = 0.013, and = 0.014, respectively). Detection rate of high-enhancing ring was significantly higher in benign nodules than that in malignant group (p = 0.001). While in nodules > 10 mm, only high-enhancing ring was the distinguishing feature between benign and malignant nodules. Conclusions Enhanced intensity and high-enhancing ring may be helpful in the differential diagnosis of thyroid nodules with halo sign on B-mode ultrasound.

Abstract Tumor-associated macrophages (TAMs) account for 30–50% of glioma microenvironment. The interaction between glioma tumor cells and TAMs can promote tumor progression, but the intrinsic mechanisms remain unclear. Herein, we reported that soluble LRIG3 (sLRIG3) derived from glioma tumor cells can block the M2 polarization of TAMs via interacting with NETO2, thus suppressing GBM malignant progression. The expression or activity of ADAM17 in glioma cells was positively correlated with the expression of sLRIG3 in cell supernatant. Soluble LRIG3 can suppress the M2-like polarity transformation of TAMs and inhibit the growth of tumor. High expression of LRIG3 predicts a good prognosis in patients with glioma. Mass spectrometry and Co-immunoprecipitation showed that sLRIG3 interacts with the CUB1 domain of NETO2 in TAMs. Silencing or knockout of NETO2 could block the effect of sLRIG3, which inhibited the M2-like polarity transformation of TAMs and promoted GBM tumor growth. However, overexpressing His-target NETO2 with CUB1 deletion mutation does not fully recover the suppressive effects of sLRIG3 on the TAM M2-polarization in NETO2-Knockout TAMs. Our study revealed vital molecular crosstalk between GBM tumor cells and TAMs. Glioma cells mediated the M2 polarization of TAM through the sLRIG3-NETO2 pathway and inhibited the progression of GBM, suggesting that sLRIG3-NETO2 may be a potential target for GBM treatment.

With complicated pathogenesis and limited treatment options, optic neuropathy is one of the major blinding diseases characterized by damaged retinal ganglion cells(RGC)and axons. Sigma-1 receptor(S1R)is a chaperone protein mainly located in the endoplasmic reticulum membrane, which is abundant in retina and highly expressed in the ganglion cell layer. S1R has been noted increasingly as a novel target for the treatment of neuro-degenerations. More studies have shown that S1R is a pluripotent modulator including Ca2+ homeostasis, endoplasmic reticulum stress response, oxidative stress response, neurotrophic factor secretion and glial cell activation, indicating that S1R can generate significant impacts on neuroprotection in neurodegenerative diseases. Additionally, S1R also has neuroprotective effects against RGC loss and dysfunction both in vivo and in vitro, reversing loss partially and maintaining structural integrity, while the absence of S1R exacerbates the disease or increases vulnerability to degenerative diseases. This article intends to review the progress and mechanisms in neuroprotection of S1R in RGC, aiming to provide a new target for the treatment of optic neuropathy.

BackgroundElderly patients with breast cancer are highly heterogeneous, and tumor load and comorbidities affect patient prognosis. Prediction models can help clinicians to implement tailored treatment plans for elderly patients with breast cancer. This study aimed to establish a prediction model for breast cancer, including comorbidities and tumor characteristics, in elderly patients with breast cancer.MethodsAll patients were ≥65 years old and admitted to the Peking Union Medical College Hospital. The clinical and pathological characteristics, recurrence, and death were observed. Overall survival (OS) was analyzed using the Kaplan–Meier curve and a prediction model was constructed using Cox proportional hazards model regression. The discriminative ability and calibration of the nomograms for predicting OS were tested using concordance (C)-statistics and calibration plots. Clinical utility was demonstrated using decision curve analysis (DCA).ResultsBased on 2,231 patients, the 5- and 10-year OS was 91.3% and 78.4%, respectively. We constructed an OS prediction nomogram for elderly patients with early breast cancer (PEEBC). The C-index for OS in PEEBC in the training and validation cohorts was 0.798 and 0.793, respectively. Calibration of the nomogram revealed a good predictive capability, as indicated by the calibration plot. DCA demonstrated that our model is clinically useful.ConclusionThe nomogram accurately predicted the 3-year, 5-year, and 10-year OS in elderly patients with early breast cancer.

A new study considering data from 7603 households across 28 sites in 22 low- and middle-income countries show that inequality of household water security follows a Development Kuznets Curve.

Abstract Lumbar disc herniation (LDH) can be spontaneously absorbed without surgical treatment. However, the pathogenesis and physiological indications for predicting protrusion reabsorption are still unclear, which prevents clinicians from preferentially choosing conservative treatment options for LDH patients with reabsorption effects. The purpose of this review was to summarize previous reports on LDH reabsorption and to discuss the clinical and imaging features that favor natural absorption. We highlighted the biological mechanisms involved in the phenomenon of LDH reabsorption, including macrophage infiltration, inflammatory responses, matrix remodeling, and neovascularization. In addition, we summarized and discussed potential clinical treatments for promoting reabsorption. Current evidence suggests that macrophage regulation of inflammatory mediators, matrix metalloproteinases, and specific cytokines in intervertebral disc is essential for the spontaneous reabsorption of LDH.

A high-quality genome assembly for the lilac (Syringa oblata) provides insight into the evolution of this shrub and potential mechanisms underlying petal color change.

Abstract Cerebellar ataxias are characterized by a progressive decline in motor coordination, but the specific output circuits and underlying pathological mechanism remain poorly understood. Through cell-type-specific manipulations, we discovered a novel GABAergic Purkinje cell (PC) circuit in the cerebellar IV/V lobe that projected to CaMKIIα+ neurons in the fastigial nucleus (FN), which regulated sensorimotor coordination. Furthermore, transcriptomics profiling analysis revealed various cerebellar neuronal identities, and we validated that biorientation defective 1 (BOD1) played an important role in the circuit of IV/V lobe to FN. BOD1 deficit in PCs of IV/V lobe attenuated the excitability and spine density of PCs, accompany with ataxia behaviors. Instead, BOD1 enrichment in PCs of IV/V lobe reversed the hyperexcitability of CaMKIIα+ neurons in the FN and ameliorated ataxia behaviors in L7-Cre; BOD1 f/f mice. Together, these findings further suggest that specific regulation of the cerebellar IV/V lobePCs → FNCaMKIIα+ circuit might provide neuromodulatory targets for the treatment of ataxia behaviors.

Background: Breast cancer is the most common malignancy in women. Clinical models such as Oncotype DX recurrence score (RS) and Clinical Treatment Score post–5 years (CTS5) model for survival prediction are crucial for clinical practice. However, it remains unclear whether CTS5 or RS would be a more powerful clinical model for recurrence risk evaluation. Therefore, we conducted the present study to compare the performance of CTS5 risk model and RS on different recurrence evaluation. And we further integrated the two models into a novel nomogram to improve the power for prognosis prediction. Methods: Female patients with invasive hormone receptor positive breast cancer in the Surveillance, Epidemiology, and End Results Program (SEER) database with RS data available were included. The clinicopathological data were directly extracted from SEER database. Participants were divided into three subsets according to recurrence timing (60 months) for model evaluation. Survival receiver operating characteristic curve and C-index were calculated to evaluate discrimination. Calibration curve were used to visual inspection for calibration. Model comparison was assessed by net reclassification index (NRI) method. Nomogram prognostic model was developed with the combination of CTS5 score and RS and also included other critical clinicopathological parameters. Results: In total, 64044 breast cancer patients were enrolled for analysis. The number of patients with survival 60 months (late recurrence subset) were 64044, 36878 and 15926, respectively. For model discrimination, CTS5 model was superior to RS for overall survival (OS) prediction (likelihood ratio test P

Monte Carlo simulations show that, as temperature increases, the average kinetic energy of channel electrons in a GaN transistor first decreases and then increases. According to the calculations, the relative energy change reaches 40%. This change leads to a reduced barrier height due to quantum coupling among the three-dimensional motions of channel electrons. Thus, an analysis and physical model of the gate leakage current that includes drift velocity is proposed. Numerical calculations show that the negative and positive temperature dependence of gate leakage currents decreases across the barrier as the field increases. They also demonstrate that source?drain voltage can have an effect of 1 to 2 orders of magnitude on the gate leakage current. The proposed model agrees well with the experimental results.

Abstract Background During the disease cycle, plant pathogenic fungi exhibit a morphological transition between hyphal growth (the phase of active infection) and the production of long-term survival structures that remain dormant during “overwintering.” Verticillium dahliae is a major plant pathogen that produces heavily melanized microsclerotia (MS) that survive in the soil for 14 or more years. These MS are multicellular structures produced during the necrotrophic phase of the disease cycle. Polyketide synthases (PKSs) are responsible for catalyzing production of many secondary metabolites including melanin. While MS contribute to long-term survival, hyphal growth is key for infection and virulence, but the signaling mechanisms by which the pathogen maintains hyphal growth are unclear. Results We analyzed the VdPKSs that contain at least one conserved domain potentially involved in secondary metabolism (SM), and screened the effect of VdPKS deletions in the virulent strain AT13. Among the five VdPKSs whose deletion affected virulence on cotton, we found that VdPKS9 acted epistatically to the VdPKS1-associated melanin pathway to promote hyphal growth. The decreased hyphal growth in VdPKS9 mutants was accompanied by the up-regulation of melanin biosynthesis and MS formation. Overexpression of VdPKS9 transformed melanized hyphal-type (MH-type) into the albinistic hyaline hyphal-type (AH-type), and VdPKS9 was upregulated in the AH-type population, which also exhibited higher virulence than the MH-type. Conclusions We show that VdPKS9 is a powerful negative regulator of both melanin biosynthesis and MS formation in V. dahliae. These findings provide insight into the mechanism of how plant pathogens promote their virulence by the maintenance of vegetative hyphal growth during infection and colonization of plant hosts, and may provide novel targets for the control of melanin-producing filamentous fungi.

Abstract Background Clonorchiasis, an infectious disease caused by the liver fluke Clonorchis sinensis, may lead to the development of liver and gallbladder diseases, and even cholangiocarcinoma (CCA). However, the pathogenesis, host-pathogen interaction, and diagnostic markers for clonorchiasis remain unclear. Methods Eighteen rabbits were randomly divided into control group (n = 9) and C. sinensis-infected group (n = 9), and their plasma samples were collected at 7, 14, 28, and 63 days post-infection (dpi). Biochemical indices and metabolites in different infection periods were detected. A non-targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was employed to investigate the metabolic profiles of plasma in rabbits, and related metabolic pathways of differential metabolites and correlation between candidate biochemical indices and differential metabolites were analyzed. Finally, the candidate biomarkers were verified with human samples using a targeted metabolomics method. Results The result of biochemical indices indicated C. sinensis infection would affect the liver function biochemical indices, especially alanine aminotransferase, aspartate transaminase (AST), glutamyl transpeptidase (GGT), total bile acid, high-density lipoprotein, and cholinesterase. The metabonomic results showed that 58, 212, 23, and 21 differential metabolites were identified in different phases of the infection. Multivariate statistical analysis of differential metabolites revealed distinct metabolic signatures during different phases of infection, with most of these signatures being observed at 14 dpi, which mainly influences the amino acid metabolisms. For metabolites and biochemical indices, AST, GGT, hypoxanthine, l-pipecolic acid, and d-glucuronate represented potential noninvasive biomarkers for the diagnosis of C. sinensis (P 0.8). Furthermore, GGT and d-glucuronate levels were positively correlated with the infection (r(28) = 0.98, P

With the development of science and technology, digital economy has penetrated into traditional manufacturing industry extensively and deeply, which has motivated the progress of the digital transformation for traditional manufacturing industry. Through comparative analysis of theoretical mechanism of synergetic development, this paper researches the order degree model and the synergy degree model based on the social shaping of technology theory to evaluate the synergetic degree of the digital transformation for China's traditional manufacturing industry. An empirical study is presented based on the proposed models and the spatial analysis method by using the statistical data of Yangtze River Delta in China from 2014 to 2019. The results were consistent with the actual situation and indicated that the model fully reflect the dynamic interaction between systems, which is a sound basis for scientific judgment and effective decision-making when seeking to the digital transformation of traditional manufacturing industry.

Tetrameres grusi is a significant parasitic nematode of cranes that is classified into suborder Spirurina. However, for more than a century, this classification has been controversial. Mitochondrial genomes are valuable resources for parasite taxonomy, population genetics and systematics studies. Here, the mitochondrial genome of T. grusi was determined and subsequently compared with those from Spirurina species using concatenated datasets of amino acid sequences predicted from mitochondrial protein-coding genes. The complete mitochondrial genome of T. grusi is circular with 13,709 bp, and it contains 12 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and one non-coding region. All of the protein-coding genes are transcribed in the same direction. There were 18 intergenic spacers of 1–44 bp, and six locations with gene overlaps, ranging from 1 bp to 28 bp, in the mitochondrial genome of T. grusi. The AT content of this mitochondrial genome was 71.56%. This was similar to mitochondrial genomes of other Spirurina species, which also exhibited strong AT content bias, not only in the nucleotide composition but also in codon usage. The sequenced mitogenomes of the 25 Spirurina nematodes showed three classes of gene arrangements based on the 12 protein-coding genes, and the gene arrangement of the T. grusi mitochondrial genome belonged to the Class I. Phylogenetic analyses using mitochondrial genomes of 25 Spirurina nematodes revealed that T. grusi (Habronematoidea) was closer to Gongylonema pulchrum (Spiruroidea) than Spirocerca lupi (Thelazioidea). The availability of the complete mitochondrial genome sequence of T. grusi provides new and useful genetic markers for further studies on Spirurina nematodes.

Constructing highly efficient catalysts for the degradation of organic pollutants driven by solar light in aquatic environments is a promising and green strategy. In this study, a novel hexagonal sheet-like Pt/SnS2 heterojunction photocatalyst is successfully designed and fabricated using a hydrothermal method and photodeposition process for photocatalytic tetracycline (TC) degradation. The optimal Pt/SnS2 hybrid behaves with excellent photocatalytic performance, with a degradation efficiency of 91.27% after 120 min, a reaction rate constant of 0.0187 min−1, and durability, which can be attributed to (i) the formation of a metal/semiconductor interface field caused by loading Pt nanoparticles (NPs) on the surface of SnS2, facilitating the separation of photo-induced charge carriers; (ii) the local surface plasmon resonance (LSPR) effect of Pt NPs, extending the light absorption range; and (iii) the sheet-like structure of SnS2, which can shorten the transmission distance of charge carriers, thereby allowing more electrons (e−) and holes (h+) to transfer to the surface of the catalyst. This work provides new insights with the utilization of sheet-like structured materials for highly active photocatalytic TC degradation in wastewater treatment and environmental remediation. [ABSTRACT FROM AUTHOR]

Abstract Background The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. Methods This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1–7, then 4 mg bid on days 8–21) or the first 2 cycles (4 mg tid on days 1–7, then 4 mg bid on days 8–42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. Discussion This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. Trial registration ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

Abstract Osteoarthritis (OA) is a chronic degenerative joint disease associated with age, mechanical stress, and obesity. Echinacea purpurea is a medicinal plant that shows good anti-inflammatory, antioxidant, and immunomodulatory activities. In this study, Echinacea purpurea ethanol extract nanoparticles (Nano-EE) were prepared by encapsulating Echinacea purpurea ethanol extract (EE) in chitosan-silica nanoparticles. Obesity (OB) in Sprague-Dawley (SD) rats was induced by fed 40% high-fat diet and then anterior cruciate ligament and meniscus injury were performed to induce OA. The rats got different doses of samples by oral gavage. The encapsulation efficiency and loading capacity of Nano-EE were 69.1% and 36.1%, respectively. The average size, polydispersity index (PDI), and zeta potential (ZP) of the Nano-EE were 145 ± 11 nm, 0.24 ± 0.01, − 4.57 ± 0.44 mV, respectively. Furthermore, electron microscopic images showed that the particles were spherical and were slightly agglomerated. Moreover, it showed that the leptin content, expression of MMPs, cytokines level, NF-κB level, and iNOS production were decreased whereas collagen II expression was increased after treatment. Besides, Nano-EE ameliorated the pain caused by OA and reduced the proteoglycan loss in cartilage. These results indicated that encapsulated EE (Nano-EE) can ameliorate OA with a low dosage and are more effective than unencapsulated EE.

The sub-micron bimodal grain structure of 301 austenitic stainless steel stripe obtained by phase reversion process, and the relationship between grain size distribution and mechanical properties was described in this study. With the change of annealing heating rate under the industrial condition 10 °C/min, the bimodal grain size of submicron scale was obtained at 750 °C. By analyzing the micrograph of bimodal structure, it was found that the deformed martensite transformed to austenite through diffusion transformation, and the recovery austenite grain had obvious size distribution. It was found that the bimodal structure was easier to form under the condition of slow heating rate, and the ultra-fine grain materials with high performance were obtained by controlling the annealing parameter. The high-density grain boundary of ultrafine grain presents microvoid in the tensile fracture, and the streaks formed by the aggregation of holes can be observed, which is considered to be caused by deformation twinning. The large dimples in the coarse grain are observed, as the strain-induced martensite was formed in the large grain of the bimodal structure.

Under the background of the long-term coexistence of the 4th and 5th Generation Mobile Communication Technology (4G and 5G), as the Segment Routing (SRv6) protocol standard based on the Internet Protocol version 6 (IPv6) forwarding plane is basically mature, SRv6 and Multi Protocol Label Switching (MPLS) interoperability and convergence in the mobile bearer network has been highlighted. This article discusses the methods on how to smoothly enable the interoperability and convergence of SRv6 and MPLS. It also proposes an efficient approach for all telecommunication operators to consult.

It is the basic characteristic of pure vortex light that there is a phase singularity at the origin. Such a singularity may be multiple degenerate, which determines the order of vortex light. Singularities splitting phenomenon means that singularities no longer concentrate at the origin but distribute around the space, usually occurring in impure vortex light. In this paper, we demonstrate the singularities splitting phenomenon and propose an analysis method, based on which one may rapidly estimate the modal components of impure vortex light. As two common singularity discrimination methods, the spiral and fork wire interference patterns are compared in distinguishing splitting singularities. The most widely used spiral interference pattern is revealed to be the worst form because of the low resolution. Instead, the fork wire interference pattern is with higher and easily adjusted resolution. 1‰ impurity is still able to be distinguished through fork wire interference patterns in the experiment.

Abstract Grain size is subtly regulated by multiple signaling pathways in rice. Alternative splicing is a general mechanism that regulates gene expression at the post-transcriptional level. However, to our knowledge, the molecular mechanism underlying grain size regulation by alternative splicing is largely unknown. GS3, the first identified QTL for grain size in rice, is regulated at the transcriptional and post-translational level. In this study, we identified that GS3 is subject to alternative splicing. GS3.1 and GS3.2, two dominant isoforms, accounts for about 50% and 40% of total transcripts, respectively. GS3.1 encodes the full-length protein, while GS3.2 generated a truncated proteins only containing OSR domain due to a 14 bp intronic sequence retention. Genetic analysis revealed that GS3.1 overexpressors decreased grain size, but GS3.2 showed no significant effect on grain size. Furthermore, we demonstrated that GS3.2 disrupts GS3.1 signaling by competitive occupation of RGB1. Therefore, we draw a conclusion that the alternative splicing of GS3 decreases the amount of GS3.1 and GS3.2 disrupts the GS3.1 signaling to inhibit the negative effects of GS3.1 to fine-tune grain size. Moreover, the mechanism is conserved in cereals rather than in Cruciferae, which is associated with its effects on grain size. The results provide a novel, conserved and important mechanism underlying grain size regulation at the post-transcriptional level in cereals.

BackgroundThe high relative mortality rate in elderly breast cancer patients is most likely the result of comorbidities rather than the tumor load. Foregoing axillary lymph node dissection or omitting radiotherapy after breast-conserving surgery (BCS) does not affect the prognosis of elderly breast cancer patients. We sought to assess the safety of breast-conserving surgery without axillary lymph node dissection as well as breast and axillary radiotherapy (BCSNR) in elderly patients with early-stage breast cancer.MethodsWe retrospectively included 541 consecutive breast cancer patients aged over 70 years with clinically negative axillary lymph nodes in one clinical center. Of these patients, 181 underwent mastectomy plus axillary lymph node dissection (MALND) with negative axillary cleaning and 360 underwent BCSNR.ResultsAfter a median follow-up of 5 years, there was no significant difference between the BCSNR and MALND groups in either distant recurrence-free survival (DRFS) (p=0.990) or breast cancer-specific survival (p=0.076). Ipsilateral axillary disease was found in 11 (3.1%) patients in the BCSNR group and 3 (1.7%) patients in the MALND group; this difference was not significant (p=0.334). We did not observe a significant difference in distant recurrence between the groups (p=0.574), with 25 (6.9%) patients in the BCSNR group experiencing distant recurrence compared to 15 (8.3%) patients in the MALND group. Our findings did show a significant difference in ipsilateral breast cancer recurrence (IBTR), with 31 (8.6%) patients in the BCSNR group experiencing IBTR compared to only 2 (1.1%) patients in the MALND group (p=0.003).ConclusionBCSNR is a safe treatment option for elderly breast cancer patients with clinically negative axillary lymph nodes.

Wood decay resistance (WDR) is marking the value of wood utilization. Many trees of the Lauraceae have exceptional WDR, as evidenced by their use in ancient royal palace buildings in China. However, the genetics of WDR remain elusive. Here, through comparative genomics, we revealed the unique characteristics related to the high WDR in Lauraceae trees. We present a 1.27-Gb chromosome-level assembly for Lindera megaphylla (Lauraceae). Comparative genomics integrating major groups of angiosperm revealed Lauraceae species have extensively shared gene microsynteny associated with the biosynthesis of specialized metabolites such as isoquinoline alkaloids, flavonoid, lignins and terpenoid, which play significant roles in WDR. In Lauraceae genomes, tandem and proximal duplications (TD/PD) significantly expanded the coding space of key enzymes of biosynthesis pathways related to WDR, which may enhance the decay resistance of wood by increasing the accumulation of these compounds. Among Lauraceae species, genes of WDR-related biosynthesis pathways showed remarkable expansion by TD/PD and conveyed unique and conserved motifs in their promoter and protein sequences, suggesting conserved gene collinearity, gene expansion and gene regulation supporting the high WDR. Our study thus reveals genomic profiles related to biochemical transitions among major plant groups and the genomic basis of WDR in the Lauraceae.

Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like behaviors. However, the molecular mechanisms underlying this disturbance remain elusive. Here, we showed that cyclin-dependent kinase 5 (Cdk5) was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing analysis. Serum levels of CDK5 also decreased in patients with Parkinson’s disease accompanied by motor symptoms. Moreover, Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. These symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+ channels (BK channels). Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient mice. Furthermore, CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of threonine-908. Restoration of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f mice. Together, these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuron-mediated motor function, providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.

The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS and that its enhancer resides in proximity to eNOS promoter in endothelial cells (ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS expression and EC function. Mechanistically, LEENE facilitates the recruitment of RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our findings unravel a new layer in eNOS regulation and provide novel insights into cardiovascular regulation involving endothelial function.

MicroRNAs (miRNAs) are short noncoding RNAs (20–25 nucleotides) that regulate gene expression posttranscriptionally. However, identification and characterization of miRNAs remain limited for conifer species. In this study, we applied transcriptome-wide miRNAs sequencing to a conifer species Platycladus orientalis, which is highly adaptable to a wide range of environmental adversities, including drought, barren soil, and mild salinity. A total of 17,181,542 raw reads were obtained from the Illumina sequencing platform; 31 conserved and 91 novel miRNAs were identified, and their unique characteristics were further analyzed. Ten randomly selected miRNAs were validated by quantificational real-time polymerase chain reaction. Through miRNA target predictions based on psRNATarget, 2331 unique mRNAs were predicted to be targets of P. orientalis miRNAs that involved in 187 metabolic pathways in KEGG database. These targets included not only important transcription factors (e.g., class III homeodomain leucine zipper targeted by por-miR166d) but also indispensable nontranscriptional factor proteins (i.e., por-miR482a-3p regulated nucleotide-binding site leucine-rich repeat protein). Interestingly, six miRNAs (por-miR16, -miR44, -miR60-5p, -miR69–3p, -miR166b-5p, and -miR395c) were found in adaptation-related pathways (e.g., drought), indicating their possible involved in this species’ stress-tolerance characteristics. The present study provided essential information for understanding the regulatory role of miRNAs in P. orientalis and sheds light on their possible use in tree improvement for stress tolerance.