Patent lifetime prediction using LightGBM with a customized loss.

Patent lifespan is commonly used as a quantitative measure in patent assessments. Patent holders maintain exclusive rights by paying significant maintenance fees, suggesting a strong correlation between a patent's lifespan and its business potential or economic value. Therefore, accurately forecasting the duration of a patent is of great significance. This study introduces a highly effective method that combines LightGBM, a sophisticated machine learning algorithm, with a customized loss function derived from Focal Loss. The purpose of this approach is to accurately predict the probability of a patent remaining valid until its maximum expiration date. This research differs from previous studies that have examined the various stages and phases of patents. Instead, it assesses the commercial viability of individual patents by considering their lifespan. The evaluation process utilizes a dataset consisting of 200,000 patents. The experimental results show a significant improvement in the performance of the model by combining Focal Loss with LightGBM. By incorporating Focal Loss into LightGBM, its ability to give priority to difficult instances during training is enhanced, resulting in an overall improvement in performance. This targeted approach enhances the model's ability to distinguish between different samples and its ability to recover from challenges by giving priority to difficult samples. As a result, it improves the model's accuracy in making predictions and its ability to apply those predictions to new data.

Discovery of PVD-06 as a Subtype-Selective and Efficient PTPN2 Degrader.

Protein tyrosine phosphatase nonreceptor Type 2 (PTPN2) is an attractive target for cancer immunotherapy. PTPN2 and another subtype of PTP1B are highly similar in structure, but their biological functions are distinct. Therefore, subtype-selective targeting of PTPN2 remains a challenge for researchers. Herein, the development of small molecular PTPN2 degraders based on a thiadiazolidinone dioxide-naphthalene scaffold and a VHL E3 ligase ligand is described, and the PTPN2/PTP1B subtype-selective degradation is achieved for the first time. The linker structure modifications led to the discovery of the subtype-selective PTPN2 degrader PVD-06 (PTPN2/PTP1B selective index > 60-fold), which also exhibits excellent proteome-wide degradation selectivity. PVD-06 induces PTPN2 degradation in a ubiquitination- and proteasome-dependent manner. It efficiently promotes T cell activation and amplifies IFN-γ-mediated B16F10 cell growth inhibition. This study provides a convenient chemical knockdown tool for PTPN2-related research and a paradigm for subtype-selective PTP degradation through nonspecific substrate-mimicking ligands, demonstrating the therapeutic potential of PTPN2 subtype-selective degradation.

High-altitude resident pulmonary edema induced by SARS-CoV-2 infection in children - A case series.

From December 2022 to January 2023, seven children aged ≤14 years and residing in an area at 2999 m without altitude change in the past month developed severe cough, dyspnea, cyanosis, and severe pulmonary lesions within 2-3 days after SARS-CoV-2 infection. They were diagnosed to have high-altitude resident pulmonary edema. They completely recovered following 4-7 days of treatment with oxygen inhalation, vasodilation, diuretics, and glucocorticoids.

MicroRNA-668-3p inhibits myoblast proliferation and differentiation by targeting Appl1.

BACKGROUND: Skeletal muscle is the largest tissue in the body, and it affects motion, metabolism and homeostasis. Skeletal muscle development comprises myoblast proliferation, fusion and differentiation to form myotubes, which subsequently form mature muscle fibres. This process is strictly regulated by a series of molecular networks. Increasing evidence has shown that noncoding RNAs, especially microRNAs (miRNAs), play vital roles in regulating skeletal muscle growth. Here, we showed that miR-668-3p is highly expressed in skeletal muscle. METHODS: Proliferating and differentiated C2C12 cells were transfected with miR-668-3p mimics and/or inhibitor, and the mRNA and protein levels of its target gene were evaluated by RT‒qPCR and Western blotting analysis. The targeting of Appl1 by miR-668-3p was confirmed by dual luciferase assay. The interdependence of miR-668-3p and Appl1 was verified by cotransfection of C2C12 cells. RESULTS: Our data reveal that miR-668-3p can inhibit myoblast proliferation and myogenic differentiation. Phosphotyrosine interacting with PH domain and leucine zipper 1 (Appl1) is a target gene of miR-668-3p, and it can promote myoblast proliferation and differentiation by activating the p38 MAPK pathway. Furthermore, the inhibitory effect of miR-668-3p on myoblast cell proliferation and myogenic differentiation could be rescued by Appl1. CONCLUSION: Our results indicate a new mechanism by which the miR-668-3p/Appl1/p38 MAPK pathway regulates skeletal muscle development.

Ethanol-Induced Flash Sintering of ZnO Ceramics at Room Temperature.

Ceramic flash sintering with a strong electric field at room temperature is the most attractive method. This paper presents the flash sintering of ZnO ceramics at room temperature by the application of a 3-kV/cm electric field after a dropwise addition of ethanol. This method is simple and easy to control. The density of the specimen exceeded 96% after 30 s of sintering. No significant difference was observed in the initiation voltage of flash sintering with and without the dropwise addition of ethanol. Ethanol burns upon dropwise addition, causing a discharge to first occur far from the location of the dropwise addition, followed by glowing and heating up, which causes the temperature of the entire specimen to rise.

Circular RNA screening identifies circMYLK4 as a regulator of fast/slow myofibers in porcine skeletal muscles.

The type of myofiber is related to the quality of meat. The slow oxidized myofiber helps to increase the tenderness and juiciness of muscle. Numerous studies have shown that circRNA plays a key role in skeletal muscle development. However, the role of circRNA in porcine skeletal myofiber types is unclear. In this study, we performed high-throughput RNA sequencing to study the differential expression of circRNA in the longissimus dorsi and the soleus muscle. A total of 40,757 circRNAs were identified, of which 181 were significantly different. Interestingly, some circRNAs were involved in metabolism pathways, AMPK, FoxO, and PI3K-Akt signaling pathways. Besides, we focused on a novel circRNA-circMYLK4. By injecting circMYLK4-AAV into piglets, we found that circMYLK4 significantly increased the mRNA and protein levels of the slow muscle marker genes. In summary, our study laid an essential foundation for further research of circRNA in myofiber type conversion and higher meat quality.

Runx1 is a tumor suppressor gene in the mouse gastrointestinal tract.

The Runx1 transcription factor plays an important role in tissue homeostasis through its effects on stem/progenitor cell populations and differentiation. The effect of Runx1 on epithelial differentiation of the secretory cell lineage of the colon was recently demonstrated. This study aimed to examine the role of Runx1 in tumor development in epithelial cells of the gastrointestinal tract. Conditional knockout mice that lacked Runx1 expression in epithelial cells of the GI tract were generated. These mice were crossed onto the Apc(Min) background, killed and their intestinal tumor phenotypes were compared with Apc(Min) Runx1 wild-type control mice. Apc-wild-type Runx1-mutant mice were also examined for tumor development. Colons from Runx1 knockout and wild-type mice were used for genome-wide mRNA expression analyses followed by gene-specific quantitative RT-PCR of whole colon and colon epithelium to identify Runx1 target genes. Runx1 deficiency in intestinal epithelial cells significantly enhanced tumorigenesis in Apc(Min) mice. Notably, epithelial Runx1 deficiency in Apc-wild-type mice was sufficient to cause tumor development. Absence of Runx1 was associated with global changes in the expression of genes involved in inflammation and intestinal metabolism, and with gene sets indicative of a metastatic phenotype and poor prognosis. Gene-specific analysis of Runx1-deficient colon epithelium revealed increased expression of genes linked to an expansion of the stem/progenitor cell population. These results identify Runx1 as a novel tumor suppressor gene for gastrointestinal tumors and support a role for Runx1 in maintaining the balance between the intestinal stem/progenitor cell population and epithelial differentiation of the GI tract.

[A two-step protocol for induction of rat adipose tissue-derived stem cells into neuron-like cells].

OBJECTIVE: To investigate the differentiation potential of rat adipose tissue-derived cells (ADSCs) into neuron-like cells in vitro using a two-step induction protocol. METHODS: ADSCs isolated from the epididymal fat pads in male SD rats by means of differential attachment were cultured in vitro and subjected to adipogenic induction. After flow cytometric identification of the cell surface antigens CD106, CD11b, CD45, CD49d, CD90 and CD29, the third-passage ADSCs were induced to transdifferentiate into neural stem cell (NSC)-like cells in DMEM/F12 medium containing 10 ng/ml basic fibroblast growth factor (bFGF), 20 ng/ml epidermal growth factor (EGF) and 2% B27. The resultant NSC-like cells were then induced to differentiate into neuron-like cells in the neurobasal medium containing 10 ng/ml brain-derived neurotrophic factor (BDNF), 10 ng/ml glial cell line-derived neurotrophic factor (GDNF) and 1 µmol/L retinoic acid (RA). Immunocytochemistry was employed to identify the expression of the cell surface markers nestin, MAP2 and NeuN. RESULTS: The isolated ADSCs were positive for CD90 and CD29, and oil red O staining of the induced adipose-like cells yielded positive results. The third-passage ADSCs induced for 7 days aggregated as floating cell spheres positive for NSC surface antigen nestin. Further induction in neurobasal medium for 4 h resulted in adhesion of the cell spheres and the formation of cell processes extending from some peripheral cells, suggesting a morphological resemblance to neurons. Most of the cells showed positivity for MAP2 and NeuN. CONCLUSION: ADSCs can be induced to differentiate into neuron-like cells in vitro under appropriate conditions.

[Correlation of snoring with attention deficit and hyperactivity-impulsivity in school age children from Changsha City].

OBJECTIVE: To investigate the prevalence of snoring in school age children from Changsha City, and study the correlation of snoring with attention deficit and hyperactivity-impulsivity. METHODS: A total of 1 736 children aged 6 to 12 years were randomly sampled from five districts in Changsha City. Their parents completed the questionnaires about children's sleep conditions and the Attention Deficit Hyperactivity Disorder Diagnostic Scale-Parent Version. RESULTS: The total incidence rate of frequent snoring was 5.7%. Boys had higher incidence of frequent snoring than girls (7.5% vs 3.8%; x2=18.782, p<0.01). The incidence of snoring in the 6-to 9-year-old group was higher than that of the 10-to 12-year-old group (x2=9.666, P<0.01). The incidence of daytime sleepiness in the snoring group was higher than that in the non-snoring group (31.5% vs 25.9%; x2=6.678, p<0.01). The incidences of larynx choking, sleep apnea, mouth breathing, hyperhidrosis, and awaking for unknown reasons or awaking by choke in the frequent snoring group were significantly higher than in the occasional snoring and the non-snoring groups (x2=37.035, 27.745, 51.341, 30.975, 45.972 respectively; all P<0.01). The incidences of attention deficit (31.3%) and hyperactivity-impulsivity (18.2%) in the frequent snoring group were the highest, followed by the occasional snoring (16.2% and 9.9% respectively) and the non-snoring groups (13.9% and 8.8% respectively). There were significant differences in the incidence of both attention deficit (x2=20.592, p<0.01) and hyperactivity-impulsivity (x2=9.067, p<0.05) between groups. CONCLUSIONS: There is a high incidence of snoring in school age children from Changsha City. Snoring is correlated to attention deficit and hyperactivity-impulsivity. It is essential to pay attention to the mental growth and behavioral problems in children with sleep snoring.

[Induced differentiation of rat adipose-derived stem cells into Schwann-like cells].

OBJECTIVE: To assess the differentiation potential of rat adipose-derived stem cells (ADSCs) into Schwann-like cells in vitro. METHODS: ADSCs isolated from adult SD rats were cultured in vitro and identified with the cell surface antigens CD44, CD49d and CD106 by immunocytochemistry. The ADSCs of the sixth to eighth passages were inoculated in polylysine-coated culture plate and cultured for 12 days in DMEM/F12 culture medium containing 10% fetal bovine serum, 5 ng/ml platelet-derived growth factor, 10 ng/ml basic fibroblast growth factor, 14 micromol/L Forskolin and 200 ng/ml Heregulin to induce their differentiation in vitro. Immunocytochemistry was performed to identify the expression of the cell surface markers nestin, glial fibrillary acidic protein (GFAP), S-100, and P75. RESULTS: The isolated and purified ADSCs were positive for CD44 and CD49d expressions but negative for CD106. After 12 days of culture in the conditional culture medium, most of the cells showed positive expressions of GFAP, S-100, and P75, the specific protein markers of Schwann cells. CONCLUSION: Adult rat ADSCs are confirmed to have potentials of neuroglial differentiation and capable of differentiating into Schwann-like cells in vitro.

Prostate stem cell antigen mRNA expression in preoperatively negative biopsy specimens predicts subsequent cancer after transurethral resection of the prostate for benign prostatic hyperplasia.

BACKGROUND: Recent data showed that prostate stem cell antigen (PSCA) mRNA expression in transurethral resection of the prostate (TURP)-resected tissues predicted the subsequent prostate cancer after TURP in benign prostatic hyperplasia (BPH) patients with both PSA < 4.0 ng/ml and normal DRE findings. This study was to determine whether PSCA mRNA positivity in preoperatively negative prostatic biopsy samples from BPH men with PSA > 4.0 ng/ml and/or suspicious DRE findings had predictive performance following TURP. MATERIALS AND METHODS: PSCA in situ hybridization was performed on negative prostatic biopsies taken before TURP from 166 enrolled symptomatic BPH patients, who were continuously followed for 5 years postoperatively. Predictive performance of PSCA mRNA for subsequent cancer onset was evaluated by univariate and multivariate Cox proportional hazards models with bootstrapping and concordance indices. RESULTS: PSCA mRNA was detected in 42/166 (25.3%) of the preoperatively negative biopsy specimens, with a mean positive-labeling cells of 31.6%, in which 31 patients were identified as having subsequent PCa on follow-up. Of 124 patients with negative expression for PSCA mRNA none were subsequently diagnosed with PCa. The examination of Spearman's rank correlation coefficient showed that PSCA mRNA expression levels were positively and statistically correlated with higher Gleason score (r = 0.88, P < 0.001) and clinical T stage (r = 0.84, P < 0.001). A final multivariate Cox proportional hazards model demonstrated that only PSCA mRNA expression in negative prostatic biopsies was predictive of the subsequent cancer development after TURP (hazard ratio = 3.49; 95% CI: 2.02-4.75; P < 0.001), with the concordance index of 0.893. CONCLUSIONS: This prospective study identifies PSCA mRNA in preoperatively negative prostatic biopsies as a significant predictor of subsequent cancer after TURP.