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Abstract Background Primary malignant neoplasms of the spermatic cord are extremely rare, with most reported cases being sarcomas or metastatic carcinomas. However, primary adenocarcinoma of the spermatic cord has not been previously reported. Case presentation A 34-year-old male with a solid mass in the right spermatic cord, was eventually diagnosed with primary adenocarcinoma. Histological examination revealed a moderately-to-poorly differentiated adenocarcinoma exhibiting glandular, cribriform, or nested growth patterns, characterized by medium to large-sized cells and focal extracellular mucus. Immunohistochemical analysis demonstrated positive staining for CK (AE1/AE3), CK8/18, CK19, MOC31 (EP-CAM), and Ber-EP4, while negative staining was observed for CK7, D2-40, WT-1, MC, PAX-8, NKX3.1, PSA, CEA, TTF-1, and NapsinA. Furthermore, a complete loss of INI-1 expression and consistent BRG1 expression were noted in all tumor cells. Next-generation sequencing revealed SMARCB1 deletion, low tumor mutation burden (TMB-L), and microsatellite stability (MSS). Conclusion We reported the first case of primary adenocarcinoma of the spermatic cord with SMARCB1 (INI-1) deficiency. This case contributes to the expanding understanding of rare neoplasms and underscores the importance of further research into therapeutic strategies targeting SMARCB1-deficient tumors.

Abstract Background Pre-clinical data suggests a potential synergistic effect of eribulin and platinum. However, clinical data on the combination for metastatic breast cancer (mBC) is lacking. We evaluated the efficacy and safety of eribulin plus carboplatin (ErCb) in patients with mBC. Patients and methods This multicenter, real-world cohort study included patients with pre-treated metastatic triple negative breast cancer (TNBC) or endocrine-refractory hormone receptor (HR) positive, HER2-negative mBC who received ErCb. Eribulin (1.4 mg/m2) and carboplatin (target AUC = 2) were administered intravenously on day 1 and 8 of 21-day cycle. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results From March 2022 to December 2023, a cohort of 37 patients were recruited to the study. Among them, 22 patients have TNBC and 15 have HR + HER2 − mBC. Of the 22 patients with TNBC, 8 had an initial diagnosis of the HR + HER2 − subtype. The median treatment was 6 cycles (range, 2 − 8 cycles). In the full cohort, TNBC, and HR + HER2 − subgroup, the ORR were 51.4%, 54.5% and 46.7%, the DCR were 81.1%, 81.8% and 80%, and the median PFS were 5 months, 5 months, and 5.2 months, respectively. The median OS was 12.7 months in the entire cohort and 12.8 months in TNBC subgroup. The most common grade 3/4 hematological AEs were neutropenia (37.8%), leukopenia (35.1%), febrile neutropenia (10.8%), thrombocytopenia (5.4%), and anemia (2.7%). No grade 3/4 non-hematological AEs were observed. Conclusion ErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.

Abstract Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients are at a high risk of developing metastases in the brain. However, research focusing on treatment strategies for hormonal receptor positive (HR+), HER2+ BC patients with brain metastases (BM) remains limited. Thus, a multi-center, prospective trial was conducted in China. Women over the age of 18 who were naive to whole brain radiotherapy and had estrogen receptor (ER)/progesterone-receptor (PgR) positive, HER2+ BM were treated with palbociclib, fulvestrant, trastuzumab and pyrotinib, until disease progression or the development of intolerable side effects. The primary endpoint was objective response rate (ORR) in the central nervous system (CNS). This ongoing study is still recruiting participants and is registered with ClinicalTrials.gov (NCT04334330). This report presents the findings from an interim analysis. From December 4, 2020, to November 2, 2022, 15 patients were enrolled. Among the 14 patients who were evaluable for clinical response, the ORR was 35.7% (95% CI: 12.8–64.9%), with a CNS–ORR of 28.6% (95% CI: 8.4–58.1%). The median follow-up period was 6.3 months (range, 2.1–14.3 months), during which the median progression-free survival (PFS) was 10.6 months (95% CI: 4.3–16.9 months), and the median time to CNS progression was 8.5 months (95% CI: 5.9–11.1 months). The most common adverse event was diarrhea (93%), with 33% having grade 3 and 6.7% having grade 4. The study suggests that the combination of palbociclib, trastuzumab, pyrotinib and fulvestrant offers a promising chemo-free treatment strategy for HR+, HER2+ BC patients with BM.

This study aimed to investigate the changes in physicochemical properties, bioactivities and metabolites of fermented goji juice (FGJ) by Lacticaseibacillus rhamnosus at different fermentation stages. The results showed that Lacticaseibacillus rhamnosus fermentation significantly decreased the content of soluble protein, total phenolic, total flavonoid and total sugar. Meanwhile, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability and the inhibition rate of xanthine oxidase (XOD) activity were remarkably enhanced by Lacticaseibacillus rhamnosus fermentation. Flavor profiles analysis indicated that FGJ produced novel volatile compounds such as 4-methylpentanol and 2-butanol, which provide its distinct aroma. The non-targeted metabolomics analysis showed that the differential metabolites in the FGJ28 vs. FGJ0 group were mainly included 1,7-bis (3,4-dihydroxyphenyl) heptan-3-yl acetate, isoplumbagin, triacetylresveratrol, sulochrin, indole-3-acetaldehyde, etc., which might have an effect on the promotion of the bioactivity of goji juice. These findings will contribute to understanding the biotransformation effect of Lacticaseibacillus rhamnosus fermentation on goji juice.

Abstract Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING‑deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

Abstract Background Malnutrition is severely associated with worst prognosis of patients with heart failure (HF). Malnourished patients with the metabolic syndrome (MS) can result in a double burden of malnutrition. We aimed to investigate the impact of the MS on clinical outcomes in malnourished HF patients. Methods We examined 529 HF patients at risk of malnutrition with a mean age of (66 ± 10) years and 78% (415) were male. Nutritional status defined primarily by the prognostic nutritional index (PNI), with PNI

Abstract Background Identifying breast cancer (BC) patients with germline breast cancer susceptibility gene (gBRCA) mutation is important. The current criteria for germline testing for BC remain controversial. This study aimed to develop a nomogram incorporating ultrasound radiomic features and clinicopathological factors to predict gBRCA mutations in patients with BC. Materials and methods In this retrospective study, 497 women with BC who underwent gBRCA genetic testing from March 2013 to May 2022 were included, including 348 for training (84 with and 264 without a gBRCA mutation) and 149 for validation(36 patients with and 113 without a gBRCA mutation). Factors associated with gBRCA mutations were identified to establish a clinicopathological model. Radiomics features were extracted from the intratumoral and peritumoral regions (3 mm and 5 mm) of each image. The least absolute shrinkage and selection operator regression algorithm was used to select the features and logistic regression analysis was used to construct three imaging models. Finally, a nomogram that combined clinicopathological and radiomics features was developed. The models were evaluated based on the area under the receiver operating characteristic curve (AUC), calibration, and clinical usefulness. Results Age at diagnosis, family history of BC, personal history of other BRCA-related cancers, and human epidermal growth factor receptor 2 status were independent predictors of the clinicopathological model. The AUC of the imaging radiomics model combining intratumoral and peritumoral 3 mm areas in the validation set was 0.783 (95% confidence interval [CI]: 0.702—0.862), which showed the best performance among three imaging models. The nomogram yielded better performance than the clinicopathological model in validation sets (AUC: 0.824 [0.755—0.894] versus 0.659 [0.563—0.755], p = 0.007). Conclusion The nomogram based on ultrasound images and clinicopathological factors performs well in predicting gBRCA mutations in BC patients and may help to improve clinical decisions about genetic testing.

Purpose: The limited understanding of long-term estradiol (E2) suppression poses challenges to the effectiveness of adjuvant therapy with aromatase inhibitors (AI), necessitating comprehensive serum E2 monitoring to address this issue. Therefore, our objective was to investigate serum E2 levels in women undergoing adjuvant AI treatment and evaluate the significance of such monitoring. Patients and methods: In this prospective cohort study, we recruited women who had received adjuvant AI treatment, including those who underwent ovarian function suppression (OFS). Serum E2 levels were measured using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The primary endpoint was the proportion of women with E2 levels exceeding 2.72 pg/mL, indicating inadequate suppression achieved with AI therapy. Results: A total of 706 patients were enrolled, including 482 women with OFS in combination with AI. Among them, 116 women (16.4 %) exhibited E2 levels exceeding 2.72 pg/mL. The majority of serum E2 elevations (77.6 %) occurred within the first two years of initiating endocrine therapy. Younger age, no prior chemotherapy, shorter duration of the current treatment regimen, and lower follicle stimulating hormone (FSH) levels were associated with inadequate E2 suppression. Serum E2 concentrations demonstrated dynamic variations and occasional rebound following adjuvant AI therapy. Conclusions: Despite receiving adjuvant AI treatment for nearly two years, a certain proportion of patients failed to achieve the adequate threshold of E2 suppression. Our findings emphasize the significance of monitoring serum E2 levels during adjuvant AI therapy, particularly within the first two years. Further research is imperative to facilitate a more comprehensive comprehension of E2 monitoring.

Electroencephalographic Neurofeedback Training (EEG NFT) aims to improve sport performance by teaching athletes to control their mental states, leading to better cognitive, emotional, and physical outcomes. The psychomotor efficiency hypothesis suggests that optimizing brain function could enhance athletic ability, indicating the potential of EEG NFT. However, evidence for EEG-NFT’s ability to alter critical brain activity patterns, such as sensorimotor rhythm and frontal midline theta—key for concentration and relaxation—is not fully established. Current research lacks standardized methods and comprehensive studies. This shortfall is due to inconsistent EEG target selection and insufficient focus on coherence in training. This review aims to provide empirical support for EEG target selection, conduct detailed control analyses, and examine the specificity of electrodes and frequencies to relation to the psychomotor efficiency hypothesis. Following the PRISMA method, 2,869 empirical studies were identified from PubMed, Science Direct, Web of Science, Embase, CNKI, and PsycINFO. Thirteen studies met the inclusion criteria: (i) proficient skill levels; (ii) use of EEG; (iii) neurofeedback training (NFT); (iv) motor performance metrics (reaction time, precision, dexterity, balance); (v) control group for NFT comparison; (vi) peer-reviewed English-language publication; and (vii) randomized controlled trial (RCT) design. Studies indicate that NFT can enhance sports performance, including improvements in shooting accuracy, golf putting, and overall motor skills, as supported by the psychomotor efficiency hypothesis. EEG NFT demonstrates potential in enhancing sports performance by optimizing performers’ mental states and psychomotor efficiency. However, the current body of research is hampered by inconsistent methodologies and a lack of standardized EEG target selection. To strengthen the empirical evidence supporting EEG NFT, future studies need to focus on standardizing target selection, employing rigorous control analyses, and investigating underexplored EEG markers. These steps are vital to bolster the evidence for EEG NFT and enhance its effectiveness in boosting sport performance.

Abstract Electromagnetic ion cyclotron (EMIC) waves are a key plasma mode affecting radiation belt dynamics. These waves are important for relativistic electron losses through scattering and precipitation into Earth's ionosphere. Although theoretical models of such resonant scattering predict a low‐energy cut‐off of ∼1 MeV for precipitating electrons, observations from low‐altitude spacecraft often show simultaneous relativistic and sub‐relativistic electron precipitation associated with EMIC waves. Recently, nonresonant electron scattering by EMIC waves has been proposed as a possible solution to the above discrepancy. We employ this model and a large database of EMIC waves to develop a universal treatment of electron interactions with EMIC waves, including nonresonant effects. We use the Green's function approach to generalize EMIC diffusion rates foregoing the need to modify existing codes or recompute empirical wave databases. Comparison with observations from the electron losses and fields investigation mission demonstrates the efficacy of the proposed method for explaining sub‐relativistic electron losses by EMIC waves.

This research presents and examines the first power and speed adaptive 60 GHz receiver, combining the potential of high data rates with low energy consumption. Hence, enabling a range of Tactile Internet applications such as a compact wireless robotic skin. Designed and fabricated in a 22 nm fully depleted silicon-on-insulator (FD-SOI) CMOS process, the required area is only 0.67 mm2. Low energy consumption is achieved by using on-off keying (OOK) and aggressive duty cycling. For data rates up to 25 Mbps, synchronization is achieved by oversampling. In this case, the sampling clock is directly related to the data rate. The duty cycle is generated from the sampling clock and defines the average energy consumption. Consequently, a truly data rate dependent energy consumption can be achieved, which is especially beneficial in low communication load scenarios. At a maximum data rate of 2.8 Gbps, the energy consumption is 15.3 mW, while at 25 kbps the receiver consumes only $\mathrm {1.1~\mu \text {W} }$ . Moreover, the achieved sensitivity is -20.5 dBm at 2.8 Gbps for a bit error rate (BER) below 1E-12 and -25 dBm at 25 kbps respectively.

Takifugu rubripes are warm temperate fish, suggesting that the reduced seawater temperatures in winter are likely to have a substantial impact on their survival. Considering this, there is likely to be some industrial value in breeding extremely low-temperature tolerant varieties of this fish. Here, we evaluate the expression changes in six major QTL candidate genes (tacc2, fsip1, exoc4, arhgap44a, pde10a, and unc5b) in response to reduced temperature in an effort to understand cold tolerance in T. rubripes. The expression changes of these six genes in the liver, heart, and kidney were detected using real-time quantitative PCR. This study used three groups of 8-month-old fish, all from the same family established by our research group, exposed to three different temperature gradients, where 8 ℃ and 13 ℃ acted as the minimum in the low temperature groups and 18 ℃ acted as the minimum in the control group. Our results showed that all six genes were expressed at different levels across each of these three tissues at different temperatures. The relative expression of pde10a first increased and then decreased in all three tissues, whereas the relative expression of tacc2 and exoc4 were distinctly different in the liver, kidney, and heart at 8 ℃. In this case, these transcripts first decreased and then stabilized in the liver, increased and then stabilized in the kidneys, and increased and then decreased in the heart. The relative expression of unc5b was low in the liver and heart, but high in the kidney following a second week of low-temperature growth, whereas arhgap44a expression was slightly upregulated in the liver and stable in the kidney and heart. fsip1 expression demonstrated a downward trend in the liver but seemed to first increase and then decrease in the heart and kidney. Taken together, these results demonstrate that all six of these genes are differentially expressed in different tissues of T. rubripes, with these differences exhibiting dynamic changes with respect to tissue origin and temperature. In addition, this data clearly revealed a positive correlation between cold stress and the expression of these QTL candidate genes. Thus, we can conclude that these six QTL candidate genes may play a substantial role in the low temperature adaptation of T. rubripes. This is significant because although low temperature is known to be an important factor limiting the development of the industrial utility of T. rubripes, there are still relatively few reports describing their cold stress response. This study provides a theoretical basis for the study of signaling pathways related to the low temperature tolerance response of T. rubripes and the development of low temperature tolerant varieties.

The maturation of wheat flour is a transformative process that elevates its processing and culinary attributes to their peak performance levels. Despite extensive research on starch and gluten protein modifications, the impact of lipid changes has been largely unexplored. This study addresses this gap by examining the maturation of freshly milled wheat flour at 15 °C, 25 °C, and 40 °C over 60 days, focusing on enzymatic activities—lipase, lipoxidase, and catalase—and lipid metabolites, including free fatty acids, conjugated trienes, p-anisidine value, and total oxidation value. The results of this study showed that free fatty acids continued to increase at all temperatures, with the most significant increase of 50% at 15 °C. The p-anisidine value followed a pattern of initial increase followed by a decline, while conjugated trienes were markedly higher at 40 °C, suggesting temperature’s significant influence on lipid peroxidation. Notably, total oxidation values became erratic post 30 days, indicating a shift in oxidative dynamics. This study underscores the correlation between lipid metabolites and enzymatic activities, revealing the enzymes’ pivotal role in lipid oxidation. The interplay of temperature and time offers valuable insights for optimizing wheat flour maturation, ensuring superior quality for various applications.

Recent years small object detection has seen remarkable advancement. However, small objects are difficult to accurately detect in complex scenes due to their low resolution. The downsampling operation inevitably leads to the loss of information for small objects. In order to solve these issues, this article proposes a novel Multi-branch Attention Network (MBAN) to improve the detection performance of small objects. Firstly, an innovative Multi-branch Attention Module (MBAM) is proposed, which consists of two parts, i.e. Multi-branch structure consisting of convolution and maxpooling, and the parameter-free SimAM attention mechanism. By combining these two parts, the number of network parameters is reduced, the information loss of small objects is reduced, and the representation of small object features is enhanced. Furthermore, to systematically solve the problem of small object localization, a pre-processing method called Adaptive Clustering Relocation (ACR) is proposed. To validate our network, we conducted extensive experiments on two benchmark datasets, i.e. NWPU VHR-10 and PASCAL VOC. The findings from the experiment demonstrates the significant performance gains of MBAN over most existing algorithms, the mAP of MBAN achieved 96.55% and 84.96% on NWPU VHR-10 and PASCAL VOC datasets, respectively, which proves that MBAN has significant performance in small object detection.

Abstract Background Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). Methods We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. Results Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84–21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08–0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. Conclusions Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC.

Abstract Background Several proteins in the tripartite-motif (TRIM) family are associated with the development of colorectal cancer (CRC), but research on the role of TRIM69 was lacking. The present study examined the correlation between TRIM69 expression and colon adenocarcinoma (COAD). Methods mRNA sequencing data for COAD patients was extracted from The Cancer Genome Atlas to analyze correlations between TRIM69 expression and patients’ clinical features as well as survival. Potential associations with immune cells and chemosensitivity also were predicted using various algorithms in the TIMER, Limma, clusterProfiler, GeneMANIA, and Gene Set Cancer Analysis platforms. Subsequently, polymerase chain reaction analysis and immunohistochemical staining were used to detect TRIM69 expression in COAD tissue samples from real-world patients. Results TRIM69 expression was lower in COAD tissues than in normal tissues and correlated with the pathologic stage and metastasis (M category). Additionally, TRIM69 was found to be involved in several immune-related pathways, notably the NOD-like signaling pathway. These results suggest that high TRIM69 expression has the potential to enhance tumor sensitivity to 5-fluorouracil and programmed cell death protein 1 (PD-1) blockers. Conclusions From our findings that TRIM69 expression was significantly reduced in COAD compared with non-cancer tissues and associated with pathologic stage and metastasis, we conclude that increasing TRIM69 expression and/or activity may help to improve therapeutic outcomes. Accordingly, TRIM69 represents a potentially valuable marker of metastasis and target for adjuvant therapy in COAD.

Abstract Rituximab, a chimeric anti-CD20 monoclonal antibody, is an effective treatment for nephrotic syndrome. Hypokalemia is a rare adverse reaction among patients treated with rituximab although there have been extensive reports of acute and chronic adverse events with the administration of rituximab. We herein report two cases of symptomatic hypokalemia after intravenous rituximab administration in our center, to help health professionals consider the possibility of acute hypokalemia after rituximab administration, monitor potassium timely and develop an appropriate treatment plan.

Abstract Background Genetic testing plays an important role in guiding screening, diagnosis, and precision treatment of breast cancer (BC). However, the appropriate genetic testing criteria remain controversial. The current study aims to facilitate the development of suitable strategies by analyzing the germline mutational profiles and clinicopathological features of large‐scale Chinese BC patients. Methods BC patients who had undergone genetic testing at the Sun Yat‐sen University Cancer Center (SYSUCC) from September 2014 to March 2022 were retrospectively reviewed. Different screening criteria were applied and compared in the population cohort. Results A total of 1035 BC patients were enrolled, 237 pathogenic or likely pathogenic variants (P/LPV) were identified in 235 patients, including 41 out of 203 (19.6%) patients tested only for BRCA1/2 genes, and 194 out of 832 (23.3%) received 21 genes panel testing. Among the 235 P/LPV carriers, 222 (94.5%) met the NCCN high‐risk criteria, and 13 (5.5%) did not. While using Desai's criteria of testing, all females diagnosed with BC by 60 years and NCCN criteria for older patients, 234 (99.6%) met the high‐risk standard, and only one did not. The 21 genes panel testing identified 4.9% of non‐BRCA P/LPVs and a significantly high rate of variants of uncertain significance (VUSs) (33.9%). The most common non‐BRCA P/LPVs were PALB2 (11, 1.3%), TP53 (10, 1.2%), PTEN (3, 0.4%), CHEK2 (3, 0.4%), ATM (3, 0.4%), BARD1 (3, 0.4%), and RAD51C (2, 0.2%). Compared with BRCA1/2 P/LPVs, non‐BRCA P/LPVs showed a significantly low incidence of NCCN criteria listed family history, second primary cancer, and different molecular subtypes. Conclusions Desai's criteria might be a more appropriate genetic testing strategy for Chinese BC patients. Panel testing could identify more non‐BRCA P/LPVs than BRCA1/2 testing alone. Compared with BRCA1/2 P/LPVs, non‐BRCA P/LPVs exhibited different personal and family histories of cancer and molecular subtype distributions. The optimal genetic testing strategy for BC still needs to be investigated with larger continuous population studies.

Beef is an important high-nutrition livestock product, and several byproducts, such as bovine cartilage, are produced during slaughter. To effectively utilize these agricultural and pastoral byproducts, combined (trypsin-papain) enzymolysis and cetylpyridine chloride purification methods were used to obtain chondroitin sulfate (CS) from the nasal cartilage of Shaanxi Yellow cattle. The effects of pH, temperature, and time on the CS yield during enzymatic hydrolysis were investigated, and the CS extraction process was optimized using response surface methodology. The best yield of CS was 21.62% under the optimum conditions of pH 6.51, temperature of 64.53°C, and enzymolysis time of 19.86 h. The molecular weight of CS from Shaanxi cattle nasal cartilage was 89.21 kDa, glucuronic acid content was 31.76±0.72%, protein content was 1.12±0.03%, and sulfate group content was 23.34±0.08%. The nasal cartilage CS of the Yellow cattle showed strong DPPH•, •OH, and ABTS+• radical scavenging abilities and ferrous reduction ability in the experimental concentration range. This study could contribute to “turn waste into treasure” and improve the comprehensive utilization of regional characteristic biological resources.

The panel vector autoregression (PVAR) model preserves the advantages of the vector autoregression model while expanding its time series to the spatial direction, which can effectively solve the problem of individual heterogeneity using panel data. It is derived from econometrics but has been applied interdisciplinarily because of its advantages in metrology. Given its increasingly important role in econometrics and interdisciplinary applications, a systematic review based on the bibliometric tool was conducted by screening 292 articles related to PVAR from the Web of Science. First, a descriptive analysis of the related articles was conducted to identify the current research status of PVAR. It reveals that macroeconomic effects, economic growth and environmental protection, and model adaptation are the primary topics in PVAR-related research. Then, the study classifies PVAR models into three categories and summarizes the four estimation methods within the knowledge domain. Having clarity on the different categories and estimation methods enhances the practical utility of the PVAR model. Finally, to gain insight into the knowledge evolution of PVAR, this study discusses how research hotspots in the field have evolved over time. This analysis provides a historical perspective and allows researchers to anticipate future trends and emerging areas of interest within PVAR. Based on these findings, this study identifies three research opportunities that can guide future investigations in the field of PVAR. This study aims to foster extension applications of the model in econometric research and highlight its potential for interdisciplinary applications.

Abstract Background Cervical cancer is an important public health problem. Conventional colposcopy is inefficient in the diagnosis of cervical lesions and massive biopsies result in trauma. There is an urgent need for a new clinical strategy to triage women with abnormal cervical screening results immediately and effectively. In this study, the high-resolution microendoscopy combined with methylene blue cell staining technology was used to perform real-time in vivo imaging of the cervix for the first time. Methods A total of 41 patients were enrolled in the study. All patients underwent routine colposcopy and cervical biopsy, and high-resolution images of methylene blue-stained cervical lesions were obtained in vivo using microendoscopy. The cell morphological features of benign and neoplastic cervical lesions stained with methylene blue under microendoscopy were analyzed and summarized. The microendoscopy and histopathology findings of the high-grade squamous intraepithelial lesion (HSIL) and more severe lesions were compared. Results The overall consistency of microendoscopy diagnosis with pathological diagnosis was 95.12% (39/41). Diagnostic cell morphological features of cervicitis, low-grade squamous intraepithelial lesion (LSIL), HSIL, adenocarcinoma in situ, and invasive cancer were clearly demonstrated in methylene blue stained microendoscopic images. In HSIL and more severe lesions, microendoscopic methylene blue cell staining technology can show the microscopic diagnostic features consistent with histopathology. Conclusions This study was an initial exercise in the application of the microendoscopy imaging system combined with methylene blue cell staining technology to cervical precancerous lesions and cervical cancer screening. The results provided the basis for a novel clinical strategy for triage of women with abnormal cervical screening results using in vivo non-invasive optical diagnosis technology.

Abstract We investigate electrostatic waves in a magnetopause reconnection event around a secondary electron diffusion region. Near the current sheet mid‐plane, parallel electron beam‐mode waves are modulated by whistler waves. We conclude that the anisotropy of energized electrons in the reconnection exhaust excites whistler waves, which produce spatially modulated electron beams through nonlinear Landau resonance, and these beams excite beam‐mode electrostatic waves. In the separatrix region, parallel propagating electrostatic waves associated with field‐aligned electron beams and perpendicular propagating electron cyclotron harmonic waves with loss cone distributions exhibit modulation frequencies in the lower‐hybrid wave (LHW) frequency range. We infer that LHWs scatter electrons to produce beams and alter loss cones to modulate electrostatic waves. The results advance our understanding about the regimes and mechanisms of electrostatic waves in reconnection, with an emphasis on their coupling with lower‐frequency electromagnetic waves.

Background Although surgical methods are the most effective treatments for colon adenocarcinoma (COAD), the cure rates remain low, and recurrence rates remain high. Furthermore, platelet adhesion-related genes are gaining attention as potential regulators of tumorigenesis. Therefore, identifying the mechanisms responsible for the regulation of these genes in patients with COAD has become important. The present study aims to investigate the underlying mechanisms of platelet adhesion-related genes in COAD patients. Methods The present study was an experimental study. Initially, the effects of platelet number and related genomic alteration on survival were explored using real-world data and the cBioPortal database, respectively. Then, the differentially expressed platelet adhesion-related genes of COAD were analyzed using the TCGA database, and patients were further classified by employing the non-negative matrix factorization (NMF) analysis method. Afterward, some of the clinical and expression characteristics were analyzed between clusters. Finally, least absolute shrinkage and selection operator regression analysis was used to establish the prognostic nomogram. All data analyses were performed using the R package. Results High platelet counts are associated with worse survival in real-world patients, and alternations to platelet adhesion-related genes have resulted in poorer prognoses, based on online data. Based on platelet adhesion-related genes, patients with COAD were classified into two clusters by NMF-based clustering analysis. Cluster2 had a better overall survival, when compared to Cluster1. The gene copy number and enrichment analysis results revealed that two pathways were differentially enriched. In addition, the differentially expressed genes between these two clusters were enriched for POU6F1 in the transcription factor signaling pathway, and for MATN3 in the ceRNA network. Finally, a prognostic nomogram, which included the ALOX12 and ACTG1 genes, was established based on the platelet adhesion-related genes, with a concordance (C) index of 0.879 (0.848–0.910). Conclusion The mRNA expression-based NMF was used to reveal the potential role of platelet adhesion-related genes in COAD. The series of experiments revealed the feasibility of targeting platelet adhesion-associated gene therapy.

The sensor network for intelligent roadways, comprised of devices like cameras, laser radars, millimeter-wave radars, and weather stations, is an integral part of the roadside digital infrastructure. One of the main challenges in building intelligent highway sensor networks is to create a controllable, manageable, and useable sensor network with multi-modal sensors deployed on highways. This network should not only facilitate global and scene sensing but also enable collaborative sensing and control functions. Therefore, this study aims to define the concept, main features, and technical connotation of Vehicle-Infrastructure Cooperative Intelligent Driving (VICID). It also outlines the development of a cloud-native cloud control platform for intelligent roadways and refines the technology requirements and indices. This platform is designed to support open services for innovative applications, such as addressing bottlenecks, managing roadworks zones, and implementing dynamic lane assignments for automated driving. Lastly, we introduce Beijing's highway pilot projects, which can serve as a guide and reference for designing and constructing sensor network equipment for intelligent roadways in China, as well as for key technology research and development.

Abstract The prognosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) remained unsatisfactory currently, more anti-HER2 agents are needed. Here we report a phase I study that evaluated the safety, activity, and biomarkers of LZM005, a HER2 antibody, used as a monotherapy or in combination with trastuzumab plus docetaxel in patients with HER2-positive MBC. From October 2017 to December 2019, 34 patients received LZM005 (14 monotherapy, 20 combination therapy). No DLT was observed. The common adverse events (AEs) in phase Ia included diarrhea (21.4%), infusion reaction (21.4%), and hypertriglyceridemia (21.4%), while those in phase Ib were leukopenia (85.0%), neutropenia (75.0%), anemia (60.0%), diarrhea (60.0%), and rash/pruritus (50.0%). All AEs were manageable. In phase Ia, partial response (PR) was achieved in one case (1/14, overall response rate [ORR]: 7.1%); the disease control rate was 42.90% (6/14). In phase Ib, 11 patients (55.0%) achieved PR, and eight (40.0%) had stable disease. The ORR was 100% (6/6) in trastuzumab-naive and 35.7% (5/14) in trastuzumab-pretreated patients. Biomarker analysis showed that chromatin remodeling genes KMT2B and BRWD1 were associated with better progression-free survival. LZM005 is well tolerated and shows potent activity in patients with HER2-positive MBC.

Introduction: IgA nephropathy (IgAN) is the most common disease leading to end-stage renal disease, and tubular fibrosis represents an important risk factor for disease progression. However, research on early molecular diagnostic indicators of tubular fibrosis and the mechanisms underlying disease progression is still lacking.Methods: The GSE93798 dataset was downloaded from the GEO database. DEGs were screened and analyzed for GO and KEGG enrichment in IgAN. The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithms were applied to screen for hub secretory genes. The expression and diagnostic efficacy of hub genes were confirmed by the GSE35487 dataset. ELISA was applied to detect the expression of APOC1 in serum. The expression and localization of hub genes in IgAN were verified by the expression of IHC and IF in human kidney tissues, and the correlation of expression with clinical data was verified in the Nephroseq database. Finally, cellular experiments clarified the role of hub genes in the signaling pathway.Results: A total of 339 DEGs were identified in IgAN, of which 237 were upregulated and 102 downregulated. The KEGG signaling pathway is enriched in the ECM–receptor interaction and AGE-RAGE signaling pathway. APOC1, ALB, CCL8, CXCL2, SRPX2, and TGFBI identified six hub secretory genes using the LASSO and SVM-RFE algorithms. In vivo and in vitro experiments demonstrated that APOC1 expression was elevated in IgAN. The serum concentration of APOC1 was 1.232 ± 0.1812 μg/ml in IgAN patients, whereas it was 0.3956 ± 0.1233 μg/ml in healthy individuals. APOC1 exhibited high diagnostic efficacy for IgAN (AUC of 99.091%, specificity of 95.455%, and sensitivity of 99.141%) in the GSE93798 dataset. APOC1 expression negatively correlated with eGFR (R2 = 0.2285, p = 0.0385) and positively correlated with serum creatinine (R2 = 0.41, p = 0.000567) in IgAN. APOC1 exacerbated renal fibrosis, possibly in part by activating the NF-κB pathway in IgAN.Conclusion: APOC1 was identified as the core secretory gene of IgAN, which was closely associated with blood creatinine and eGFR and had significant efficacy in the diagnosis of IgAN. Mechanistic studies revealed that the knockdown of APOC1 could improve IgAN renal fibrosis by inhibiting the NF pathway, which may be a potential therapeutic target for improving renal fibrosis in IgAN.

The graph isomorphism, as a key task in graph data analysis, is of great significance for the understanding, feature extraction, and pattern recognition of graph data. The best performance of traditional methods is the quasi-polynomial time complexity, which is infeasible for huge graphs. This paper aims to propose a lightweight graph network to resolve the problem of isomorphism in huge graphs. We propose a partitioning algorithm with linear time complexity based on isomorphic necessary condition to handle network graphs that cannot be fully computed by a single computer. We use anti-weight convolution analysis and skip connections to obtain a more stable representation with fewer layers and parameters. We implement simulations on personal computer (PC) with graphs consisting of hundred millions of edges, demonstrating the identification performance ( $ \gt\!\!98\%$ ) and time efficiency.

With the construction and application of more and more intelligent networking demonstration projects, a large number of advanced roadside digital infrastructures are deployed on both sides of the intelligent road. These devices sense the road situation in real time through algorithms and transmit it to edge computing units and cloud control platforms through high-speed optical fiber transmission networks. This article proposes a cloud edge terminal architecture system based on cloud edge cooperation, as well as a data exchange protocol for cloud control basic platforms. The over-the-horizon scene division and optical fiber network communication model are verified by deploying intelligent roadside devices on the intelligent highway. At the same time, this article uses the optical fiber network communication algorithm and ModelScope large model to model inference on real-time video data. The actual data results show that the StreamYOLO (Stream You Only Look Once) model can use the Streaming Perception method to detect and continuously track target vehicles in real-time videos. Finally, the method proposed in this article was experimentally validated in an actual smart highway digital infrastructure construction project. The experimental results demonstrate the high application value and promotion prospects of the fiber optic network in the division of over the horizon perception distance in intelligent roadways construction.

Background The main active ingredients of Mentha haplocalyx Briq. essential oils are monoterpenes. According to the component of essential oils, M. haplocalyx can be divided into different chemotypes. Chemotype variation is widespread in Mentha plants but its formation mechanism is unclear. Methods We selected the stable chemotype l-menthol, pulegone, and carvone of M. haplocalyx for transcriptome sequencing. To further investigate the variation of chemotypes, we analyzed the correlation between differential transcription factors (TFs) and key enzymes. Results Fourteen unigenes related to monoterpenoid biosynthesis were identified, among which (+)-pulegone reductase (PR) and (−)-menthol dehydrogenase (MD) were significantly upregulated in l-menthol chemotype and (−)-limonene 6-hydroxylase was significantly upregulated in carvone chemotype. In addition, 2,599 TFs from 66 families were identified from transcriptome data and the differential TFs included 113 TFs from 34 families. The families of bHLH, bZIP, AP2/ERF, MYB, and WRKY were highly correlated with the key enzymes PR, MD, and (−)-limonene 3-hydroxylase (L3OH) in different M. haplocalyx chemotypes (r > 0.85). The results indicate that these TFs regulate the variation of different chemotypes by regulating the expression patterns of PR, MD, and L3OH. The results of this study provide a basis for revealing the molecular mechanism of the formation of different chemotypes and offer strategies for effective breeding and metabolic engineering of different chemotypes in M. haplocalyx.

The impact of sleep deprivation on working memory can only be reversed by recovery sleep (RS). However, there are limited electrophysiological studies on the effect of RS on the improvement in working memory after sleep deprivation, and the changes in the early components of event-related potentials (ERPs) before and after RS are still unclear. Therefore, this study aims to explore the effects of RS on the earlier ERP components related to object working memory following 36 h of total sleep deprivation (TSD). Twenty healthy male participants performed an object working memory task after 36 h of TSD and after 8 h of RS. Electroencephalogram data were recorded accordingly while the task was performed. Repeated ANOVA showed that P2 amplitudes related to object working memory decreased significantly after 8 h of RS compared to after a 36 h period of TSD, but there was no significant difference from baseline (BS), which indicates a trend of recovery to the baseline state. An 8 h RS can partially improve impaired object working memory caused by TSD. However, a longer period of RS is needed for the complete recovery of cognitive function after a long period of TSD.