KK-LC-1, a biomarker for prognosis of immunotherapy for primary liver cancer.

PURPOSE: There is mounting evidence that patients with liver cancer can benefit from Immune checkpoint inhibitors. However, due to the high cost and low efficacy, we aimed to explore new biomarkers for predicting the efficacy of immunotherapy. METHODS: Specimens and medical records of liver cancer patients treated at Drum Tower Hospital of Nanjing University were collected, and the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in tissues as well as the corresponding antibodies in serum were examined to find biomarkers related to the prognosis of immunotherapy and to explore its mechanism in the development of liver cancer. RESULTS: KK-LC-1 expression was found to be 34.4% in histopathological specimens from 131 patients and was significantly correlated with Foxp3 expression (P = 0.0356). The expression of Foxp3 in the tissues of 24 patients who received immunotherapy was significantly correlated with overall survival (OS) (P = 0.0247), and there was also a tendency for prolonged OS in patients with high expression of KK-LC-1. In addition, the expression of KK-LC-1 antibody in the serum of patients who received immunotherapy with a first efficacy evaluation of stable disease (SD) was significantly higher than those with partial response (PR) (P = 0.0413). CONCLUSIONS: Expression of KK-LC-1 in both tissues and serum has been shown to correlate with the prognosis of patients treated with immunotherapy, and KK-LC-1 is a potential therapeutic target for oncological immunotherapy.

DLP Fabrication of Multiple Hierarchical Biomimetic GelMA/SilMA/HAp Scaffolds for Enhancing Bone Regeneration.

Severe bone defects resulting from trauma and diseases remain a persistent clinical challenge. In this study, a hierarchical biomimetic microporous hydrogel composite scaffold was constructed by mimicking the hierarchical structure of bone. Initially, gelatin methacrylamide (GelMA) and methacrylic anhydride silk fibroin (SilMA) were synthesized, and GelMA/SilMA inks with suitable rheological and mechanical properties were prepared. Biomimetic micropores were then generated by using an aqueous two-phase emulsification method. Subsequently, biomimetic microporous GelMA/SilMA was mixed with hydroxyapatite (HAp) to prepare biomimetic microporous GelMA/SilMA/HAp ink. Hierarchical biomimetic microporous GelMA/SilMA/HAp (M-GSH) scaffolds were then fabricated through digital light processing (DLP) 3D printing. Finally, in vitro experiments were conducted to investigate cell adhesion, proliferation, and inward migration as well as osteogenic differentiation and vascular regeneration effects. In vivo experiments indicated that the biomimetic microporous scaffold significantly promoted tissue integration and bone regeneration after 12 weeks of implantation, achieving 42.39% bone volume fraction regeneration. In summary, this hierarchical biomimetic microporous scaffold provides a promising strategy for the repair and treatment of bone defects.

Synthesis and Self-Assembly of Ultrathin Holey Graphdiyne Nanosheets for Oxygen Reduction Reaction.

Graphdiyne (GDY) is a fascinating graphene-like 2D carbon allotrope comprising sp and sp2 hybridized carbon atoms. However, GDY materials synthesized by solution-phase methods normally come as thick and porous films or amorphous powders with severely disordered stacking modes that obstruct macroscopic applications. Here, a facile and scalable synthesis of ultrathin holey graphdiyne (HGDY) nanosheets is reported via palladium/copper co-catalyzed homocoupling of 1,3,5-triethynylbenzene. The resulting freestanding 2D HGDY self-assembles into 3D foam-like networks which can in situ anchor clusters of palladium atoms on their surfaces. The Pd/HGDY hybrids exhibit high electrocatalytic activity and stability for the oxygen reduction reaction which outperforms that of Pt/C benchmark. Based on the ultrathin graphene-like sheets and their unique 3D interconnected macrostructures, Pd/HGDY holds great promise for practical electrochemical catalysis and energy-related applications.

Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma.

BACKGROUND: Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies. METHODS: A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan-Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM. RESULTS: The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25-5.29, p = 0.01; HR = 2.77, 95% CI 1.22-6.28, p = 0.02; HR = 3.43, 95% CI 1.51-7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17-0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38-9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20-0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients. CONCLUSIONS: Our study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.

Arsenic shapes the microbial community structures in tungsten mine waste rocks.

Tungsten (W) is a critical material that is widely used in military applications, electronics, lighting technology, power engineering and the automotive and aerospace industries. In recent decades, overexploitation of W has generated large amounts of mine waste rocks, which generate elevated content of toxic elements and cause serious adverse effects on ecosystems and public health. Microorganisms are considered important players in toxic element migrations from waste rocks. However, the understanding of how the microbial community structure varies in W mine waste rocks and its key driving factors is still unknown. In this study, high-throughput sequencing methods were used to determine the microbial community profiles along a W content gradient in W mine waste rocks. We found that the microbial community structures showed clear differences across the different W levels in waste rocks. Notably, arsenic (As), instead of W and nutrients, was identified as the most important predictor influencing microbial diversity. Furthermore, our results also showed that As is the most important environmental factor that regulates the distribution patterns of ecological clusters and keystone ASVs. Importantly, we found that the dominant genera have been regulated by As and were widely involved in As biogeochemical cycling in waste rocks. Taken together, our results have provided useful information about the response of microbial communities to W mine waste rocks.

Alveolar bone remodelling and stability of mandibular incisors in adult patients after orthodontic treatment with premolar extractions: A prospective follow-up study.

OBJECTIVE: To evaluate alveolar bone remodelling and stability of mandibular incisors in adult orthodontic extraction patients. MATERIALS AND METHODS: Cone-beam computed tomography images of 25 adult patients undergoing extraction were collected before orthodontic treatment (T1), after orthodontic treatment (T2), and after at least 1 year of retention (T3). The labial and lingual alveolar bone heights (ABH), thickness (ABT), and tooth movement of the mandibular incisors were measured during the retraction (T2-T1) and retention (T3-T2) periods. According to the tooth movement during the retention period, the mandibular incisors were further divided into stable and unstable groups, and the correlation between L1-BMe and stability was evaluated. RESULTS: The labial and lingual ABHs significantly increased after orthodontic treatment and decreased during the retention period. The lingual ABH was 7.36 ± 2.27 mm at T2 and 5.37 ± 1.98 mm at T3, indicating a great bone remodelling capacity. The labial ABT exhibited a significant increase during orthodontic treatment and a slight decrease during the retention period, while the lingual ABT showed an opposite trend. During the retention period, the root apex moved labially into the alveolar bone housing. L1-BMe significantly increased during orthodontic treatment and decreased during the retention period. Compared to the stable group, lingual ABH and L1-BMe at T2 was significantly higher, and lingual ABT was smaller in the unstable group. CONCLUSION: Post-treatment lingual alveolar bone defects of the mandibular incisors could recover to some extent during the retention period. There was a negative correlation between post-treatment L1-BMe and mandibular incisor stability.

Development and validation of the prediction model for mortality in patients with diabetic kidney disease in intensive care unit: a study based on medical information Mart for intensive care.

We aimed to explore factors associated with mortality of diabetic kidney disease (DKD), and to establish a prediction model for predicting the mortality of DKD. This was a cohort study. In total, 1,357 DKD patients were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with 505 DKD patients being identified from the MIMIC-III as the testing set. The outcome of the study was 1-year mortality. COX proportional hazard models were applied to screen the predictive factors. The prediction model was conducted based on the predictive factors. A receiver operating characteristic (ROC) curve with the area under the curve (AUC) was calculated to evaluate the performance of the prediction model. The median follow-up time was 365.00 (54.50,365.00) days, and 586 patients (43.18%) died within 1 year. The predictive factors for 1-year mortality in DKD included age, weight, sepsis, heart rate, temperature, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA), lymphocytes, red cell distribution width (RDW), serum albumin, and metformin. The AUC of the prediction model for predicting 1-year mortality in the training set was 0.771 [95% confidence interval (CI): 0.746-0.795] and the AUC of the prediction model in the testing set was 0.795 (95% CI: 0.756-0.834). This study establishes a prediction model for predicting mortality of DKD, providing a basis for clinical intervention and decision-making in time.

Protein Kinase C Lambda Mediates Acid-Sensing Ion Channel 1a-Dependent Cortical Synaptic Plasticity and Pain Hypersensitivity.

Chronic pain is a serious debilitating disease for which effective treatment is still lacking. Acid-sensing ion channel 1a (ASIC1a) has been implicated in nociceptive processing at both peripheral and spinal neurons. However, whether ASIC1a also contributes to pain perception at the supraspinal level remains elusive. Here, we report that ASIC1a in ACC is required for thermal and mechanical hypersensitivity associated with chronic pain. ACC-specific genetic deletion or pharmacological blockade of ASIC1a reduced the probability of cortical LTP induction and attenuated inflammatory thermal hyperalgesia and mechanical allodynia in male mice. Using cell type-specific manipulations, we demonstrate that ASIC1a in excitatory neurons of ACC is a major player in cortical LTP and pain behavior. Mechanistically, we show that ASIC1a tuned pain-related cortical plasticity through protein kinase C λ-mediated increase of membrane trafficking of AMPAR subunit GluA1 in ACC. Importantly, postapplication of ASIC1a inhibitors in ACC reversed previously established nociceptive hypersensitivity in both chronic inflammatory pain and neuropathic pain models. These results suggest that ASIC1a critically contributes to a higher level of pain processing through synaptic potentiation in ACC, which may serve as a promising analgesic target for treatment of chronic pain.SIGNIFICANCE STATEMENT Chronic pain is a debilitating disease that still lacks effective therapy. Ion channels are good candidates for developing new analgesics. Here, we provide several lines of evidence to support an important role of cortically located ASIC1a channel in pain hypersensitivity through promoting long-term synaptic potentiation in the ACC. Our results indicate a promising translational potential of targeting ASIC1a to treat chronic pain.

Circular RNA La-related RNA-binding protein 4 correlates with reduced tumor stage, as well as better prognosis, and promotes chemosensitivity to doxorubicin in breast cancer.

OBJECTIVE: We aimed to evaluate the correlation of circular RNA La-related RNA-binding protein 4 (circ-LARP4) with tumor characteristics and prognosis, and its effect on chemosensitivity in breast cancer. METHODS: Circ-LARP4 from tumor and adjacent tissues of 283 female breast cancer patients underwent resection was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor features, disease-free survival (DFS), and overall survival (OS) were recorded. In vitro, circ-LARP4 in human normal mammary epithelial cells (HMEC) and breast cancer cell lines was detected by RT-qPCR. MCF-7 and MDA-MB-231 cells were transfected with circ-LARP4 overexpression plasmid (as OE-Circ group) and control overexpression plasmid (as OE-Control group). Relative cell viability under different concentrations of doxorubicin was measured. RESULTS: Circ-LARP4 was decreased in tumor tissues than adjacent tissues (P < .001). Tumor circ-LARP4 negatively correlated with tumor size (P = .001), T stage (P = .009), N stage (P = .006), and TNM stage (P < .001), whereas positively correlated with DFS (P = .004) and OS (P < .001). In vitro, circ-LARP4 was decreased MCF-7, BT474, MDA-MB-231, and MDA-MB-468 cell lines than HMEC (all P < .001). Relatively cell viability of MCF-7 cells (at 20 nmol/L [P < .05], 40 nmol/L [P < .01], 80 nmol/L [P < .05] of doxorubicin) and MDA-MB-231 cells (at 120 nmol/L [P < .05], 240 nmol/L [P < .05] of doxorubicin) was decreased in OE-Circ group than OE-Control group. IC50 value of doxorubicin was decreased in OE-Circ group than OE-Control group in MCF-7 and MDA-MB-231 cell lines (both P < .01). CONCLUSION: Circ-LARP4 was a potential prognostic biomarker, which might improve the management of breast cancer.

Peripheral blood cell count ratios are predictive biomarkers of clinical response and prognosis for non-surgical esophageal squamous cell carcinoma patients treated with radiotherapy.

BACKGROUND: Peripheral blood cell count ratios, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been reported to be prognostic factors in many malignancies as markers of inflammation and immune status. The aim of this study was to determine whether NLR, PLR, or LMR can be clinical response and prognostic biomarkers of non-surgical esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy. METHODS: 193 non-surgical ESCC patients who underwent radiotherapy were retrospectively analyzed. The peripheral blood cell count ratios were obtained before, during (weekly) and at the end of the treatment. Then, we compared the subsequent results with the corresponding pretreatment values and computed the rates of change, which were defined as cNLR, cPLR, and cLMR. Univariate and multivariate Cox regression analyses were used for overall survival (OS). Ordinal logistic regression was used to analyze the clinical response. RESULTS: In multivariate analysis, cNLR at week 4(P = .026) and week 5(P = .025) during radiotherapy were significantly associated with OS, along with BMI, tumor stage, tumor length, tumor location, and grade of adverse events. Besides, BMI, tumor stage, tumor length, adverse event grade, cNLR at week 4(P = .044) and week 5(P = .013), and cPLR at week 4(P = .034) and week 5(P = .015) were significantly associated with the clinical response in the multivariate logistic regression analysis. CONCLUSIONS: The cNLR at weeks 4 and 5 was negatively correlated with the OS and clinical response of non-surgical ESCC patients treated with radiotherapy. The elevated cPLR at weeks 4 and 5 was only related to poor clinical response.

Association between sarcopenic obesity and mortality in patients on peritoneal dialysis: a prospective cohort study.

Background: Whether sarcopenic obesity had unfavorable effect on survival of peritoneal dialysis (PD) patients is unknown. We aimed to investigate the association between sarcopenic obesity and survival in PD patients. Methods: This was a prospective observational study. Eligible PD patients from November 2016 to December 2017 were enrolled and followed until August 31, 2023. Sarcopenia was defined following the recommendations of the Asian Working Group for Sarcopenia (AWGS) as low appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Obesity was defined using the percentage of body fat (PBF). Survival analysis was conducted using the Kaplan-Meier and log-rank test. The Cox regression and the cumulative incidence competing risk (CICR) analyzes were used to investigate the association between sarcopenic obesity and all-cause mortality. Results: A total of 223 patients were enrolled with 133 (59.6%) males, a median age of 57.5 (44.6, 65.7) years, a median dialysis vintage of 20.3 (6.4, 57.7) months and 48 (21.5%) who had comorbid diabetes mellitus. Among them, 46 (20.6%) patients were sarcopenic, and 25 (11.2%) patients were diagnosed with sarcopenic obesity. After followed up for 51.6 (25.6, 73.9) months, the Kaplan-Meier curve showed the sarcopenic obesity (log-rank = 13.527, p < 0.001) group had significant lower survival rate compared to the nonsarcopenic non-obesity group. For multivariate analysis, the CICR method showed patients with sarcopenic obesity had significantly higher mortality rate (HR: 2.190, 95% CI: 1.011-4.743, p = 0.047) compared to those with nonsarcopenic non-obesity. Conclusion: Sarcopenia is not uncommon in PD patients, with a considerable proportion having sarcopenic obesity. There is a significant association between sarcopenic obesity and an increased risk of mortality in PD patients.

Trauma plays an important role in acral melanoma: A retrospective study of 303 patients.

INTRODUCTION: Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. METHODS: A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. RESULTS: Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. CONCLUSION: This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

Single-arm study of camrelizumab plus apatinib for patients with advanced mucosal melanoma.

BACKGROUND: Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers. METHODS: We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR). RESULTS: Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response. CONCLUSION: Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023277.

Adjuvant chemotherapy for pT1-3N0-1 breast cancer patients with HR+, HER2- subtype: a propensity-score matched study with competing risk analysis.

OBJECTIVE: To wholly evaluate the prognostic value of CHT for pT1-3N0-1 breast cancer patients with HR+, HER2- subtype using the Surveillance, Epidemiology, and End Results (SEER) database. METHOD: A total of 126,102 eligible cases diagnosed between January 2010 and December 2018 were included in the SEER database. A propensity-score matched (PSM) study with competing risk analysis was conducted. The Kaplan-Meier method was used to visualize the survival disparities between chemotherapy (CHT) and no CHT groups. The cumulative incidences of different subgroups were compared by Fine-Gray's test. RESULTS: Before PSM, patients in the CHT group had worse OS and CSS (both P < 0.001). After PSM, we were surprised that patients in the CHT group had a better OS than those in the no CHT group (HR 0.74, 95% CI 0.68-0.80, P < 0.001), while no significant survival disparities were observed for CSS (HR 1.00, 95% CI 0.89-1.12, P = 0.952). In the competing risk analysis, the OS disparities between the CHT and no CHT groups were mainly attributed to deaths of other causes (subdistribution HR [95% CI] 0.50 [0.44-0.57]). After adjusting for other competitive risk events, there was no significant difference in cumulative death risk of breast cancer between the CHT and no CHT groups (subdistribution HR [95% CI] 1.01 [0.90-0.1.13]). CONCLUSION: The present study is the first, to our knowledge, to wholly evaluate the prognostic value of CHT for pT1-3N0-1 breast cancer patients with HR+, HER2- subtype using a propensity-score matched study with competing risk analysis. All pT1-3N0-1 breast cancer patients with HR+, HER2- subtype do not benefit from CHT. Genetic testing may be the only effective tool to determine the need for CHT at the present.

Necroptosis Related Genes Predict Prognosis and Therapeutic Potential in Gastric Cancer.

The clinical significance of necroptosis in gastric cancer (GC) has yet to be fully elucidated. The purpose of our study was to identify a necroptosis-relevant gene and to establish a prediction model to estimate the prognosis and therapeutic potential in GC. Here, we explored the expression profile of 76 necroptosis-related genes in TCGA-STAD patients. A six-gene risk score prediction model was established via regression analysis of the least absolute shrinkage and selection operator (LASSO) and validated in a separate cohort. Patients were separated into low- or high-risk groups according to the median risk score. We then compared and analyzed the biological process characteristics of two risk groups. Additionally, cell-to-cell communications and metabolic activity were analyzed in a single-cell solution. The in vitro experiments were conducted to explore the biological functions and drug sensitivity of necroptosis-related genes in gastric cancer. Our results identified that compared with the low-risk group, the high-risk group was associated with a higher clinical stage or grade and a worse prognosis. In addition, the low-risk group had higher levels of immunity and immune cell infiltration. Necroptosis was triggered by the TNF pathway in myeloid cells and the glycolysis pathway was altered. Necroptosis-related genes modulated the cell function, including proliferation and migration in vitro. Furthermore, the potential drugs' sensitivity was higher in the low-risk subgroup. These findings could facilitate a better understanding and improve the treatment potential and prognosis of GC patients.

Light response of gametophyte in Adiantum flabellulatum: transcriptome analysis and identification of key genes and pathways.

Light serves not only as a signaling cue perceived by plant photoreceptors but also as an essential energy source captured by chloroplasts. However, excessive light can impose stress on plants. Fern gametophytes possess the unique ability to survive independently and play a critical role in the alternation of generations. Due to their predominantly shaded distribution under canopies, light availability becomes a limiting factor for gametophyte survival, making it imperative to investigate their response to light. Previous research on fern gametophytes' light response has been limited to the physiological level. In this study, we examined the light response of Adiantum flabellulatum gametophytes under different photosynthetic photon flux density (PPFD) levels and identified their high sensitivity to low light. We thereby determined optimal and stress-inducing light conditions. By employing transcriptome sequencing, weighted gene co-expression network analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, we identified 10,995 differentially expressed genes (DEGs). Notably, 3 PHYBs and 5 Type 1 CRYs (CRY1s) were significantly down-regulated at low PPFD (0.1 µmol m-2 s-1). Furthermore, we annotated 927 DEGs to pathways related to photosynthesis and 210 to the flavonoid biosynthesis pathway involved in photoprotection. Additionally, we predicted 34 transcription factor families and identified a close correlation between mTERFs and photosynthesis, as well as a strong co-expression relationship between MYBs and bHLHs and genes encoding flavonoid synthesis enzymes. This comprehensive analysis enhances our understanding of the light response of fern gametophytes and provides novel insights into the mechanisms governing their responses to light.

Role of vascular endothelial growth factor in radiotherapy resistance to esophageal squamous cell carcinoma.

Vascular endothelial growth factor (VEGF) is related to the radiation resistance of tumors, resulting in the failure of tumor radiotherapy. The purpose of this study was to discuss the role of VEGF in radiotherapy resistance of esophageal squamous cell carcinoma (ESCC). We used the VEGF kit by ELISA to detect the serum VEGF level of ESCC patients who only received radiotherapy. The expression of VEGF in ESCC cells after siRNA treatment was verified by Western blot. The sensitivity of ESCC cells to radiation after knocking down VEGF was analyzed by Clonogenic assay and Cell counting kit (CCK-8). The results showed that the level of serum VEGF in patients with ESCC before and after radiotherapy was related to the clinical response, and it was confirmed that knocking down the expression of VEGF in ESCC cells improved the sensitivity to radiation.

Evaluation of measurement accuracy of wearable devices for heart rate variability.

This paper proposed a method based on heart rate variability (HRV) for evaluating the accuracy of wearable devices in measuring heart rate. HRV refers to the variation in time intervals between successive heartbeats, widely used in many fields such as clinical and sports fields. Wearable devices such as Electrocardiogram (ECG) electrode patches have gained popularity due to their portability and ease of use. However, they can be prone to measurement interference caused by environmental noise, human respiration, etc. The proposed method consists of four main components: selection of "gold standard measurement devices", identification of HRV measurement metrics, construction of an HRV evaluation framework, and quantification of measurement errors. The method is validated through simulated experiments using ECG patches. The evaluation framework and quantification model established in this method have significant implications in establishment of industry standards and diagnosis of diseases in clinical practice.

Two-Dimensional Atomically Thin Titanium Nitride via Topochemical Conversion.

Titanium nitride as a typical transition metal nitride (TMN) has attracted increasing interest for its fascinating characteristics and widespread applications. However, the synthesis of two-dimensional (2D) atomically thin titanium nitride is still challenging which hinders its further research in electronic and optoelectronic fields. Here, 2D titanium nitride with a large area was prepared via in situ topochemical conversion of the titanate monolayer. The titanium nitride reveals a thickness-dependent metallic-to-semiconducting transition, where the atomically thin titanium nitride with a thickness of ∼1 nm exhibits an n-type semiconducting behavior and a highly sensitive photoresponse and displays photoswitchable resistance by repeated light irradiation. First-principles calculations confirm that the chemisorbed oxygen on the surface of the titanium nitride nanosheet depletes its electrons, while the light irradiation induced desorption of oxygen leads to increased electron doping and hence the conductance of titanium nitride. These results may allow the scalable synthesis of ultrathin TMNs and facilitate their fundamental physics research and next-generation optoelectronic applications.

Representation and control of pain and itch by distinct prefrontal neural ensembles.

Pain and itch are two closely related but essentially distinct sensations that elicit different behavioral responses. However, it remains mysterious how pain and itch information is encoded in the brain to produce differential perceptions. Here, we report that nociceptive and pruriceptive signals are separately represented and processed by distinct neural ensembles in the prelimbic (PL) subdivision of the medial prefrontal cortex (mPFC) in mice. Pain- and itch-responsive cortical neural ensembles were found to significantly differ in electrophysiological properties, input-output connectivity profiles, and activity patterns to nociceptive or pruriceptive stimuli. Moreover, these two groups of cortical neural ensembles oppositely modulate pain- or itch-related sensory and emotional behaviors through their preferential projections to specific downstream regions such as the mediodorsal thalamus (MD) and basolateral amygdala (BLA). These findings uncover separate representations of pain and itch by distinct prefrontal neural ensembles and provide a new framework for understanding somatosensory information processing in the brain.