Multiscale Characterization and Biomimetic Design of Porcupine Quills for Enhanced Mechanical Performance.

The mechanical properties of porcupine quills have attracted the interest of researchers due to their unique structure and composition. However, there is still a knowledge gap in understanding how these properties can be utilized to design biomimetic structures with enhanced performance. This study delves into the nanomechanical and macro-mechanical properties of porcupine quills, unveiling varied elastic moduli across different regions and cross sections. The results indicated that the elastic moduli of the upper and lower epidermis were higher at 8.13 ± 0.05 GPa and 7.71 ± 0.14 GPa, respectively, compared to other regions. In contrast, the elastic modulus of the mid-dermis of the quill mid-section was measured to be 7.16 ± 0.10 GPa. Based on the micro- and macro-structural analysis of porcupine quills, which revealed distinct variations in elastic moduli across different regions and cross sections, various biomimetic porous structures (BPSs) were designed. These BPSs were inspired by the unique properties of the quills and aimed to replicate and enhance their mechanical characteristics in engineering applications. Compression, torsion, and impact tests illustrated the efficacy of structures with filled hexagons and circles in improving performance. This study showed enhancements in maximum torsional load and crashworthiness with an increase in filled structures. Particularly noteworthy was the biomimetic porous circular structure 3 (BPCS_3), which displayed exceptional achievements in average energy absorption (28.37 J) and specific energy absorption (919.82 J/kg). Finally, a response surface-based optimization method is proposed to enhance the design of the structure under combined compression-torsion loads, with the goal of reducing mass and deformation. This research contributes to the field of biomimetics by exploring the potential applications of porcupine quill-inspired structures in fields such as robotics, drive shafts, and aerospace engineering.

Production of Margarine Fat Containing Medium- and Long-Chain Triacylglycerols by Enzymatic Interesterification of Peony Seed Oil, Palm Stearin and Coconut Oil Blends.

This paper reports the preparation of margarine fat using Lipozyme TL IM as a catalyst and peony seed oil (PSO), palm stearin (PS) and coconut oil (CO) as raw materials. The results indicate that there were no significant changes in fatty acid composition before or after interesterification of the oil samples. However, the total amount of medium- and long-chain triglycerides (MLCTs) increased from 2.92% to 11.38% in sample E1 after interesterification, mainly including LaLaO, LaMO, LaPM, LaOO, LaPO and LaPP. Moreover, the slip melting point (SMP) of sample E1 decreased from 45.9 °C (B1) to 33.5 °C. The solid fat content (SFC) of all the samples at 20 °C was greater than 10%, indicating that they could effectively prevent oil exudation. After interesterification, the samples exhibited a ß' crystal form and could be used to prepare functional margarine.

Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy.

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

Childhood maltreatment, shame, and self-esteem: an exploratory analysis of influencing factors on criminal behavior in juvenile female offenders.

OBJECTIVE: This study aimed to investigate the relationships between childhood maltreatment, shame, and self-esteem among juvenile female offenders and to explore the potential influencing factors on their criminal behavior. METHODS: Using a stratified cluster sampling method, 1,227 juvenile female offenders from 11 provinces in China were surveyed using the Childhood Trauma Questionnaire (CTQ), Self-Esteem Scale (SES), and a self-developed Shame Questionnaire for Juvenile Offenders. Data were analyzed using descriptive statistics, correlation analysis, chi-square tests, t-tests, and structural equation modeling with mediation analysis. RESULTS: (1) Childhood maltreatment have a significant potential influencing factors on criminal behavior; (2) Childhood maltreatment was positively correlated with self-esteem(ß = 0.351, p < 0.001); (3) shame (ß = 0.042, p < 0.001) mediate the relationship between Childhood maltreatment and self-esteem (childhood maltreatment → shame → self-esteem (95% Cl: 0.033, 0.052)). CONCLUSION: This study demonstrates that childhood maltreatment is a significant predictor of criminal behavior among juvenile female offenders. childhood maltreatment can directly influence of self-esteem, which can also affect juvenile female offenders'self-esteem indirectly through shame. The findings suggest that shame are important variables that mediate the effect of the juvenile female offenders'childhood maltreatment on their self-esteem.

The clinical and pathological features of Kimura disease in pediatric patients.

Background: Kimura disease is characterized by inflammation, with its underlying causes remaining uncertain. There is a lack of comprehensive and systematic research on the pathology of this condition in pediatric patients. Our objective is to study the clinical and pathological attributes of Kimura disease in pediatric patients and investigate the potential diagnostic significance of immunoglobulin E (IgE) in this context. Methods: Clinical and laboratory information, pathological characteristics, and follow-up data were correlated to examine the distinctive features. Immunohistochemistry, acid-fast staining, and molecular assay were used to identify the presence of IgE and pathogens. Results: We conducted an analysis of five cases of Kimura disease in pediatric patients at our hospital. The patients' ages ranged from 5 years and 7 months to 14 years and 2 months, with 4 (80%) being male. The most common site was the head and neck region, particularly the postauricular subcutaneous area. Eosinophilia was observed in four patients (80%), and two patients (40%) had elevated serum immunoglobulin E (IgE) levels. Histopathological changes included eosinophilic infiltrates, follicular hyperplasia, and the proliferation of postcapillary venules. Immunohistochemical results supported the reactive nature of the lymphoid process and IgE deposition in the follicle, while no specific pathogens were discovered by special staining. All patients underwent surgical excision, and none experienced recurrence in their original location. Conclusion: Children with Kimura disease show distinct eosinophilic and IgE alterations in both laboratory findings and pathological features. The application of immunohistochemical staining of IgE could serve as a promising marker for diagnosing Kimura disease.

Research on consumers' purchase intention of cultural and creative products-Metaphor design based on traditional cultural symbols.

Chinese traditional cultural symbols possess great aesthetic and cultural value, and are widely utilized in product design. In this study, we explore the relationship between metaphor design based on traditional cultural symbols, customer experience and cultural identity, and further estimate how these three variables stimulate consumers' perceived value to generate consumers' purchase intention. Based on existing traditional cultural literature and Stimulus-organism-response theory (SOR), we proposed a theoretical research model to characterize the relationship among metaphor design based on traditional cultural symbols, customer experience, cultural identity, perceived value and consumers' purchase intention. A research survey was conducted and 262 questionnaires were collected in total with 241 valid. We used Smart PLS graph version 3.0 for data analysis. Results indicate that the cognition of metaphor design based on traditional cultural symbols and customer experience has a direct and significant impact on the emotional value thereby, eliciting consumers' purchase intention, metaphor design based on traditional cultural symbols is directly and indirectly (i.e., through customer experience or perceived value) positively associated with consumers' purchase intention, also customer experience is directly and indirectly (i.e., through perceived value) associated with consumer purchase intention, cultural identity mediates the indirect effect of customer experience and perceived value on purchase intention, the moderating role of cultural identity between customer experience and perceived value is not significant. Our findings help to expand the existing literature on consumer purchase intentions by rationally using traditional cultural symbols in the product metaphor design.

Rational Design of Nitride Phosphor-In-Glass with Robust Stability and Photoluminescence Performance.

Phosphor-in-glass represents a promising avenue for merging the luminous efficiency of high-quality phosphor and the thermal stability of a glass matrix. Undoubtedly, the glass matrix system and its preparation are pivotal factors in achieving high stability and preserving the original performance of embedded phosphor particles. In contrast to the well-established commercial Y3Al5O12:Ce3+ oxide phosphor, red nitride phosphor, which plays a critical role in high-quality lighting, exhibits greater structural instability during the high-temperature synthesis of inorganic glasses. A telluride glass with a refractive index (RI = 2.15@615 nm) akin to that of nitride phosphor (∼2.19) has been devised, demonstrating high efficiency in photon utilization. The lower glass-transition temperature plays a crucial role in safeguarding phosphor particles against erosion resulting from exposure to high-temperature melts. Phosphor-in-glass retains 93% of the quantum efficiency observed for pure phosphor. The assembled white light-emitting diodes module has precise color tuning capabilities, achieving an optimal color rendering index of 93.7, a luminous efficacy of 80.4 lm/W, and a correlated color temperature of 5850 K. These outcomes hold potential for advancing the realm of inorganic package and high-quality white light illumination.

The relationship between social withdrawal and problematic social media use in Chinese college students: a chain mediation of alexithymia and negative body image.

This study explores the relationship between social withdrawal and problematic social media use among college students, with a focus on the mediating roles of alexithymia and negative body image. Using the University Student Social Withdrawal Questionnaire, Social Media Addiction Scale, Toronto Alexithymia Scale, and Negative Body Image Scale, 2582 college students (33.46% male, average age = 19.46 years, SD = 2.23) were surveyed. Social withdrawal, alexithymia, negative body image, and problematic social media use were significantly correlated with each other. Social withdrawal positively predicted problematic social media use, and both alexithymia and negative body image played a chain mediating role between social withdrawal and problematic social media use. The findings indicate that individual social withdrawal is associated with college students' problematic use of social media. The results suggest that alexithymia and negative body image may mediate this association, highlighting a potential pathway through which social withdrawal influences social media use patterns.

A multicenter proof-of-concept study on deep learning-based intraoperative discrimination of primary central nervous system lymphoma.

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.

1D-CNN-based audio tampering detection using ENF signals.

The extensive adoption of digital audio recording has revolutionized its application in digital forensics, particularly in civil litigation and criminal prosecution. Electric network frequency (ENF) has emerged as a reliable technique in the field of audio forensics. However, the absence of comprehensive ENF reference datasets limits current ENF-based methods. To address this, this study introduces ATD, a blind audio forensics framework based on a one-dimensional convolutional neural network (1D-CNN) model. ATD can identify phase mutations and waveform discontinuities within the tampered ENF signal, without relying on an ENF reference database. To enhance feature extraction, the framework incorporates characteristics of the fundamental harmonics of ENF signals. In addition, a denoising method termed ENF noise reduction (ENR) based on the variational mode decomposition (VMD) and robust filtering algorithm (RFA) is proposed to reduce the impact of external noise on embedded electric network frequency signals. This study investigates three distinct types of audio tampering-deletion, insertion, and replacement-culminating in the design of binary-class tampering detection scenarios and four-class tampering detection scenarios tailored to these tampering types. ATD achieves a tampering detection accuracy of over 93% in the four-class scenario and exceeds 96% in the binary-class scenario. The effectiveness, efficiency, adaptability, and robustness of ATD in the two and four classification scenarios have been confirmed by extensive experiments.

A multi-parametric prognostic model based on clinicopathologic features: vessels encapsulating tumor clusters and hepatic plates predict overall survival in hepatocellular carcinoma patients.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) is a newly described vascular pattern that is distinct from microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Despite its importance, the current pathological diagnosis report does not include information on VETC and hepatic plates (HP). We aimed to evaluate the prognostic value of integrating VETC and HP (VETC-HP model) in the assessment of HCC. METHODS: A total of 1255 HCC patients who underwent radical surgery were classified into training (879 patients) and validation (376 patients) cohorts. Additionally, 37 patients treated with lenvatinib were studied, included 31 patients in high-risk group and 6 patients in low-risk group. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to establish a prognostic model for the training set. Harrell's concordance index (C-index), time-dependent receiver operating characteristics curve (tdROC), and decision curve analysis were utilized to evaluate our model's performance by comparing it to traditional tumor node metastasis (TNM) staging for individualized prognosis. RESULTS: A prognostic model, VETC-HP model, based on risk scores for overall survival (OS) was established. The VETC-HP model demonstrated robust performance, with area under the curve (AUC) values of 0.832 and 0.780 for predicting 3- and 5-year OS in the training cohort, and 0.805 and 0.750 in the validation cohort, respectively. The model showed superior prediction accuracy and discrimination power compared to TNM staging, with C-index values of 0.753 and 0.672 for OS and disease-free survival (DFS) in the training cohort, and 0.728 and 0.615 in the validation cohort, respectively, compared to 0.626 and 0.573 for TNM staging in the training cohort, and 0.629 and 0.511 in the validation cohort. Thus, VETC-HP model had higher C-index than TNM stage system(p < 0.01).Furthermore, in the high-risk group, lenvatinib alone appeared to offer less clinical benefit but better disease-free survival time. CONCLUSIONS: The VETC-HP model enhances DFS and OS prediction in HCC compared to traditional TNM staging systems. This model enables personalized temporal survival estimation, potentially improving clinical decision-making in surveillance management and treatment strategies.

The RAS-signaling-pathway-mutation-related prognosis in B-cell acute lymphoblastic leukemia: A report from South China children's leukemia group.

The next-generation sequencing technologies application discovers novel genetic alterations frequently in pediatric acute lymphoblastic leukemia (ALL). RAS signaling pathway mutations at the time of relapse ALL frequently appear as small subclones at the time of onset, which are considered as the drivers in ALL relapse. Whether subclones alterations in the RAS signaling pathway should be considered for risk group stratification of ALL treatment is not decided yet. In this work, we investigate the RAS signaling pathway mutation spectrum and the related prognosis in pediatric ALL. We employed an NGS panel comprising 220 genes. NGS results were collected from 202 pediatric ALL patients. 155 patients (76.7%) harbored at least one mutation. The incidences of RAS signaling pathway mutations are different significantly between T-ALL and B-ALL. In B-ALL, the RAS pathway is mostly involved, and NRAS (17.6%), KRAS (22.7%), and PTPN11 (7.7%) were the three most frequently mutated genes. Co-occurring mutations of CREBBP and NRAS, FLT3, or PTPN11 (p = 0.002, p = 0.009, and p = 0.003, respectively) were found in this cohort. The 3-year RFS rates for the RAS signaling pathway mutation-positive and negative cases was 76.5 % versus 89.7 % (p = 0.012). Four cases relapsed in the lately 3 years were RAS signaling pathway mutation-positive. RAS signaling pathway mutation is an important biomarker for poorer relapse-free survival in pediatric B-ALL patients despite good early MRD levels.

The Role of Infiltrated T Lymphocyte in Oral Squamous Cell Carcinoma: Insights into Clinicopathological Characteristics and Prognosis.

Background: To compare and analyze the presence of CD4+ and CD8 + lymphocyte infiltrates in Oral squamous cell carcinoma (OSCC) tissue versus adjacent tissue and their clinical significance. Methods: We enrolled a total of 152 patients diagnosed with OSCC, all of whom had confirmed diagnoses through pathological reports. Clinical and demographics data were extracted from medical records. Tissue microarrays were constructed and immunohistochemical staining for CD4 and CD8 was performed. Findings: The average number of infiltrating CD4+ T cells in OSCC tumor tissue was 1026.22±1163.36 cells/mm2, which did not significantly differ from the count in adjacent tissue, which was 1163.36±1013.23 cells/mm2. However, the number of CD8+ T cell infiltration in tumor tissue was significantly higher than in adjacent tissue (655.25±705.70 vs 504.56±659.26 cells/mm2, p = 0.026). We observed that, among patients who consumed alcohol, the CD4+ T cell infiltration in tumor tissue being significantly lower than that in adjacent tissue (P=0.036). Moreover, the CD8+ T cell infiltration in cancer tissue was significantly higher than in adjacent tissue for T1-2 patients (p=0.005). Patients with higher CD8+ T cell in tumor tissue exhibited significantly improved overall survival (p = 0.043). Multivariate analyses revealed that alcohol consumption had a significant impact on the number of CD4+T lymphocytes in tumor tissue (OR = 0.403, P = 0.033) while T stage was the independent factor affecting CD8+ T lymphocyte infiltration in tumor tissue (OR = 0.459, P = 0.031). Interpretation: OSCC patients with a higher number of CD8+ T lymphocyte infiltration in tumor tissue exhibited an improved prognosis.

Genome-wide identification and evolutionary analysis of the NRAMP gene family in the AC genomes of Brassica species.

BACKGROUND: Brassica napus, a hybrid resulting from the crossing of Brassica rapa and Brassica oleracea, is one of the most important oil crops. Despite its significance, B. napus productivity faces substantial challenges due to heavy metal stress, especially in response to cadmium (Cd), which poses a significant threat among heavy metals. Natural resistance-associated macrophage proteins (NRAMPs) play pivotal roles in Cd uptake and transport within plants. However, our understanding of the role of BnNRAMPs in B. napus is limited. Thus, this study aimed to conduct genome-wide identification and bioinformatics analysis of three Brassica species: B. napus, B. rapa, and B. oleracea. RESULTS: A total of 37 NRAMPs were identified across the three Brassica species and classified into two distinct subfamilies based on evolutionary relationships. Conservative motif analysis revealed that motif 6 and motif 8 might significantly contribute to the differentiation between subfamily I and subfamily II within Brassica species. Evolutionary analyses and chromosome mapping revealed a reduction in the NRAMP gene family during B. napus evolutionary history, resulting in the loss of an orthologous gene derived from BoNRAMP3.2. Cis-acting element analysis suggested potential regulation of the NRAMP gene family by specific plant hormones, such as abscisic acid (ABA) and methyl jasmonate (MeJA). However, gene expression pattern analyses under hormonal or stress treatments indicated limited responsiveness of the NRAMP gene family to these treatments, warranting further experimental validation. Under Cd stress in B. napus, expression pattern analysis of the NRAMP gene family revealed a decrease in the expression levels of most BnNRAMP genes with increasing Cd concentrations. Notably, BnNRAMP5.1/5.2 exhibited a unique response pattern, being stimulated at low Cd concentrations and inhibited at high Cd concentrations, suggesting potential response mechanisms distinct from those of other NRAMP genes. CONCLUSIONS: In summary, this study indicates complex molecular dynamics within the NRAMP gene family under Cd stress, suggesting potential applications in enhancing plant resilience, particularly against Cd. The findings also offer valuable insights for further understanding the functionality and regulatory mechanisms of the NRAMP gene family.

Lowest Glucagon/Highest C-Peptide in Oral Glucose Tolerance Test: Clinical Utility in Monitoring Glucose Control in Type 2 Diabetes Mellitus.

Purpose: Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM. Patients and Methods: Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L). Results: The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = -3.71, p < 0.001). Conclusion: Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment.

Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis.

PURPOSE: Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients. METHODS: Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years. RESULTS: We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 µm compared to that of 51.7 ± 2.6 µm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels. CONCLUSIONS: Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA.

A Systematic Review of the Advances in the Study of T Lymphocyte Suppressor Receptors in HBV Infection: Potential Therapeutic Targets.

Background: HBV-specific T lymphocytes are pivotal in eliminating the hepatitis B virus (HBV) and regulating intrahepatic inflammatory reactions. Effective T cell responses curtail HBV infection; however, compromised immunity can result in persistent infection. Beyond the acute phase, the continued presence of antigens and inflammation leads to the increased expression of various inhibitory receptors, such as PD-1, CTLA-4, Tim-3, LAG3, 2B4, CD160, BTLA, and TIGIT. This escalates the dysfunction of and diminishes the immune and proliferative abilities of T cells. Methods: In this study, we reviewed English-language literature from PubMed, Web of Science, and Scopus up to 9 July 2023. This paper aims to elucidate the inhibitory effects of these receptors on HBV-specific T lymphocytes and how immune function can be rejuvenated by obstructing the inhibitory receptor signaling pathway in chronic HBV patients. We also summarize the latest insights into related anti-HBV immunotherapy. Result: From 66 reviewed reports, we deduced that immunotherapy targeting inhibitory receptors on T cells is a reliable method to rejuvenate T cell immune responses in chronic HBV patients. However, comprehensive combination therapy strategies are essential for a functional cure. Conclusions: Targeting T cell suppressor receptors and combining immunotherapy with antiviral treatments may offer a promising approach towards achieving a functional cure, urging future research to prioritize effective combination therapeutic strategies for chronic HBV infection.

Molecular Mechanisms of Sorbed Ion Effects during Boehmite Particle Aggregation.

Classical theories of particle aggregation, such as Derjaguin-Landau-Verwey-Overbeek (DLVO), do not explain recent observations of ion-specific effects or the complex concentration dependence for aggregation. Thus, here, we probe the molecular mechanisms by which selected alkali nitrate ions (Na+, K+, and NO3-) influence aggregation of the mineral boehmite (γ-AlOOH) nanoparticles. Nanoparticle aggregation was analyzed using classical molecular dynamics (CMD) simulations coupled with the metadynamics rare event approach for stoichiometric surface terminations of two boehmite crystal faces. Calculated free energy landscapes reveal how electrolyte ions alter aggregation on different crystal faces relative to pure water. Consistent with experimental observations, we find that adding an electrolyte significantly reduces the energy barrier for particle aggregation (∼3-4×). However, in this work, we show this is due to the ions disrupting interstitial water networks, and that aggregation between stoichiometric (010) basal-basal surfaces is more favorable than between (001) edge-edge surfaces (∼5-6×) due to the higher interfacial water densities on edge surfaces. The interfacial distances in the interlayer between aggregated particles with electrolytes (∼5-10 Å) are larger than those in pure water (a few Ångströms). Together, aggregation/disaggregation in salt solutions is predicted to be more reversible due to these lower energy barriers, but there is uncertainty on the magnitudes of the energies that lead to aggregation at the molecular scale. By analyzing the peak water densities of the first monolayer of interstitial water as a proxy for solvent ordering, we find that the extent of solvent ordering likely determines the structures of aggregated states as well as the energy barriers to move between them. The results suggest a path for developing a molecular-level basis to predict the synergies between ions and crystal faces that facilitate aggregation under given solution conditions. Such fundamental understanding could be applied extensively to the aggregation and precipitation utilization in the biological, pharmaceutical, materials design, environmental remediation, and geological regimes.

Depression, anxiety, and insomnia symptoms among Chinese college students: A network analysis across pandemic stages.

BACKGROUND: As the stages of the COVID-19 pandemic evolved, the symptoms of depression, anxiety, and insomnia have increasingly manifested among Chinese college students. The aim of this study is to investigate the relationships between these symptoms through network analysis among Chinese college students during COVID-19. METHOD: A three-wave cross-sectional survey was conducted at 22 colleges in Guangdong Province, involving 381,152 students during three specific time intervals: T1 (baseline, February 3 to 10, 2020), T2 (19 months after baseline, June 10 to 18, 2021), and T3 (37 months after baseline, March 15 to April 22, 2023). Depression (PHQ-9), anxiety (GAD-7), and insomnia (YSIS) were used separately. We analyzed two key network indices: "Expected influence" and "Bridge expected influence". Network stability was assessed through a case-dropping bootstrap program. RESULT: The effective sample sizes for the three periods were as follows: T1 - 164,101 (103,645 females, 63.2 %), T2 - 86,767 (52,146 females, 60.1 %), and T3 - 130,284 (76,720 females, 58.9 %). Across these three periods, the key central symptoms were "Fatigue" (PHQ4), "Restlessness" (GAD5), "Uncontrollable worrying" (GAD2), "Worry too much" (GAD3) and "Sleep insufficiency" (YSIS6). Notably, "Fatigue" (PHQ4), "Restlessness" (GAD5) and "Irritability" (GAD6) consistently served as bridge symptoms. In the T1 and T2 period, "Motor" (PHQ8) acted as a bridge symptom but weakened in T3. CONCLUSION: Throughout the three periods, the mental health issues among Chinese college students displayed characteristics of somatization within the depression-anxiety-insomnia comorbidity network. Over time, anxiety symptoms appeared to become more prominent. Consequently, this study highlights the importance of accurately identifying and promptly intervening in these core symptoms of mental health among college students, as these symptoms may evolve across different stages of a pandemic.