Spore Oil enhances the effect of cyclophosphamide inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice.

OBJECTIVE: To investigate the effect of Ganoderma Lucidum Spore Oil (GLSO) on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide (CTX), and explore the underlying mechanism. METHODS: Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals, and Kaplan-Meier survival analysis was used to analyze the life span. Plasma biochemical examination was used to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (UREA) and creatinine (CRE). Western blot analysis was performed to detect Programmed Death-1 (PD-1), Programmed Death Ligand 1 (PD-L1), Janus Kinase 2 (JAK2), phosphorylated Signal Transducer and Activator of Transcription 3 (p-STAT3), and Signal Transducer and Activator of Transcription 3 (STAT3) expression. RESULTS: GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with CTX. Meanwhile, GLSO increased the thymus index and showed no obvious toxicity to liver functions of animals. GLSO also decreased the level of UREA in H22 tumor-bearing mice treated with CTX. Furthermore, GLSO could inhibit the expression of PD-1 in spleen, which was independent of JAK2 expression and STAT3 phosphorylation. However, GLSO did not affect the expression of PD-L1, JAK2, and p-STAT3 in tumor tissue. CONCLUSION: GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumor-bearing mice, while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in spleen. Furthermore, these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.

Risk factors for acute complicated appendicitis in children aged three years and younger.

OBJECTIVE: The aim of this study is to identify risk factors associated with acute complicated appendicitis (CA) in children aged three years or younger, providing a theoretical foundation for the management and treatment of acute appendicitis (AA). METHODS: A retrospective analysis was conducted on 135 pediatric patients with AA, admitted to the Department of General Surgery at Anhui Children's Hospital between December 2020 and December 2023, who underwent successful surgical treatment. Based on the intraoperative and postoperative pathological findings, patients were categorized into two groups: complicated appendicitis (CA) (n = 97 cases) and uncomplicated appendicitis (UA) (n = 38 cases). Clinical data including gender, age, weight, disease duration, preoperative white blood cell count (WCC), neutrophil granulocyte (NEUT) count, C-reactive protein (CRP) levels, total bilirubin (TBil) levels, procalcitonin (PCT) levels, calprotectin (Cal) levels, preoperative ultrasound results indicating the presence or absence of fecaliths, maximum appendix diameter, and pediatric appendicitis sore (PAS) were collected and analyzed. Comparative analysis was performed to investigate the differences between the groups and identify risk factors of CA. RESULTS: The CA group exhibited significantly higher values in disease duration, CRP levels, PCT, Cal, presence of appendiceal fecaliths, maximum appendix diameter, and PAS compared to the UA group (P < 0.05). Multivariate analysis identified CRP levels, maximum appendix diameter, and PAS as independent risk factors for CA. Specifically, differences in CRP level (OR = 1.045, 95% CI:1.024 ~ 1.067, P < 0.001), PAS (OR = 1.768, 95% CI:1.086 ~ 2.879, P = 0.022), and maximum appendix diameter (OR = 1.860, 95% CI:1.085 ~ 3.191, P = 0.024) were significant. The area under the receiver operating characteristic curve values were 0.6776 for the PAS, 0.7663 for CRP, and 0.5604 for the maximum appendix diameter. CONCLUSION: CRP levels, PAS, and maximum appendix diameter are independent risk factors for CA in children under three years of age. These parameters are valuable for the early diagnosis of CA.

Eliminating Cu-Cu Bonding Interfaces Using Electroplated Copper and (111)-Oriented Nanotwinned Copper.

Cu-Cu joints have been adopted for ultra-high-density packaging for high-end devices. However, the atomic diffusion rate is notably low at the preferred processing temperature, resulting in clear and distinct weak bonding interfaces, which, in turn, lead to reliability issues. In this study, a new method for eliminating the bonding interfaces using two types of Cu films in Cu-Cu bonding is proposed. The difference in grain size was utilized as the primary driving force for the migration of bonding interfaces/interfacial grain boundaries. Additionally, the columnar nanotwinned Cu structure acted as a secondary driving force, making the migration more significant. When bonded at 300 °C, the grains from one side grew and extended to the bottom, eliminating the bonding interfaces. A mechanism for the evolution of the Cu bonding interfaces/interfacial grain boundaries is proposed.

The application of bronchoscopy in the assessment of immune checkpoint inhibitor-related pneumonitis severity and recurrence.

To explore the role of bronchoscopy for the assessment of checkpoint inhibitor pneumonitis (CIP), a retrospective single-center study was conducted to assess patients diagnosed with CIP at grade 2 or above and also underwent bronchoscopy between January 2020 and December 2022. Clinical data and bronchoscopic findings were recorded. The treatment data and prognosis information were collected. Twenty-one patients who underwent bronchoscopy and were diagnosed with CIP were enrolled in this study. All patients underwent bronchoalveolar lavage fluid (BALF) analysis. Of them, T lymphocyte subsets of BALF were tested in 15 cases. Transbronchial cryobiopsy (TBCB) was performed in 8 patients, and transbronchial lung biopsy was performed in 5 patients. 3 patients developed pneumothorax after TBCB and all recovered without serious compilations.14 patients experienced grade 2 CIP, while 7 patients ≥ grade 3 CIP. Symptoms were improved in 19 (90.5%) patients after standard treatment adhering to CIP guidelines. However, 5 patients relapsed during steroid tapering. Factors related to the severity and recurrence of CIP were analyzed. Patients with previous interstitial lung disease (ILD) were more likely to develop high grade CIP than those without [83.3% (5/6) versus 15.4% (3/15), P = 0.011].The odds ratio (OR) was 32.5 (95% CI 2.284-443.145, P = 0.009). Increased BALF lymphocyte percentage was associated with high grade CIP, OR 1.095 (95% CI 1.001-1.197, P = 0.047), and higher possibility of CIP relapse, OR 1.123 (95% CI, 1.005-1.225, P = 0.040). Lymphocyte subsets were tested in 15 patients. CD4/CD8 > 1 was found in 80% (4/5) of relapsed patients and 20% (2/10) of patients without relapse (P = 0.047). The OR was 16.00 (95% CI 1.093-234.24, P = 0.043). In this retrospective study, patients with previous ILD was more likely to develop high grade CIP. Higher lymphocyte percentage in BALF was associated with high grade CIP and susceptibility to relapse during treatment of CIP. A CD4/CD8 ratio greater than 1 in lymphocyte subsets of BALF was associated with higher possibility of CIP relapse. We found that TBCB is a safe procedure in CIP patients.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Immunochromatographic strip for rapid and sensitive detection of bupirimate residues in peach, orange, and carrot.

Bupirimate (BPM) is a high-efficiency and low-toxicity fungicide used to combat powdery mildew in crops. To mitigate potential health risks to consumers resulting from improper BPM usage, we prepared a monoclonal antibody against BPM based on novel hapten synthesis, which has high sensitivity and strong specificity, and then successfully designed a colloidal gold-based immunochromatographic (ICG) strip. The newly designed ICG strip was then employed for detecting BPM residues in peach, orange, and carrot. The results show that for the peach, orange, and carrot samples, the calculated detection limits of the ICG strip are 9.36, 0.79, and 0.57 ng/g, respectively, and that it is resistant to the matrix effect and meets the maximum residue limit requirements of European Commission for BPM. Therefore, this developed ICG strip is expected to enable swift detection of BPM residues on the spot.

The effectiveness of live music intervention on psychological distress among adolescent and young adult patients undergoing hematopoietic stem cell transplantation.

OBJECTIVE: To explore the effects of live music to decrease psychological distress in adolescent and young adult (AYA) patients undergoing hematopoietic stem cell transplantation (HSCT). METHOD: A quasi-experimental study was conducted. Sixty patients undergoing HSCT were divided into two groups, receiving either 4 week of live music (n = 31) or standard care (n = 29). Psychological distress, anxiety, the severity of symptom clusters and symptom interference were measured. RESULTS: When compared with the immediately and 1 month after intervention, patients in LM intervention group had significantly lower psychological distress and anxiety level than wait-list group. AYA undergoing HSCT reported significantly milder general symptom cluster and neurological symptom cluster at T3 than at baseline. CONCLUSIONS: Live music intervention showed a positive effect on relieving psychological distress and anxiety in AYA patients undergoing HSCT. However, further researches are warranted to explore the effects of live music intervention on symptom cluster.

Endoscopic Vitrectomy Combined with 3D Heads-Up Viewing System in Treating Traumatic Ocular Injury.

Purpose: To investigate effects and complications of endoscopic vitrectomy combined with 3D heads-up viewing system in treating traumatic ocular injury. Patients and Methods. This is a retrospective interventional case series in a tertiary referral center in Taiwan, and we included patients of traumatic ocular injury, and they underwent endoscopic vitrectomy combined with a 3D heads-up viewing system. Results: Fourteen eyes of traumatic globe injury from 14 patients were studied over a 30-month period. Preoperative VA ranged from no light perception (NLP) to 6/6. Postoperative visual acuity improved in 11 of the 14 eyes (79%). Until 6 months after surgery, all eyes had attached retina. The median logMAR BCVA was 2.4 at the first visit and 1.19 at the last visit (p = 0.0028). No subject suffered from retinal detachment, endophthalmitis, or other severe complications. Conclusions: Vitrectomy using endoscopy combined with 3D heads-up viewing system allowed early evaluation and intervention in traumatic ocular injuries. Most of our cases showed both anatomical and visual acuity improvements.

Pediatric WNT medulloblastoma predisposition in intraoperative blood loss: a retrospective observational cohort study.

Introduction: Molecular subgroups influence the vascular architecture within medulloblastomas, particularly the wingless (WNT) subgroup, which contributes to its propensity for primary tumor hemorrhage. Whether this mechanism affects intraoperative blood loss remains unknown. This study aimed to assess the association between WNT medulloblastoma and the predisposition for blood loss. Methods: This was a retrospective observational study using data from a neuro-oncology center comprising molecular data on patients treated between December 31, 2014, and April 30, 2023. Differences between WNT and other subgroups in the risk of primary outcome-intraoperative blood loss were assessed using multivariable-adjusted linear regression. Results: Of the 148 patients included in the analysis, 18 patients (12.2%) had WNT, 42 (28.4%) had sonic hedgehog (SHH) TP53-wildtype, 7 (4.7%) had SHH TP53-mutant, and 81 (54.7%) were non-WNT/ non-SHH. The WNT subgroup more frequently underwent primary intratumoral hemorrhage (22% vs. 3.8%; p = 0.011). The median intraoperative blood loss was 400.00 (interquartile range [IQR] 250, 500) mL for WNT and 300.00 [200, 400] mL for the other subgroups (p = 0.136), with an adjusted ß of 135.264 (95% confidence intervals [CI], 11.701-258.827; p = 0.032). Similar results were observed in both midline and noninfiltrative margin medulloblastoma. Discussion: WNT medulloblastoma is typically associated with primary intratumoral hemorrhage and intraoperative blood loss. The validity of determining the surgical approach based on predicted molecular subtypes from imaging data is questionable. However, attempting to engage in risk communication with patients in a molecular-specific way is worthwhile to validate.

Enhancement of Abnormal Grain Growth by Surface Quenching Treatment to Eliminate Cu-Cu Bonding Interfaces Using (111)-Oriented Nanotwinned Copper.

Cu-Cu joints have been adopted for ultra-high density of packaging for high-end devices. However, the processing temperature must be kept relatively low, preferably below 300 °C. In this study, a novel surface modification technique, quenching treatment, was applied to achieve Cu-to-Cu direct bonding using (111)-oriented nanotwinned Cu. The quenching treatment enabled grain growth across the Cu-Cu bonding interface at 275 °C. During quenching treatment, strain energy was induced in the Cu film, resulting in a wrinkled surface morphology. To analyze the strain energy, we utilized an electron backscattered diffraction system to obtain crystallographic information and confirmed it using kernel average misorientation analysis.

Prevalence and Neurological Outcomes of Comatose Patients With Extracorporeal Membrane Oxygenation.

OBJECTIVES: To investigate prevalence, risk factors, and in-hospital outcomes of comatose extracorporeal membrane oxygenation (ECMO) patients. DESIGN: Retrospective observational. SETTING: Tertiary academic hospital. PARTICIPANTS: Adults received venoarterial (VA) or venovenous (VV) ECMO support between November 2017 and April 022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined 24-hour off sedation as no sedative infusion (except dexmedetomidine) or paralytics administration over a continuous 24-hour period while on ECMO. Off-sedation coma (comaoff) was defined as a Glasgow Coma Scale score of ≤8 after achieving 24-hour off sedation. On-sedation coma (comaon) was defined as a Glasgow Coma Scale score of ≤8 during the entire ECMO course without off sedation for 24 hours. Neurological outcomes were assessed at discharge using the modified Rankin scale (good, 0-3; poor, 4-6). We included 230 patients (VA-ECMO 143, 65% male); 24-hour off sedation was achieved in 32.2% VA-ECMO and 26.4% VV-ECMO patients. Among all patients off sedation for 24 hours (n = 69), 56.5% VA-ECMO and 52.2% VV-ECMO patients experienced comaoff. Among those unable to be sedation free for 24 hours (n = 161), 50.5% VA-ECMO and 17.2% VV-ECMO had comaon. Comaoff was associated with poor outcomes (p < 0.05) in VA-ECMO and VV-ECMO groups, whereas comaon only impacted the VA-ECMO group outcomes. In a multivariable analysis, requirement of renal replacement therapy was an independent risk factor for comaoff after adjusting for ECMO configuration, after adjusting for ECMO configuration, acute brain injury, pre-ECMO partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, and bicarbonate level (worst value within 24 hours before cannulation). CONCLUSIONS: Comaoff was common and associated with poor outcomes at discharge. Requirement of renal replacement therapy was an independent risk factor.

Unmasking Spatial Heterogeneity in Phytotoxicology Mechanisms Induced by Carbamazepine by Mass Spectrometry Imaging and Multiomics Analyses.

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.

Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Novel diagnostic and prognostic approach for rapidly progressive dementias: Indicators based on amyloid/tau/neurodegeneration (ATN) framework.

AIMS: Apply established cerebrospinal fluid (CSF) and serum biomarkers and novel combined indicators based on the amyloid/tau/neurodegeneration (ATN) framework to improve diagnostic and prognostic power in patients with rapidly progressive dementias (RPDs). METHODS: CSF and serum biomarkers of Alzheimer's disease (AD) common neuropathology including Aß42, Aß40, p-Tau, and t-Tau were measured in cognitively normal (CN) controls (n = 33) and three RPD groups with rapidly progressive AD (rpAD, n = 23), autoimmune encephalitis (AE, n = 25), and Creutzfeldt-Jakob disease (CJD, n = 28). Logistic regression and multiple linear regression were used for producing combined indicators and prognostic assessment, respectively, including A&T, A&N, T&N, A&T&N, etc. RESULTS: Combined diagnostic indicator with A&T&N had the potential for differentiating AE from other types of RPDs, identifying 62.51% and 75% of AE subjects based on CSF and serum samples, respectively, compared to 39.13% and 37.5% when using autoantibodies. CSF t-Tau was associated with survival in the CJD group (adjusted R-Square = 0.16, p = 0.02), and its prognosis value improved when using combined predictors based on the ATN framework (adjusted R-Square = 0.273, p = 0.014). CONCLUSION: Combined indicators based on the ATN framework provide a novel perspective for establishing biomarkers for early recognition of RPDs due to treatment-responsive causes.

A Summed Score From Cardiopulmonary Exercise Test Parameters Predicts 1-Year Mortality in Newly Diagnosed Interstitial Lung Disease.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a unique diagnostic tool that assesses the functional capacity of the heart, lungs, and peripheral oxidative system in an integrated manner. However, the clinical utility of CPET for evaluating interstitial lung disease (ILD) remains uncertain. The objective of this study was to determine the predictive value of CPET for mortality in subjects with ILD. METHODS: We prospectively enrolled subjects with ILD who underwent CPET at a tertiary medical center in Taiwan and followed up their survival status for 12 months. Mortality prediction was based on comparing CPET parameters between subjects who survived and those who died. We further analyzed CPET parameters that showed significant differences using receiver operating characteristic curves to identify their optimal cutoff values. RESULTS: A total of 106 newly diagnosed subjects with ILD underwent CPET, and the 1-y mortality rate was 7.5%. Six CPET variables were found to be significant predictors of mortality: peak oxygen consumption, oxygen pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1 min after CPET, minute ventilation to carbon dioxide output slope, and functional aerobic impairment. We calculated a summed score by adding the number of CPET variables that exceeded their cutoff values. Subjects with a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects with scores of 0-5 had a survival rate of 98%. CONCLUSIONS: In conclusion, the summed score represents a useful tool for screening patients with ILD who can undergo a CPET to determine their prognosis.

Ex vivo biomechanical investigations of combined extra- and intracapsular stabilization in canines with cranial cruciate ligament deficiency.

Intracapsular reconstruction (ICR) has long been recommended as a treatment for cranial cruciate ligament deficiency (CCLD) in dogs, but it has fallen out of favor due to its inferior long-term functional outcomes. These outcomes may be attributed to the poor stiffness and strength of the graft in the early period before ligamentization is completed. Additional placement of extracapsular sutures to mechanically protect the graft during the ligamentization process may be a viable method to address this problem. However, the biomechanical effect of this combined surgical approach remains unknown. This study aimed to evaluate the 3D kinematics of the CCLD stifle in dogs in response to ICR and combined extra- and intracapsular reconstruction (CEICR). Twelve hindlimbs were collected from nine cadavers of mature dogs. The limbs were tested using a custom-made testing apparatus that reproduces their sagittal plane kinematics during the stance phase. Four statuses of stifle joints were tested, namely, (a) cranial cruciate ligament (CCL) intact; (b) CCLD; (c) CCLD stifle stabilized by CEICR; and (d) CCLD stifle stabilized by ICR only. Three-dimensional stifle kinematics at the 5 instances of the stance phase were measured with an optoelectronic system. The results showed that ICR marginally corrects the increased adduction, internal rotation, and caudodistal stifle joint center displacement that occur as a result of CCLD. CEICR led to better restoration of the stifle kinematics, especially with respect to the internal rotation and cranial translation stabilities. Furthermore, CEICR only resulted in minor excessive restraints on other motion components. The findings indicated that the additional lateral fabellotibial suture offers immediate stability to the stifle, consequently lowering the risk of graft over-elongation in the short term postoperatively. Considering the propensity for the extracapsular suture to degrade over time, further in vivo studies are warranted to explore the long-term effects of the CEICR procedure.

Topical JAK inhibition ameliorates EGFR inhibitor-induced rash in rodents and humans.

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.

Paternal care plasticity: males care more for early- than late-developing embryos in an arboreal breeding treefrog.

BACKGROUND: Parental care benefits offspring but comes with costs. To optimize the trade-off of costs and benefits, parents should adjust care based on intrinsic and/or extrinsic conditions. The harm to offspring hypothesis suggests that parents should invest more in younger offspring than older offspring because younger offspring are more vulnerable. However, this hypothesis has rarely been comprehensively tested, as many studies only reveal an inverse correlation between parental care and offspring age, without directly testing the effects of offspring age on their vulnerability. To test this hypothesis, we studied Kurixalus eiffingeri, an arboreal treefrog with paternal care. We first performed a field survey by monitoring paternal care during embryonic development. Subsequently, we conducted a field experiment to assess the prevalence of egg predators (a semi-slug, Parmarion martensi) and the plasticity of male care. Finally, we conducted a laboratory experiment to assess how embryo age affects predation by P. martensi. RESULTS: Our results showed that (1) male attendance and brooding frequency affected embryo survival, and (2) males attended and brooded eggs more frequently in the early stage than in the late stage. The experimental results showed that (3) males increased attendance frequency when the predators were present, and (4) the embryonic predation by the semi-slug during the early was significantly higher than in the late stage. CONCLUSIONS: Our findings highlight the importance of paternal care to embryo survival, and the care behavior is plastic. Moreover, our results provide evidence consistent with the predictions of the harm to offspring hypothesis, as males tend to care more for younger offspring which are more vulnerable.

The identification of hub genes associated with pure ground glass nodules using weighted gene co-expression network analysis.

BACKGROUND: Whether there are invasive components in pure ground glass nodules(pGGNs) in the lungs is still a huge challenge to forecast. The objective of our study is to investigate and identify the potential biomarker genes for pure ground glass nodule(pGGN) based on the method of bioinformatics analysis. METHODS: To investigate differentially expressed genes (DEGs), firstly the data obtained from the gene expression omnibus (GEO) database was used.Next Weighted gene co-expression network analysis (WGCNA) investigate the co-expression network of DEGs. The black key module was chosen as the key one in correlation with pGGN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were done. Then STRING was uesd to create a protein-protein interaction (PPI) network, and the chosen module genes were analyzed by Cytoscape software.In addition the polymerase chain reaction (PCR) was used to evaluate the value of these hub genes in pGGN patients' tumor tissues compared to controls. RESULTS: A total of 4475 DEGs were screened out from GSE193725, then 225 DEGs were identified in black key module, which were found to be enriched for various functions and pathways, such as extracellular exosome, vesicle, ribosome and so on. Among these DEGs, 6 overlapped hub genes with high degrees of stress method were selected. These hub genes include RPL4, RPL8, RPLP0, RPS16, RPS2 and CCT3.At last relative expression levels of CCT3 and RPL8 mRNA were both regulated in pGGN patients' tumor tissues compared to controls. CONCLUSIONS: To summarize, the determined DEGs, pathways, modules, and overlapped hub genes can throw light on the potential molecular mechanisms of pGGN.

Mac-2 binding protein glycosylation isomer at 5 years of antiviral therapy predict hepatocellular carcinoma and mortality beyond year 5 in chronic hepatitis B patients with cirrhosis.

Whether serum Mac-2 binding protein glycosylation isomer (M2BPGi) level at year 5 of treatment could predict hepatocellular carcinoma (HCC) development and mortality beyond year 5 of entecavir or tenofovir disoproxil fumarate (TDF) treatment in chronic hepatitis B (CHB) patients with cirrhosis remain unclear. This retrospective study investigated the role of M2BPGi level at year 5 of treatment in predicting HCC and mortality beyond year 5 in CHB patients with cirrhosis. This study analyzed 1385 cirrhotic patients receiving entecavir or TDF treatment. Of them, 899 patients who did not develop HCC within the first 5 years of treatment were enrolled. In the entire cohort, there was no significant difference in the annual incidence of HCC before and after year 5 of entecavir or TDF treatment (P = 0.455). Multivariable Cox analysis identified old age, higher AFP and M2BPGi levels at 5 years of treatment as independent predictors of HCC occurrence beyond year 5. We developed the HCC risk prediction model, AMA, based on age, M2BPGi and AFP levels at 5 years of treatment, with the total score ranging from 0 to 8. The AMA model accurately categorized patients into low (≤2), medium (2-5), and high (≥5) risk groups in the development and validation groups (P<0.001) and exhibited good discriminant function in predicting HCC beyond year 5 in cirrhotic patients (AUROC: 0.743 at 5 years). The M2BPGi of 1.0 COI at 5 years of treatment stratified the risk of all-cause and liver-related mortality beyond year 5 (P<0.001). In conclusions, M2BPGi level at 5 years of treatment is a useful marker for predicting HCC development and mortality beyond year 5 of entecavir or TDF therapy in CHB patients with cirrhosis.