DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT.

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.

Olfactory deficit: a potential functional marker across the Alzheimer's disease continuum.

Alzheimer's disease (AD) is a prevalent form of dementia that affects an estimated 32 million individuals globally. Identifying early indicators is vital for screening at-risk populations and implementing timely interventions. At present, there is an urgent need for early and sensitive biomarkers to screen individuals at risk of AD. Among all sensory biomarkers, olfaction is currently one of the most promising indicators for AD. Olfactory dysfunction signifies a decline in the ability to detect, identify, or remember odors. Within the spectrum of AD, impairment in olfactory identification precedes detectable cognitive impairments, including mild cognitive impairment (MCI) and even the stage of subjective cognitive decline (SCD), by several years. Olfactory impairment is closely linked to the clinical symptoms and neuropathological biomarkers of AD, accompanied by significant structural and functional abnormalities in the brain. Olfactory behavior examination can subjectively evaluate the abilities of olfactory identification, threshold, and discrimination. Olfactory functional magnetic resonance imaging (fMRI) can provide a relatively objective assessment of olfactory capabilities, with the potential to become a promising tool for exploring the neural mechanisms of olfactory damage in AD. Here, we provide a timely review of recent literature on the characteristics, neuropathology, and examination of olfactory dysfunction in the AD continuum. We focus on the early changes in olfactory indicators detected by behavioral and fMRI assessments and discuss the potential of these techniques in MCI and preclinical AD. Despite the challenges and limitations of existing research, olfactory dysfunction has demonstrated its value in assessing neurodegenerative diseases and may serve as an early indicator of AD in the future.

Quantitative and Qualitative Parameters of DCE-MRI Predict CDKN2A/B Homozygous Deletion in Gliomas.

RATIONALE AND OBJECTIVES: Homozygous deletion (HD) of CDKN2A/B holds important prognostic value in gliomas. This study aimed to explore the predictive potential of conventional MRI characteristics combined with dynamic contrast-enhanced MRI parameters in predicting CDKN2A/B HD status in gliomas. MATERIALS AND METHODS: Preoperative MRI data of 105 patients (69 without CDKN2A/B HD, and 36 with CDKN2A/B homozygous deletion) with gliomas were retrospectively collected. Conventional MRI features and dynamic contrast-enhanced-MRI qualitative parameter time-intensity curve type, quantitative parameters Ktrans, Kep, Ve, Vp, and iAUC were obtained. Logistic regression models for prediction of CDKN2A/B HD status were constructed in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. RESULTS: Multivariate analysis for all patients demonstrated that age (OR=1.103, p = 0.002) and Ktrans (OR=1.051, p < 0.001) independently predicted CDKN2A/B HD. In IDH-mutant subgroup, multivariate analysis results indicated that Ktrans (OR=1.098, p = 0.031) emerged as autonomous predictors of CDKN2A/B HD. In IDH-wild subgroup, age (OR=1.111, p = 0.002) and Ktrans (OR=1.032, p = 0.001) were independent predictors of CDKN2A/B HD according to the multivariate analysis. The areas under the receiver operating characteristic curve of the corresponding models were 0.90, 0.95 and 0.84, respectively. CONCLUSION: Ktrans can serve as valuable predictive parameters for identifying CDKN2A/B HD status in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalized treatment approaches for glioma patients.

Alleviation of Rheumatoid Arthritis by Inducing IDO Expression with Trichinella spiralis Recombinant Protein 43.

Rheumatoid arthritis (RA) represents the autoimmune disorder that shows aggressive arthritis as the main symptom. It is difficult to treat and can lead to joint deformation and function loss. At present, Trichinella spiralis (T. spiralis) antigen has attracted much attention because it plays a role in host immune regulatory mechanisms. Therefore, we selected T. spiralis recombinant protein 43 (Tsp43) to treat the bovine collagen type II (BCII)-induced mice RA model and explored its therapeutic mechanisms. This work first verified that Tsp43 could promote the expression of indoleamine 2, 3-dioxygenase (IDO) in dendritic cells (DCs) in vitro. Then, we randomized BALB/c mice (8 weeks old) into six groups, including control, phosphate buffer saline (PBS), BCII, BCII + heat inactivated Tsp43 (HiTsp43), BCII + Tsp43, and BCII + Tsp43 + 1-methyl-troptophan (1-MT) groups. To determine the therapeutic effect of Tsp43 on the BCII-induced mice RA model, relevant cytokines in each group and pathological changes in ankle joints were detected. To explore the mechanisms of Tsp43 on the BCII-induced mice RA model, we checked the expression of IDO in each group, CD4+T cell proliferation, and apoptosis. Collectively, Tsp43 decreased tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) expression in BCII-induced mice RA model and recovered the ankle injury to a certain extent. Tsp43 promoted high expression of IDO, caused expression of related apoptotic proteins in CD4+T cells, and caused apoptosis in CD4+T cells. In addition, Tsp43 reduced the proliferation of CD4+T cells. However, these effects can be inhibited by 1-MT (IDO inhibitor). These results suggested that Tsp43 played an important role in the treatment of arthritis by inhibiting the proliferation of CD4+T cells and inducing CD4+T cells apoptosis through the high expression of IDO. The purpose of this experiment was to provide a new idea for the treatment of RA and lay a foundation for the development of parasite-derived drugs for the treatment of RA.

ELONGATED HYPOTCOTYL5 and SPINE BASE SIZE1 together mediate light-regulated spine expansion in cucumber.

Plant trichome development is influenced by diverse developmental and environmental signals, but the molecular mechanisms involved are not well understood in most plant species. Fruit spines (trichomes) are an important trait in cucumber (Cucumis sativus L.), as they affect both fruit smoothness and commercial quality. Spine Base Size1 (CsSBS1) has been identified as essential for regulating fruit spine size in cucumber. Here, we discovered that CsSBS1 controls a season-dependent phenotype of spine base size in wild-type plants. Decreased light intensity led to reduced expression of CsSBS1 and smaller spine base size in wild-type plants, but not in the mutants with CsSBS1 deletion. Additionally, knockout of CsSBS1 resulted in smaller fruit spine base size and eliminated the light-induced expansion of spines. Overexpression of CsSBS1 increased spine base size and rescued the decrease in spine base size under low light conditions. Further analysis revealed that ELONGATED HYPOTCOTYL5 (HY5), a major transcription factor involved in light signaling pathways, directly binds to the promoter of CsSBS1 and activates its expression. Knockout of CsHY5 led to smaller fruit spine base size and abolished the light-induced expansion of spines. Taken together, our study findings have clarified a CsHY5-CsSBS1 regulatory module that mediates light-regulated spine expansion in cucumber. This finding offers a strategy for cucumber breeders to develop fruit with stable appearance quality under changing light conditions.

Achieving High-Performance Electrocatalytic Water Oxidation on Ni(OH)2 with Optimized Intermediate Binding Energy Enabled by S-Doping and CeO2 -Interfacing.

The adsorption energy of the reaction intermediates has a crucial influence on the electrocatalytic activity. Ni-based materials possess high oxygen evolution reaction (OER) performance in alkaline, however too strong binding of *OH and high energy barrier of the rate-determining step (RDS) severely limit their OER activity. Herein, a facile strategy is shown to fabricate novel vertical nanorod-like arrays hybrid structure with the interface contact of S-doped Ni(OH)2 and CeO2 in situ grown on Ni foam (S-Ni(OH)2 /CeO2 /NF) through a one-pot route. The alcohol molecules oxidation reaction experiments and theoretical calculations demonstrate that S-doping and CeO2 -interfacing significantly modulate the binding energies of OER intermediates toward optimal value and reduce the energy barrier of the RDS, contributing to remarkable OER activity for S-Ni(OH)2 /CeO2 /NF with an ultralow overpotential of 196 mV at 10 mA cm-2 and long-term durability over 150 h for the OER. This work offers an efficient doping and interfacing strategy to tune the binding energy of the OER intermediates for obtaining high-performance electrocatalysts.

Retroperitoneoscopic Clampless, Sutureless Hybrid Therapy in the Management of Renal Hilar Tumors.

OBJECTIVE: We aimed to investigate the outcomes and feasibility of a retroperitoneoscopic clampless, sutureless hybrid technique in the management of renal hilar tumors. METHODS: A retrospective cohort of consecutive patients with renal hilar tumors who received retroperitoneoscopic clampless, sutureless hybrid therapy between January 2017 and April 2021 was included. The hybrid surgical technique involved microwave ablation (MWA), followed by clampless tumor enucleation and sutureless hemostasis. Surgical, pathological, and oncological outcomes were recorded and analyzed. RESULTS: Sixty patients were included in this study. The median tumor size was 3.5 cm (2-5), the median RENAL score was 7 (range 6-10), the median operative time was 110 min (70-130), and the median estimated blood loss was 80 mL (30-130). The median length of postoperative hospital stay was 3 days (2-4), and no warm ischemia time was observed, except in one patient who required conversion to conventional on-clamp laparoscopic partial nephrectomy (LPN) with a 10 min warm ischemia time. Three minor complications (Clavien-Dindo grade I) and one major complication (Clavien-Dindo grade III) were recorded postoperatively. Thus far, no blood transfusions have been required. Renal dysfunction or tumor recurrence did not occur within a median follow-up of 45 months. CONCLUSION: The retroperitoneoscopic hybrid technique involving MWA, clampless tumor enucleation, and sutureless hemostasis is a feasible and safe option for the management of selective renal hilar tumors. Complete tumor removal with maximal renal function preservation can be achieved, with a low complication rate.

Genome Assembly of Cordia subcordata, a Coastal Protection Species in Tropical Coral Islands.

Cordia subcordata trees or shrubs, belonging to the Boraginaceae family, have strong resistance and have adapted to their habitat on a tropical coral island in China, but the lack of genome information regarding its genetic background is unclear. In this study, the genome was assembled using both short/long whole genome sequencing reads and Hi-C reads. The assembled genome was 475.3 Mb, with 468.7 Mb (99.22%) of the sequences assembled into 16 chromosomes. Repeat sequences accounted for 54.41% of the assembled genome. A total of 26,615 genes were predicted, and 25,730 genes were functionally annotated using different annotation databases. Based on its genome and the other 17 species, phylogenetic analysis using 336 single-copy genes obtained from ortholog analysis showed that C. subcordata was a sister to Coffea eugenioides, and the divergence time was estimated to be 77 MYA between the two species. Gene family evolution analysis indicated that the significantly expanded gene families were functionally related to chemical defenses against diseases. These results can provide a reference to a deeper understanding of the genetic background of C. subcordata and can be helpful in exploring its adaptation mechanism on tropical coral islands in the future.

A Minireview of the Solid-State Electrolytes for Zinc Batteries.

Aqueous zinc-ion batteries (ZIBs) have gained significant recognition as highly promising rechargeable batteries for the future due to their exceptional safety, low operating costs, and environmental advantages. Nevertheless, the widespread utilization of ZIBs for energy storage has been hindered by inherent challenges associated with aqueous electrolytes, including water decomposition reactions, evaporation, and liquid leakage. Fortunately, recent advances in solid-state electrolyte research have demonstrated great potential in resolving these challenges. Moreover, the flexibility and new chemistry of solid-state electrolytes offer further opportunities for their applications in wearable electronic devices and multifunctional settings. Nonetheless, despite the growing popularity of solid-state electrolyte-based-ZIBs in recent years, the development of solid-state electrolytes is still in its early stages. Bridging the substantial gap that exists is crucial before solid-state ZIBs become a practical reality. This review presents the advancements in various types of solid-state electrolytes for ZIBs, including film separators, inorganic additives, and organic polymers. Furthermore, it discusses the performance and impact of solid-state electrolytes. Finally, it outlines future directions for the development of solid-state ZIBs.

PdMo Bimetallene Coupled with MXene Nanosheets as Efficient Bifunctional Electrocatalysts for Formic Acid and Methanol Oxidation Reactions.

In this study, we demonstrate a facile soft chemistry strategy for the in situ growth of two-dimensional (2D) ultrathin PdMo bimetallene tightly coupled with Ti3C2Tx MXene nanosheets (PdMo/Ti3C2Tx) using a robust stereoassembly process. The 2D PdMo bimetallene offers numerous unsaturated Pd atoms and simultaneously induces combined bimetallic alloy and strain effects, while the Ti3C2Tx matrix effectively optimizes the electronic structure of PdMo bimetallene via a face-to-face interface interaction and guarantees exceptional electrical conductivity. As a consequence, the newly designed PdMo/Ti3C2Tx nanoarchitecture expresses remarkable electrocatalytic properties for the formic acid and methanol electro-oxidation, in terms of large electrochemically active surface areas, ultrahigh catalytic activity, strong antipoisoning ability, and dependable long-term stability, all of which are better than those of conventional Pd nanoparticle catalysts supported by Ti3C2Tx and carbon matrices.

Effect of Additional Mass on Natural Frequencies of Weight-Sensing Structures.

The phenomena of variability and interference in the natural frequencies of weight-sensing structures applied in complex working conditions must solve the problem of reducing or eliminating resonance under low-frequency vibrations to maximize stability, accuracy and reliability. The influence laws of the additional mass with relevant characteristics on the natural frequencies, which include the components of mass, stiffness and center-of-mass distribution, etc. Firstly, the theoretical formulas of the mathematical model are given based on different characteristics of the weight-sensing structure, and various combinations of additional masses on the weight-sensing structures are adjusted in the X-, Y-, and Z-directions. The key factors to be specifically considered in the theoretical formulas are discussed through simulation analysis and experimental validation. Secondly, the locking strength of the fastening screws of some components was changed, and another component was placed on the experimental platform in the experiment. The results show that the mass, center-of-mass, stiffness distribution and other factors of the additional mass have different effects on the natural frequencies, which are important for the demand for high-precision, high-stability weighing measurement. The results of this research can provide an effective scientific evaluation basis for the reliable prediction of natural frequencies.

Construction and application of a new watermelon germplasm with the phenotype of dwarf and branchless.

Watermelon (Citrullus lanatus) is a widely cultivated cucurbitaceae crop appreciated by consumers worldwide. However, the long vine and abundant lateral branches of currently cultivated watermelon varieties hinder light simplification and mechanized cultivation, affecting plant spacing and row spacing requirements. To address this, the development of watermelon with dwarf and branchless traits has become a crucial direction for the industry. In previous studies, the genes controlling dwarf (Cldw-1) and branchless (Clbl) traits were mapped and cloned. Marker-assisted selection markers, dCAPS3 and dCAPS10, were developed for these traits, respectively. In this study, the dwarf germplasm WM102 and the branchless germplasm WCZ were crossed to obtain F1 .Further self-crossing of the F1 individuals resulted in the F2 population. Through multiple generations of self-pollination, a new watermelon germplasm DM with double mutation (dwarf and branchless) was obtained. DM exhibited stable inheritance without segregation. Moreover, DM was used as a donor parent for crossing with commercial watermelon materials, and near-isogenic lines (NILs) with the dwarf and branchless traits were developed. These NILs carry additional desirable agronomic traits and provide valuable genetic resources for future watermelon breeding programs, particularly in improving plant architecture and overall quality. The development and application of DM and NILs hold great potential for advancing the watermelon industry toward industrialization, large-scale cultivation, and enhanced plant architecture.

Natural allelic variation in the EamA-like transporter, CmSN, is associated with fruit skin netting in melon.

KEY MESSAGE: A SNP mutation in CmSN, encoding an EamA-like transporter, is responsible for fruit skin netting in melon. In maturing melon (Cucumis melo L.), the rind becomes reticulated or netted, a unique characteristic that dramatically changes the appearance of the fruit. However, little is known about the molecular basis of fruit skin netting formation in this important cucurbit crop. Here, we conducted map-based cloning of a skin netting (CmSN) locus using segregating populations derived from the cross between the smooth-fruit line H906 and the netted-fruit line H581. The results showed that CmSN was controlled by a single dominant gene and was primarily positioned on melon chromosome 2, within a physical interval of ~ 351 kb. Further fine mapping in a large F2 population narrowed this region to a 71-kb region harboring 5 genes. MELO3C010288, which encodes a protein in the EamA-like transporter family, is the best possible candidate gene for the netted phenotype. Two nonsynonymous single nucleotide polymorphisms (SNPs) were identified in the third and sixth exons of the CmSN gene and co-segregated with the skin netting (SN) phenotype among the genetic population. A genome-wide association study (GWAS) determined that CmSN is probably a domestication gene under selective pressure during the subspecies C. melo subsp. melo differentiation. The SNP in the third exon of CmSN (the leading SNP in GWAS) revealed a bi-allelic diversity in natural accessions with SN traits. Our results lay a foundation for deciphering the molecular mechanism underlying the formation of fruit skin netting in melon, as well as provide a strategy for genetic improvement of netted fruit using a marker-assisted selection approach.

Epigenome-wide development and validation of a prognostic methylation score in intrahepatic cholangiocarcinoma based on machine learning strategies.

Background: Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma (ICC) patients. In this study, we developed a methylation signature that precisely predicts overall survival (OS) after surgery. Methods: An epigenome-wide study of DNA methylation based on whole-genome bisulfite sequencing (WGBS) was conducted for two independent cohorts (discovery cohort, n=164; validation cohort, n=170) from three hepatobiliary centers in China. By referring to differentially methylated regions (DMRs), we proposed the concept of prognostically methylated regions (PMRs), which were composed of consecutive prognostically methylated CpGs (PMCs). Using machine learning strategies (Random Forest and the least absolute shrinkage and selector regression), a prognostic methylation score (PMS) was constructed based on 14 PMRs in the discovery cohort and confirmed in the validation cohort. Results: The C-indices of the PMS for predicting OS in the discovery and validation cohorts were 0.79 and 0.74, respectively. In the whole cohort, the PMS was an independent predictor of OS [hazard ratio (HR) =8.12; 95% confidence interval (CI): 5.48-12.04; P<0.001], and the C-index (0.78) of the PMS was significantly higher than that of the Johns Hopkins University School of Medicine (JHUSM) nomogram (0.69, P<0.001), the Eastern Hepatobiliary Surgery Hospital (EHBSH) nomogram (0.67, P<0.001), American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system (0.61, P<0.001), and MEGNA prognostic score (0.60, P<0.001). The patients in quartile 4 of PMS could benefit from adjuvant therapy (AT) (HR =0.54; 95% CI: 0.32-0.91; log-rank P=0.043), whereas those in the quartiles 1-3 could not. However, other nomograms and staging system failed to do so. Further analyses of potential mechanisms showed that the PMS was associated with tumor biological behaviors, pathway activation, and immune microenvironment. Conclusions: The PMS could improve the prognostic accuracy and identify patients who would benefit from AT for ICC patients, and might facilitate decisions in treatment of ICC patients.

Lattice tensile strain cobalt phosphate with modulated hydroxide adsorption and structure transformation towards improved oxygen evolution reaction.

The adsorption energy of oxygen-containing intermediates for the oxygen evolution reaction (OER) electrocatalysts plays a key role on their electrocatalytic performances. Rational optimization and regulation of the binding energy of intermediates can effectively improve the catalytic activities. Herein, the binding strength of Co phosphate to *OH was weakened by generating lattice tensile strain via Mn replacement, which modulated the electronic structure and optimized the reactive intermediates adsorption with active sites. The tensile-strained lattice structure and stretched interatomic distance were confirmed by X-ray diffraction and extended X-ray absorption fine structure (EXAFS) spectra measurements. The as-obtained Mn-doped Co phosphate exhibits excellent OER activity with an overpotential of 335 mV at 10 mA cm-2, which is much higher than pristine Co phosphate. In-situ Raman spectra and methanol oxidation reaction experiments demonstrated that Mn-doped Co phosphate with lattice tensile strain shows optimized *OH adsorption strength, and is favorable to structure reconstruction and form highly active Co oxyhydroxide intermediate during OER process. Our work provides insight into the effects of the lattice strain on the OER activity from the standpoint of intermediate adsorption and structure transformation.

Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer.

Dormant cancer cells account for cancer recurrence, distant metastasis and drug resistance which lead to poor prognosis in colorectal cancer (CRC). However, little is known about the molecular mechanisms regulating tumor cell dormancy and how to eliminate dormant cancer cells. Recent studies indicate autophagy affects dormant tumor cell survival. Here, we found that polo-like kinases 4 (PLK4), a central regulator of the cell cycle and proliferation, plays a crucial role in regulating CRC cells dormancy both in vitro and in vivo. Downregulation of PLK4 induced dormancy and inhibited migration and invasion in different CRC cell lines. Clinically, PLK4 expression was correlated with the dormancy markers (Ki67, p-ERK, p-p38) and late recurrence in CRC tissues. Mechanistically, downregulation of PLK4 induced autophagy contributed to restoring phenotypically aggressive tumor cells to a dormant state through the MAPK signaling pathway, and inhibition of autophagy would trigger apoptosis of dormant cells. Our findings reveal that downregulation of PLK4-induced autophagy contributes to tumor dormancy and autophagy inhibition leads to apoptosis of CRC dormant cells. Our study is the first to report that downregulation PLK4 induced autophagy is an early event in CRC dormancy and highlights autophagy inhibitor as a potential therapeutic target for dormant cell elimination.

Hepatic arterial infusion chemotherapy combined with anti-PD-1/PD-L1 immunotherapy and molecularly targeted agents for advanced hepatocellular carcinoma: a real world study.

Background: Molecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC). Methods: A total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders. Results: The median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3-4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan-Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients. Conclusion: Patients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.

Synergistic structural and functional alterations in the medial prefrontal cortex of patients with high-grade gliomas infiltrating the thalamus and the basal ganglia.

Background: High-grade gliomas (HGGs) are characterized by a high degree of tissue invasion and uncontrolled cell proliferation, inevitably damaging the thalamus and the basal ganglia. The thalamus exhibits a high level of structural and functional connectivity with the default mode network (DMN). The present study investigated the structural and functional compensation within the DMN in HGGs invading the thalamus along with the basal ganglia (HITBG). Methods: A total of 32 and 22 healthy controls were enrolled, and their demographics and neurocognition (digit span test, DST) were assessed. Of the 32 patients, 18 patients were involved only on the left side, while 15 of them were involved on the right side. This study assessed the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), gray matter (GM) volume, and functional connectivity (FC) within the DMN and compared these measures between patients with left and right HITBG and healthy controls (HCs). Result: The medial prefrontal cortex (mPFC) region existed in synchrony with the significant increase in ALFF and GM volume in patients with left and right HITBG compared with HCs. In addition, patients with left HITBG exhibited elevated ReHo and GM precuneus volumes, which did not overlap with the findings in patients with right HITBG. The patients with left and right HITBG showed decreased GM volume in the contralateral hippocampus without any functional variation. However, no significant difference in FC values was observed in the regions within the DMN. Additionally, the DST scores were significantly lower in patients with HITBG, but there was no significant correlation with functional or GM volume measurements. Conclusion: The observed pattern of synchrony between structure and function was present in the neuroplasticity of the mPFC and the precuneus. However, patients with HITBG may have a limited capacity to affect the connectivity within the regions of the DMN. Furthermore, the contralateral hippocampus in patients with HITBG exhibited atrophy. Thus, preventing damage to these regions may potentially delay the progression of neurological function impairment in patients with HGG.

Structural plasticity of the contralesional hippocampus and its subfields in patients with glioma.

OBJECTIVES: To characterize the structural plasticity of the contralesional hippocampus and its subfields in patients with unilateral glioma. METHODS: 3D T1-weighted MRI images were collected from 55 patients with tumors infiltrating the left (HipL, n = 27) or right (HipR, n = 28) hippocampus, along with 30 age- and sex-matched healthy controls (HC). Gray matter volume differences of the contralesional hippocampal regions and three control regions (superior frontal gyrus, caudate nucleus, and superior occipital gyrus) were evaluated using voxel-based morphometry (VBM) analyses. Volumetric differences in the hippocampus and its subregional volume were measured using the FreeSurfer software. RESULTS: Compared with HC, patients with unilateral hippocampal glioma exhibited significantly larger gray matter volume in the contralesional hippocampus and parahippocampal regions (cluster = 571 voxels for HipL; cluster 1 = 538 voxels and cluster 2 = 88 voxels for HipR; family-wise error corrected p < 0.05). No significant alterations were found in control regions. Volumetric analyses showed the same trend in the contralesional hippocampal subregions for both patient groups, including the CA1 head, CA3 head, hippocampus amygdala transition area (HATA), fimbria, and the granule cell molecular layer of the dentate gyrus head (GC-ML-DG head). Notably, the differences of the contralesional HATA (HipL: η2 = 0.418, corrected p = 0.002; HipR: η2 = 0.313, corrected p = 0.052) and fimbria (HipL: η2 = 0.450, corrected p < 0.001; HipR: η2 = 0.358, corrected p = 0.012) still held after the Bonferroni correction. CONCLUSIONS: Our findings provide evidence for macrostructural plasticity of the contralateral hippocampus in patients with unilateral hippocampal glioma. Specifically, HATA and fimbria exhibit great potential in this process. KEY POINTS: • Glioma infiltration of the hippocampal regions induces a significant increase in gray matter volume on the contralateral side. • Specifically, the HATA and fimbria regions exhibit favorable plastic potential in the process of lesion-induced structural remolding.

Facilitating interface charge transfer via constructing NiO/NiCo2O4 heterostructure for oxygen evolution reaction under alkaline conditions.

Designing high-activity electrocatalysts to enhance the slow multielectron-transfer process of the oxygen evolution reaction (OER) is of great importance for hydrogen generation. Here, we employ hydrothermal and subsequent heat-treatment strategies to acquire nanoarrays-structured NiO/NiCo2O4 heterojunction anchored Ni foam (NiO/NiCo2O4/NF) as efficient materials for catalyzing the OER in an alkaline electrolyte. Density functional theory (DFT) results demonstrate that NiO/NiCo2O4/NF exhibits a smaller overpotential than those of single NiO/NF and NiCo2O4/NF owing to interface-triggered numerous interface charge transfer. Moreover, the superior metallic characteristics of NiO/NiCo2O4/NF further enhance its electrochemical activity toward OER. Specifically, NiO/NiCo2O4/NF delivered a current density of 50 mA cm-2 at an overpotential of 336 mV with a Tafel slope of 93.2 mV dec-1 for the OER, which are comparable with those of commercial RuO2 (310 mV and 68.8 mV dec-1). Further, an overall water splitting system is preliminarily constructed via using a Pt net as cathode and NiO/NiCo2O4/NF as anode. The water electrolysis cell performs an operating voltage of 1.670 V at 20 mA cm-2, which outperform the Pt net||IrO2 couple assembled two-electrode electrolyzer (1.725 V at 20 mA cm-2). This study proposes an efficient route to acquire multicomponent catalysts with rich interfaces for water electrolysis.