Non-canonical phosphoglycerate dehydrogenase activity promotes liver cancer growth via mitochondrial translation and respiratory metabolism.

Phosphoglycerate dehydrogenase (PHGDH) is a key serine biosynthesis enzyme whose aberrant expression promotes various types of tumors. Recently, PHGDH has been found to have some non-canonical functions beyond serine biosynthesis, but its specific mechanisms in tumorigenesis remain unclear. Here, we show that PHGDH localizes to the inner mitochondrial membrane and promotes the translation of mitochondrial DNA (mtDNA)-encoded proteins in liver cancer cells. Mechanistically, we demonstrate that mitochondrial PHGDH directly interacts with adenine nucleotide translocase 2 (ANT2) and then recruits mitochondrial elongation factor G2 (mtEFG2) to promote mitochondrial ribosome recycling efficiency, thereby promoting mtDNA-encoded protein expression and subsequent mitochondrial respiration. Moreover, we show that treatment with a mitochondrial translation inhibitor or depletion of mtEFG2 diminishes PHGDH-mediated tumor growth. Collectively, our findings uncover a previously unappreciated function of PHGDH in tumorigenesis acting via promotion of mitochondrial translation and bioenergetics.

Recycling and metabolic flexibility dictate life in the lower oceanic crust.

The lithified lower oceanic crust is one of Earth's last biological frontiers as it is difficult to access. It is challenging for microbiota that live in marine subsurface sediments or igneous basement to obtain sufficient carbon resources and energy to support growth1-3 or to meet basal power requirements4 during periods of resource scarcity. Here we show how limited and unpredictable sources of carbon and energy dictate survival strategies used by low-biomass microbial communities that live 10-750 m below the seafloor at Atlantis Bank, Indian Ocean, where Earth's lower crust is exposed at the seafloor. Assays of enzyme activities, lipid biomarkers, marker genes and microscopy indicate heterogeneously distributed and viable biomass with ultralow cell densities (fewer than 2,000 cells per cm3). Expression of genes involved in unexpected heterotrophic processes includes those with a role in the degradation of polyaromatic hydrocarbons, use of polyhydroxyalkanoates as carbon-storage molecules and recycling of amino acids to produce compounds that can participate in redox reactions and energy production. Our study provides insights into how microorganisms in the plutonic crust are able to survive within fractures or porous substrates by coupling sources of energy to organic and inorganic carbon resources that are probably delivered through the circulation of subseafloor fluids or seawater.

RAP80 phase separation at DNA double-strand break promotes BRCA1 recruitment.

RAP80 has been characterized as a component of the BRCA1-A complex and is responsible for the recruitment of BRCA1 to DNA double-strand breaks (DSBs). However, we and others found that the recruitment of RAP80 and BRCA1 were not absolutely temporally synchronized, indicating that other mechanisms, apart from physical interaction, might be implicated. Recently, liquid-liquid phase separation (LLPS) has been characterized as a novel mechanism for the organization of key signaling molecules to drive their particular cellular functions. Here, we characterized that RAP80 LLPS at DSB was required for RAP80-mediated BRCA1 recruitment. Both cellular and in vitro experiments showed that RAP80 phase separated at DSB, which was ascribed to a highly disordered region (IDR) at its N-terminal. Meanwhile, the Lys63-linked poly-ubiquitin chains that quickly formed after DSBs occur, strongly enhanced RAP80 phase separation and were responsible for the induction of RAP80 condensation at the DSB site. Most importantly, abolishing the condensation of RAP80 significantly suppressed the formation of BRCA1 foci, encovering a pivotal role of RAP80 condensates in BRCA1 recruitment and radiosensitivity. Together, our study disclosed a new mechanism underlying RAP80-mediated BRCA1 recruitment, which provided new insight into the role of phase separation in DSB repair.

Emergence of multiple fluconazole-resistant Candida parapsilosis sensu stricto clones with persistence and transmission in China.

OBJECTIVES: We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance. METHODS: Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations. RESULTS: Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1-29 months. Clusters harbouring Erg11Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K, lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2-8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles. CONCLUSIONS: This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F, and the first demonstration of the mutations Erg11G307A, Mrr1Q625K, Tac1L263S, Tac1D440Y and Tac1T492M as conferring resistance to azoles.

Comprehensive Genomic and Transcriptomic Analysis of Sclerosing Pneumocytoma.

Sclerosing pneumocytoma is a rare and distinct lung neoplasm whose histogenesis and molecular alterations are the subject of ongoing research. Our recent study revealed that AKT1 internal tandem duplications (ITD), point mutations, and short indels were present in almost all tested sclerosing pneumocytomas, suggesting that AKT1 mutations are a major driving oncogenic event in this tumor. Although the pathogenic role of AKT1 point mutations is well established, the significance of AKT1 ITD in oncogenesis remains largely unexplored. We conducted comprehensive genomic and transcriptomic analyses of sclerosing pneumocytoma to address this knowledge gap. RNA-sequencing data from 23 tumors and whole-exome sequencing data from 44 tumors were used to obtain insights into their genetic and transcriptomic profiles. Our analysis revealed a high degree of genetic and transcriptomic similarity between tumors carrying AKT1 ITD and those with AKT1 point mutations. Mutational signature analysis revealed COSMIC signatures 1 and 5 as the prevailing signatures of sclerosing pneumocytoma, associated with the spontaneous deamination of 5-methylcytosine and an unknown etiology, respectively. RNA-sequencing data analysis revealed that the sclerosing pneumocytoma gene expression profile is characterized by activation of the PI3K/AKT/mTOR pathway, which exhibits significant similarity between tumors harboring AKT1 ITD and those with AKT1 point mutations. Notably, an upregulation of SOX9, a transcription factor known for its involvement in fetal lung development, was observed in sclerosing pneumocytoma. Specifically, SOX9 expression was prominent in the round cell component, whereas it was relatively lower in the surface cell component of the tumor. To the best of our knowledge, this is the first comprehensive investigation of the genomic and transcriptomic characteristics of sclerosing pneumocytoma. Results of the present study provide insights into the molecular attributes of sclerosing pneumocytoma and a basis for future studies of this enigmatic tumor.

Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review.

CAPZA2 encodes the α2 subunit of CAPZA, which is vital for actin polymerization and depolymerization in humans. However, understanding of diseases associated with CAPZA2 remains limited. To date, only three cases have been documented with neurodevelopmental abnormalities such as delayed motor development, speech delay, intellectual disability, hypotonia, and a history of seizures. In this study, we document a patient who exhibited seizures, mild intellectual disability, and impaired motor development yet did not demonstrate speech delay or hypotonia. The patient also suffered from recurrent instances of respiratory infections, gastrointestinal and allergic diseases. A novel de novo splicing variant c.219+1 G > A was detected in the CAPZA2 gene through whole-exome sequencing. This variant led to exon 4 skipping in mRNA splicing, confirmed by RT-PCR and Sanger sequencing. To our knowledge, this is the third study on human CAPZA2 defects, documenting the fourth unambiguously diagnosed case. Furthermore, this splicing mutation type is reported here for the first time. Our research offers additional support for the existence of a CAPZA2-related non-syndromic neurodevelopmental disorder. Our findings augment our understanding of the phenotypic range associated with CAPZA2 deficiency and enrich the knowledge of the mutational spectrum of the CAPZA2 gene.

Striatal and Extrastriatal Monoaminergic Disruption in Progressive Supranuclear Palsy.

BACKGROUND: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18F-9-fluoropropyldihydrotetrabenazine (18F-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). OBJECTIVE: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using 18F-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. METHODS: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using 18F-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. RESULTS: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. CONCLUSIONS: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. © 2024 International Parkinson and Movement Disorder Society.

Gut microbiota modulation: a narrative review on a novel strategy for prevention and alleviation of ovarian aging.

The global rise in life expectancy corresponds with a delay in childbearing age among women. Ovaries, seen as the chronometers of female physiological aging, demonstrate features of sped up aging, evidenced by the steady decline in both the quality and quantity of ovarian follicles from birth. The multifaceted pathogenesis of ovarian aging has kindled intensive research interest from the biomedical and pharmaceutical sectors. Novel studies underscore the integral roles of gut microbiota in follicular development, lipid metabolism, and hormonal regulation, forging a nexus with ovarian aging. In this review, we outline the role of gut microbiota in ovarian function (follicular development, oocyte maturation, and ovulation), compile and present gut microbiota alterations associated with age-related ovarian aging. We also discuss potential strategies for alleviating ovarian aging from the perspective of gut microbiota, such as fecal microbiota transplantation and probiotics.

Genome-wide analysis of in vivo-evolved Candida auris reveals multidrug-resistance mechanisms.

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.

Subjective experience of parent-child relationship in adolescents with congenital heart disease: A qualitative study.

PURPOSE: To explore the parent-child relationship through the subjective experience of adolescents with congenital heart disease (CHD). DESIGN AND METHODS: A descriptive phenomenology approach was adopted. Twelve adolescents aged from 12 to 18 years with CHD were recruited from the pediatric cardiology clinics at two medical centers in Taiwan. Data were collected through in-depth interviews. Data were analyzed using Colaizzi's phenomenological analysis method, and results were reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines. RESULTS: The experiences of the adolescents with CHD revealed five themes: 1. the enhancement of self-worth through parents' love; 2. the importance of parental support in desperate situations; 3. the development of a sense of security through mutual understanding; 4. growth under parental expectations; and 5. parental overcontrol disguised as love. CONCLUSIONS: The parent-child relationship encompasses both positive and negative experiences. Adolescents prioritize their relationship with parents over that with peers. PRACTICE IMPLICATIONS: Nurses caring for adolescents with CHD can improve care by recognizing the influence of parental love, support in challenges, mutual understanding, parental expectations, and potential negative consequences of overcontrol. This insight guides effective guidance for adolescents, enhancing parent-child interactions and overall well-being.

DIEP Donor Site Satisfaction between Patients with and without History of Pregnancy.

BACKGROUND: With the success of free autologous breast reconstruction, the abdominal donor site is now an important consideration, especially in patients of childbearing age. In our institution, there are increasing patients who have successfully undergone the deep inferior epigastric artery perforator (DIEP) flap despite previous pregnancy. This study aims to answer questions on the effect of the donor site on pregnancy and vice versa. METHODS: A retrospective cohort study was conducted to identify breast cancer patients who received a free DIEP flap for breast reconstruction from January 2018 to August 2020. Patients were allocated to two groups according to whether they had prior pregnancies with successful deliveries. Demographics, flap-related parameters, surgical outcomes on breast and abdomen, and patient-reported outcome (Breast-Q questionnaire) were analyzed. Patients were excluded if follow-up time was less than 1 year, or if there was incomplete medical records or Breast-Q replies. RESULTS: Ninety-nine of 116 patients had had successful pregnancies with delivery, 17 of them remained nulliparous. No statistically significant differences existed between groups regarding demographic data, flap-related parameters, surgical outcomes on breast and abdomen. Nulliparous patients exhibited significantly lower score in physical well-being in the abdomen domain compared with delivery-experienced patients (62.1 vs. 73.4, p = 0.025). Significantly, nulliparous patients felt more tightness and pulling of the abdominal wall than the delivery-experienced patients (2.9 vs. 3.7; p = 0.05 and 3.5 vs. 4.0; p = 0.04). CONCLUSION: Free DIEP flap can be transferred safely in nulliparous patients despite a slight increase in abdominal tightness and abdominal pulling. Precise flap design and surgical approaches may help to minimize the abdominal discomfort especially on young, normal body mass index, and nonchildbearing patients.

[Relationship Between Cerebrovascular Reactivity and Depression in Patients With End-Stage Renal Disease].

Objective To investigate the relationship between cerebrovascular reactivity (CVR) and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease (ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale (HAMA) and Beck depression inventory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcranial Doppler sonography,and the breath-holding index (BHI) was calculated.The BHI≥0.69 and BHI<0.69 indicate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level (P=0.010),low density lipoprotein level (P=0.006),and incidence of depression (P=0.012) than the group with normal CVR.Compared with the non-depression group,the depression group displayed prolonged disease course (P=0.039),reduced body mass index (P=0.048),elevated HAMA score (P=0.001),increased incidence of anxiety (P<0.001),decreased BHI (P=0.015),and increased incidence of abnormal CVR (P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor (OR=22.915,95%CI=2.653-197.956,P=0.004) and abnormal CVR as a risk factor (OR=0.074,95%CI=0.008-0.730,P=0.026) for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.

[Consistency evaluation of multidimensional quality attributes of Atractylodis Macrocephalae Rhizoma by fusion of multi-source information].

The quality control of Chinese medicinal decoction pieces is one of the key tasks in the traditional Chinese medicine industry. In this study, multi-source information fusion was employed to fuse the data from near-infrared spectroscopy, electronic tongues, and other tests and establish an overall quality consistency evaluation method for Atractylodis Macrocephalae Rhizoma, which provided methodological support for the overall quality evaluation of Atractylodis Macrocephalae Rhizoma. The near-infrared spectroscopy information was measured in both static and dynamic states for 23 batches of Atractylodis Macrocephalae Rhizoma samples from different sources, and the electronic tongue sensory information, moisture content, and leachate content were measured. The overall quality of Atractylodis Macrocephalae Rhizoma was evaluated by multi-source information fusion. The results showed that the near-infrared spectroscopy information of 16122103, 801000509, 801000352, 701003656, HX21L01, and 160956 was different from that of other batches of Atractylodis Macrocephalae Rhizoma powder in the static state, and 701003298, 16122103, 701003656, 701003107, 801000229, and 18090404 were the different batches in the dynamic state. The moisture content showed no significant difference between batches. The leachate content in the batch 801000509 was different from that in other batches. The electronic tongue sensory information of 150721004, 151237, 160703004, HX21M01, HX21K04, HX21K01, and 601003516 was different from that of other batches. Furthermore, data layer fusion was employed to analyze the overall quality of Atractylodis Macrocephalae Rhizoma. Four batches, 150721004, HX21M01, HX21K04, and HX21K01, showed the parameters exceeding the 95% control limits and differed from the other samples in terms of the overall quality. This study integrated the information of moisture, near-infrared spectroscopy, and other sources to evaluate the quality consistency among 23 batches of Atractylodis Macrocephalae Rhizoma samples, which provides a reference for the quality consistency evaluation of Chinese medicinal decoction pieces.

2D Exfoliation Chemistry Towards Covalent Pseudo-Layered Phosphate Framework Derived by Radical/Strain-Synergistical Process.

2D compounds exfoliated from weakly bonded bulk materials with van der Waals (vdW) interaction are easily accessible. However, the strong internal ionic/covalent bonding of most inorganic crystal frameworks greatly hinders 2D material exfoliation. Herein, we first proposed a radical/strain-synergistic strategy to exfoliate non-vdW interacting pseudo-layered phosphate framework. Specifically, hydroxyl radicals (⋅OH) distort the covalent bond irreversibly, meanwhile, H2O molecules as solvents, further accelerating interlayered ionic bond breakage but mechanical expansion. The innovative 2D laminar NASICON-type Na3V2(PO4)2O2F crystal, exfoliated by ⋅OH/H2O synergistic strategy, exhibits enhanced sodium-ion storage capacity, high-rate performance (85.7 mAh g-1 at 20 C), cyclic life (2300 cycles), and ion migration rates, compared with the bulk framework. Importantly, this chemical/physical dual driving technique realized the effective exfoliation for strongly coupled pseudo-layered frameworks, which accelerates 2D functional material development.

Constant p.L424H Mutation in GTF2I in Micronodular Thymomas With Lymphoid Stroma: Evidence Supporting Close Relationship With Type A and AB Thymomas.

Micronodular thymoma with lymphoid stroma is a rare thymic neoplasm characterized by discrete nodules of epithelial tumor cells separated by abundant lymphoid stroma. The genetic features of micronodular thymoma with lymphoid stroma remain largely unexplored. Owing to the interference of abundant intratumoral, nonneoplastic lymphoid cells, a highly sensitive approach is necessary to study genetic changes in these tumors. In this study, we used a highly sensitive next-generation sequencing assay using the molecular barcoding Ion AmpliSeq HD technology to study the most commonly mutated genes in thymomas, including GTF2I, HRAS, NRAS, KRAS, and TP53. A total of 12 cases of micronodular thymomas with lymphoid stroma were tested, and 2 cases also had areas of type A thymoma in their tumor bed. Two micronodular thymic carcinomas with lymphoid stroma, a histological mimic of micronodular thymoma, were also included for comparison. Recurrent p.L424H mutations in GTF2I were found in all the cases of micronodular thymoma with lymphoid stroma but not in the cases of micronodular thymic carcinomas. In addition, 3 cases of micronodular thymoma with lymphoid stroma also had concomitant HRAS and/or KRAS mutations. Our study showed that p.L424H mutations in GTF2I is a constant genetic feature of micronodular thymoma with lymphoid stroma. This finding strongly suggests that micronodular thymoma with lymphoid stroma is closely related to type A and AB thymomas because they all share p.L424H mutations in GTF2I.

Genomic Profiling With Large-Scale Next-Generation Sequencing Panels Distinguishes Separate Primary Lung Adenocarcinomas From Intrapulmonary Metastases.

The distinction between different separate primary lung cancers (SPLCs) and intrapulmonary metastases (IPMs) is a challenging but clinically significant issue. Histopathology-based classification is the current practice; however, it is subjective and affected by interobserver variability. Recently, next-generation sequencing (NGS) panels have been used in lung cancer diagnostics. This study aimed to investigate the value of large-scale NGS panels for distinguishing between SPLCs and IPMs. A total of 32 patients with 69 lung adenocarcinomas were included. Comprehensive histopathologic assessments of multiple pulmonary adenocarcinomas were performed independently by 3 pathologists. The consensus of histopathologic classification was determined by a majority vote. Genomic analysis was performed using an amplicon-based large-scale NGS panel, targeting single-nucleotide variants and short insertions and deletions in 409 genes. Tumor pairs were classified as SPLCs or IPMs according to a predefined molecular classification algorithm. Using NGS and our molecular classification algorithm, 97.6% of the tumor pairs can be unambiguously classified as SPLCs or IPMs. The molecular classification was predictive of postoperative clinical outcomes in terms of overall survival (P = .015) and recurrence-free interval (P = .0012). There was a moderate interobserver agreement regarding histopathologic classification (κ = 0.524 at the tumor pair level). The concordance between histopathologic and molecular classification was 100% in cases where pathologists reached a complete agreement but only 53.3% where they did not. This study showed that large-scale NGS panels are a powerful modality that can help distinguish SPLCs from IPMs in patients with multiple lung adenocarcinomas and objectively provide accurate risk stratification.

Astrocyte-Neuronal Communication and Its Role in Stroke.

Astrocytes are the most abundant glial cells in the central nervous system. These cells are an important hub for intercellular communication. They participate in various pathophysiological processes, including synaptogenesis, metabolic transformation, scar production, and blood-brain barrier repair. The mechanisms and functional consequences of astrocyte-neuron signaling are more complex than previously thought. Stroke is a disease associated with neurons in which astrocytes also play an important role. Astrocytes respond to the alterations in the brain microenvironment after stroke, providing required substances to neurons. However, they can also have harmful effects. In this review, we have summarized the function of astrocytes, their association with neurons, and two paradigms of the inflammatory response, which suggest that targeting astrocytes may be an effective strategy for treating stroke.

Common and unique alterations of functional connectivity in major depressive disorder and bipolar disorder.

OBJECTIVE: Major depressive disorder (MDD) and bipolar disorder (BD) are considered whole-brain disorders with some common clinical and neurobiological features. It is important to investigate neural mechanisms to distinguish between the two disorders. However, few studies have explored the functional dysconnectivity between the two disorders from the whole brain level. METHODS: In this study, 117 patients with MDD, 65 patients with BD, and 116 healthy controls completed resting-state functional magnetic resonance imaging (R-fMRI) scans. Both edge-based network construction and large-scale network analyses were applied. RESULTS: Results found that both the BD and MDD groups showed decreased FC in the whole brain network. The shared aberrant network across patients involves the visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and ventral attention network (VAN), which is related to the processing of external stimuli. The default mode network (DMN) and the limbic network (LN) abnormalities were only found in patients with MDD. Furthermore, results showed the highest decrease in edges of patients with MDD in between-network FC in SMN-VN, whereas in VAN-VN of patients with BD. CONCLUSIONS: Our findings indicated that both MDD and BD are extensive abnormal brain network diseases, mainly aberrant in those brain networks correlated to the processing of external stimuli, especially the attention network. Specific altered functional connectivity also was found in MDD and BD groups, respectively. These results may provide possible trait markers to distinguish the two disorders.

Nephrotoxicity of immune checkpoint inhibitor combination therapy in patients with advanced renal cell carcinoma: a meta-analysis.

PURPOSE: Few data are available regarding the nephrotoxicity of immune checkpoint inhibitor (ICI) combination therapy in advanced renal cell carcinoma (RCC). This study aimed to investigate the nephrotoxicity of ICI-based combination therapy versus standard of care sunitinib in patients with advanced RCC. METHODS: We searched Embase/PubMed/Cochrane Library for relevant randomized controlled trials (RCTs). Treatment-related nephrotoxicities including increase of creatinine and proteinuria were analyzed by Review Manager 5.4 software. RESULTS: Seven RCTs involving 5239 patients were included. The analysis showed that ICI combination therapy had similar risks of any grade (RR = 1.03, 95% CI: 0.77-1.37, P = 0.87) and grade 3-5 (RR = 1.48, 95% CI: 0.19-11.66, P = 0.71) increased creatinine compared with sunitinib monotherapy. However, ICI combination therapy was associated with significantly higher risks of any grade (RR = 2.33, 95% CI: 1.54-3.51, P < 0.0001) and grade 3-5 proteinuria (RR = 2.25, 95% CI: 1.21-4.17, P = 0.01). CONCLUSIONS: This meta-analysis suggests that ICI combination therapy shows more nephrotoxicity of proteinuria than sunitinib in advanced RCC, which deserves a high attention in the clinic.

Synergistic Enhancement of Photocatalytic H2 Evolution over NH2-MIL-125 Modified with Dual Cocatalyst.

The construction of efficient photocatalysts for water splitting to enable H2 evolution is pivotal to alleviate energy issues and environmental concerns. In this work, carbon dots (CDs) were prepared by employing "green solvent" ionic liquids as carbon sources and then combined with Pt/NH2-MIL-125, resulting in the emergence of a high-efficiency photocatalyst termed CDs-Pt/NH2-MIL-125 for the first time. This composite photocatalyst exhibited outstanding photocatalytic activity in H2 production under visible light irradiation. Notably, the H2 production rate of CDs100-Pt/NH2-MIL-125 reaches up to 951.4 µmol/g/h, which was 3.1 times that of Pt/NH2-MIL-125. The characterization results indicate that CDs and Pt uniformly dispersed on the surface of NH2-MIL-125 and fabricated a synergistic compact structure, providing a high BET surface area (985 m2 g-1) and a suitable band gap. Furthermore, the distinctive embeddable-dispersed CDs and Pt, as dual cocatalyst, can harvest light and facilitate the transfer of photogenerated electrons, thereby significantly augmenting the exploitation of visible light. The plausible mechanism of photocatalytic H2 evolution over the CDs-Pt/NH2-MIL-125 catalyst was also discussed. This work introduces a promising strategy for designing high-performance CDs-MOFs-based photocatalysts, an innovative step toward achieving efficient photocatalytic water splitting for H2 production.