Convective Water Vapour Energy Ablation (Rezum®) versus Prostatic Urethral Lift (Urolift®); A 2-Year Prospective Study.

Introduction To compare the clinical outcomes and complication rates of Convective Water Vapour Energy Ablation (Rezum®) and Prostatic Urethral Lift (Urolift®). To identify predictive factors for treatment failures in both treatments. Materials & Methods Prospective clinico-epidemiological data of patients who underwent Urolift® or Rezum® in a single institution for Benign Prostatic Hyperplasia (BPH) was collected. The choice of intervention depended on the preference of the patients after patient-centric discussions. Results From October 2019 to October 2022, 86 patients underwent Rezum® and 62 patients underwent Urolift®. Rezum® involved a longer indwelling catheter duration (12.38±5.548 versus 1.39±3.010 days, p<0.001) compared to Urolift®. Rezum® was associated with more complications compared to Urolift® (36 (41.9%) versus 10 (16.1%) cases, p<0.001). Rezum® had more cases of hematuria (17 (19.8%) versus 4 (6.5%) cases (p=0.022)) and urinary tract infections (27 (31.4%) versus 3 (4.8%) cases, p<0.001)), compared to Urolift®. There were no significant differences in Clavien-Dindo Grade 3-5 complications between the interventions. Urolift® was associated with higher re-operation rates (5 (8.1%) versus 0 (0%) cases, p=0.010) compared Rezum®. Rezum® had higher anti-cholinergic usage rates compared to Urolift® post-operation (22 (25.6%) versus 8 (12.9%) cases, p=0.024). Both interventions showed improvement in International Prostate Symptom Score (IPSS), Quality of Life score, and peak velocity flow over the 2 years with no significant difference between the two. Based on receiver operating characteristic curve, pre-operation IPSS ≥ 16 had 95.7% sensitivity and 38.4% specificity to predict the probability of treatment failures after the interventions. Conclusions There was no difference in clinical outcomes of patients who underwent Rezum® and Urolift®. However, patients who had undergone Rezum® faced more minor complications and more required anti-cholinergic medications. Lastly, physicians should note that patients with IPSS≥16 would unlikely benefit from either intervention.

Moment neural network and an efficient numerical method for modeling irregular spiking activity.

Continuous rate-based neural networks have been widely applied to modeling the dynamics of cortical circuits. However, cortical neurons in the brain exhibit irregular spiking activity with complex correlation structures that cannot be captured by mean firing rate alone. To close this gap, we consider a framework for modeling irregular spiking activity, called the moment neural network, which naturally generalizes rate models to second-order moments and can accurately capture the firing statistics of spiking neural networks. We propose an efficient numerical method that allows for rapid evaluation of moment mappings for neuronal activations without solving the underlying Fokker-Planck equation. This allows simulation of coupled interactions of mean firing rate and firing variability of large-scale neural circuits while retaining the advantage of analytical tractability of continuous rate models. We demonstrate how the moment neural network can explain a range of phenomena including diverse Fano factor in networks with quenched disorder and the emergence of irregular oscillatory dynamics in excitation-inhibition networks with delay.

Learning to integrate parts for whole through correlated neural variability.

Neural activity in the cortex exhibits a wide range of firing variability and rich correlation structures. Studies on neural coding indicate that correlated neural variability can influence the quality of neural codes, either beneficially or adversely. However, the mechanisms by which correlated neural variability is transformed and processed across neural populations to achieve meaningful computation remain largely unclear. Here we propose a theory of covariance computation with spiking neurons which offers a unifying perspective on neural representation and computation with correlated noise. We employ a recently proposed computational framework known as the moment neural network to resolve the nonlinear coupling of correlated neural variability with a task-driven approach to constructing neural network models for performing covariance-based perceptual tasks. In particular, we demonstrate how perceptual information initially encoded entirely within the covariance of upstream neurons' spiking activity can be passed, in a near-lossless manner, to the mean firing rate of downstream neurons, which in turn can be used to inform inference. The proposed theory of covariance computation addresses an important question of how the brain extracts perceptual information from noisy sensory stimuli to generate a stable perceptual whole and indicates a more direct role that correlated variability plays in cortical information processing.

Lung image segmentation via generative adversarial networks.

Introduction: Lung image segmentation plays an important role in computer-aid pulmonary disease diagnosis and treatment. Methods: This paper explores the lung CT image segmentation method by generative adversarial networks. We employ a variety of generative adversarial networks and used their capability of image translation to perform image segmentation. The generative adversarial network is employed to translate the original lung image into the segmented image. Results: The generative adversarial networks-based segmentation method is tested on real lung image data set. Experimental results show that the proposed method outperforms the state-of-the-art method. Discussion: The generative adversarial networks-based method is effective for lung image segmentation.

[One-stage posterior debridement and spinal internal fixation for the treatment of lumbar Brucellar spondylitis].

OBJECTIVE: To explore the clinical efficacy and safety of one-stage posterior lesion removal and internal spinal fixation in patients with lumbar Brucellosis spondylitis. METHODS: The clinical data of 24 patients admitted from October 2017 to October 2022 were retrospectively analyzed, 2 patients were lost to follow-up at 10 months after surgery, at the final 22 cases were included in the study, including 13 males and 9 females with an average age of (52.00±6.89) years old, were treated with one-stage posterior lesion removal and internal spinal fixation. The operation time, intraoperative bleeding, follow-up time, erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) before and after operation were recorded. The pain visual analogue scale(VAS), Oswestry disability index(ODI), the Japanese Orthopaedic Association(JOA) score for neurofunction, American Spinal Injury Association(ASIA) spinal cord injury grade and modified MacNab criteria were ussed to evaluate the efficacy. RESULTS: All patients were followed up from 12 to 30 months with an average of (17.41±4.45) months. The operation time was 70 to 155 min with an average of (116.59±24.32) min;the intraoperative bleeding volume was 120 to 520 ml with an average of (275.00±97.53) ml. CRP and ESR levels decreased more significantly at 1 week and at the final follow-up than preoperative levels(P<0.05). VAS, JOA score and ODI at 1 week and at the latest follow-up were more significantly improved than preoperative results(P<0.05). There was no significant difference between ASIA preoperative and 1 week after operation(P>0.05), and a significant difference between preoperative and last follow-up(P<0.05). In the final follow-up, 21 patients had excellent efficacy, 1 patient had fair, and there was no recurrence during the follow-up. CONCLUSION: One-stage transpedicular lesion removal and internal spinal fixation, with few incisions and short operation time, helps the recovery of neurological function, and the prognosis meets the clinical requirements, which can effectively control Brucella spondylitis.

Modulation of optical properties and defects of ZnO films with preferred orientations by annealing in different atmospheres.

Nonpolar (100), polar (002), semipolar (101), and nonpolar (110) preferred oriented ZnO films were synthesized by regulated growth using the chemical bath deposition method. The crystallinity, surface morphology, and optical properties of ZnO films with different preferred orientations after annealing in different atmospheres were systematically investigated. The experimental results show an increase in crystallinity and a decrease in surface roughness of the films after annealing; in particular, the optical transmittance of semipolar (101) preferred oriented ZnO films was significantly higher than that of the other samples. XPS and PL spectra confirmed that annealing in argon effectively increased donor defects, whereas annealing in oxygen and ozone reduced donor defects in the films, and that ozone annealing was best suited to enhance acceptor defects in nonpolar (110) preferred oriented ZnO films. Argon annealing is the best for the enhancement of donor defects in polar (002) preferred oriented ZnO films. This work achieves modulation of optical properties and defects of ZnO films by annealing in different atmospheres, which provides new ideas for the application of ZnO materials.

Magnetocaloric effect of topological excitations in Kitaev magnets.

Traditional magnetic sub-Kelvin cooling relies on the nearly free local moments in hydrate paramagnetic salts, whose utility is hampered by the dilute magnetic ions and low thermal conductivity. Here we propose to use instead fractional excitations inherent to quantum spin liquids (QSLs) as an alternative, which are sensitive to external fields and can induce a very distinctive magnetocaloric effect. With state-of-the-art tensor-network approach, we compute low-temperature properties of Kitaev honeycomb model. For the ferromagnetic case, strong demagnetization cooling effect is observed due to the nearly free Z2 vortices via spin fractionalization, described by a paramagnetic equation of state with a renormalized Curie constant. For the antiferromagnetic Kitaev case, we uncover an intermediate-field gapless QSL phase with very large spin entropy, possibly due to the emergence of spinon Fermi surface and gauge field. Potential realization of topological excitation magnetocalorics in Kitaev materials is also discussed, which may offer a promising pathway to circumvent existing limitations in the paramagnetic hydrates.

In Situ Formed Gel Polymer Electrolytes Enable Stable Solid Electrolyte Interface for High-Performance Lithium Metal Batteries.

Carbonate-based electrolytes show distinct advantages in high-voltage cathodes but generate nonuniform and mechanically fragile solid-electrolyte interphase (SEI) in lithium (Li) metal batteries. Herein, we propose a LiF-rich SEI incorporating an in situ polymerized poly(hexamethylene diisocyanate)-based gel polymer electrolyte (GPE) to improve the homogeneity and mechanical stability of SEI. Fluoroethylene carbonate (FEC) as a fluorine-based additive for building LiF-rich SEI on Li metal electrodes. With this strategy, the assembled Li symmetric batteries cycled stably for 700 h, and the formation of byproducts on the Li electrode surface was significantly inhibited. The Li/LiFePO4 battery delivered significant capacity retention (91% retention after 800 cycles) at 1 C. With high-voltage LiNi0.8Co0.1Mn0.1O2 (NCM811) as cathode, the Li/GPE-FEC/NCM811 cell delivered a discharge capacity of 168.9 mAh g-1 with a capacity retention of 82% after 300 cycles at 0.5 C. From the above, the work could assist the rapid development of high-energy-density rechargeable Li metal batteries toward remarkable performance.

Novel machine-learning prediction tools for overall survival of patients with chondrosarcoma: Based on recursive partitioning analysis.

BACKGROUND: Chondrosarcoma (CHS), a bone malignancy, poses a significant challenge due to its heterogeneous nature and resistance to conventional treatments. There is a clear need for advanced prognostic instruments that can integrate multiple prognostic factors to deliver personalized survival predictions for individual patients. This study aimed to develop a novel prediction tool based on recursive partitioning analysis (RPA) to improve the estimation of overall survival for patients with CHS. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed, including demographic, clinical, and treatment details of patients diagnosed between 2000 and 2018. Using C5.0 algorithm, decision trees were created to predict survival probabilities at 12, 24, 60, and 120 months. The performance of the models was assessed through confusion scatter plot, accuracy rate, receiver operator characteristic (ROC) curve, and area under ROC curve (AUC). RESULTS: The study identified tumor histology, surgery, age, visceral (brain/liver/lung) metastasis, chemotherapy, tumor grade, and sex as critical predictors. Decision trees revealed distinct patterns for survival prediction at each time point. The models showed high accuracy (82.40%-89.09% in training group, and 82.16%-88.74% in test group) and discriminatory power (AUC: 0.806-0.894 in training group, and 0.808-0.882 in test group) in both training and testing datasets. An interactive web-based shiny APP (URL: https://yangxg1209.shinyapps.io/chondrosarcoma_survival_prediction/) was developed, simplifying the survival prediction process for clinicians. CONCLUSIONS: This study successfully employed RPA to develop a user-friendly tool for personalized survival predictions in CHS. The decision tree models demonstrated robust predictive capabilities, with the interactive application facilitating clinical decision-making. Future prospective studies are recommended to validate these findings and further refine the predictive model.

Regulating Astrocytes via Short Fibers for Spinal Cord Repair.

Reactive astrogliosis is the main cause of secondary injury to the central nerves. Biomaterials can effectively suppress astrocyte activation, but the mechanism remains unclear. Herein, Differentially Expressed Genes (DEGs) are identified through whole transcriptome sequencing in a mouse model of spinal cord injury, revealing the VIM gene as a pivotal regulator in the reactive astrocytes. Moreover, DEGs are predominantly concentrated in the extracellular matrix (ECM). Based on these, 3D injectable electrospun short fibers are constructed to inhibit reactive astrogliosis. Histological staining and functional analysis indicated that fibers with unique 3D network spatial structures can effectively constrain the reactive astrocytes. RNA sequencing and single-cell sequencing results reveal that short fibers downregulate the expression of the VIM gene in astrocytes by modulating the "ECM receptor interaction" pathway, inhibiting the transcription of downstream Vimentin protein, and thereby effectively suppressing reactive astrogliosis. Additionally, fibers block the binding of Vimentin protein with inflammation-related proteins, downregulate the NF-κB signaling pathway, inhibit neuron apoptosis, and consequently promote the recovery of spinal cord neural function. Through mechanism elucidation-material design-feedback regulation, this study provides a detailed analysis of the mechanism chain by which short fibers constrain the abnormal spatial expansion of astrocytes and promote spinal cord neural function.

Precut Over a Pancreatic Duct Stent Versus Transpancreatic Precut Sphincterotomy for Difficult Biliary Cannulation in Endoscopic Retrograde Cholangiopancreatography: A Retrospective Cohort Study.

BACKGROUND: Precut over a pancreatic duct stent (PPDS) and transpancreatic precut sphincterotomy (TPS) with immediate pancreatic duct stent placement are techniques employed to promote biliary access during endoscopic retrograde cholangiopancreatography (ERCP) in cases of challenging biliary cannulation. However, limited data are available to compare the efficacy of these two pancreatic stent-assisted precut sphincterotomy techniques. AIMS: The aim of this study was to compare the efficacy of PPDS versus TPS. METHODS: A retrospective analysis was performed on the clinical data of consecutive patients who underwent ERCP between April 1, 2019 and May 31, 2023. According to the selected cannulation approaches, patients were assigned to two groups. In the PPDS group, a pancreatic duct stent was initially placed, followed by needle-knife precut over the stent. In the TPS group, transpancreatic precut sphincterotomy was initially performed, followed by immediate pancreatic stent placement. The success rate of biliary cannulation and the incidence of post-ERCP pancreatitis (PEP) between the two groups were analysed. RESULTS: Among 864 patients who underwent ERCP, 46 patients were equally enrolled in the two groups. Selective bile duct cannulation was successfully achieved in 42 out of 46 (91.3%) cases using the PPDS and in 32 out of 46 (69.6%) cases using TPS technique alone, indicating significantly higher success rate of bile duct cannulation with PPDS compared to TPS (91.3% vs. 69.6%, P = 0.009). The overall success rates for bile duct cannulation were 93.5% and 97.8% in the PPDS and TPS groups, respectively, with no significant difference identified (P = 0.307). PEP occurred in 0 and 4 (8.7%) cases in the PPDS and TPS groups, respectively, with no significant difference between the two groups (8.7% vs. 0%, P = 0.117). There were no cases of bleeding or perforation in either group. CONCLUSIONS: Both PPDS and TPS followed by immediate pancreatic duct stent placement are viable options. TPS stands out for its simplicity and cost-effectiveness, while PPDS is more appropriate for patients who are at a high-risk of developing PEP.

A computational account of conflict processing during mental imagery.

Previous studies examining conflict processing within the context of a color-word Stroop task have focused on both stimulus and response conflicts. However, it has been unclear whether conflict can emerge independently of stimulus conflict. In this study, a novel arrow-gaze mental-rotation Stroop task was introduced to explore the interplay between conflict processing and mental rotation. A modelling approach was utilized to provide a process-level account of the findings. The results of our Stroop task indicate that conflict can emerge from mental rotation in the absence of stimulus conflict. The strength of this imagery conflict effect decreases and even reverses as mental rotation angles increase. Additionally, it was observed that participants responded more quickly and with greater accuracy to small rather than large face orientations. A comparison of three conflict diffusion models-the diffusion model for conflict tasks (DMC), the dual-stage two-phase model (DSTP), and the shrinking spotlight model (SSP)-yielded consistent support for the DSTP over the DMC and SSP in the majority of instances. The DSTP account of the experimental results revealed an increased nondecision time with increasing mental rotation, a reduction in interference from incompatible stimuli, and an improved drift rate in response selection phase, which suggests enhanced cognitive control. The findings from the model-based analysis provide evidence for a novel interaction between cognitive control and mental rotation.

PGD: Shared gene linking polycystic ovary syndrome and endometrial cancer, influencing proliferation and migration through glycometabolism.

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Validity of stem cell-loaded scaffolds to facilitate endometrial regeneration and restore fertility: a systematic review and meta-analysis.

Objective: Various stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models. Methods: The PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots. Results: Thirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = -2.50, 95% CI: -3.07 to -1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation. Conclusion: The evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.

The differential impact of face distractors on visual working memory across encoding and delay stages.

External distractions often occur when information must be retained in visual working memory (VWM)-a crucial element in cognitive processing and everyday activities. However, the distraction effects can differ if they occur during the encoding rather than the delay stages. Previous research on these effects used simple stimuli (e.g., color and orientation) rather than considering distractions caused by real-world stimuli on VWM. In the present study, participants performed a facial VWM task under different distraction conditions across the encoding and delay stages to elucidate the mechanisms of distraction resistance in the context of complex real-world stimuli. VWM performance was significantly impaired by delay-stage but not encoding-stage distractors (Experiment 1). In addition, the delay distraction effect arose primarily due to the absence of distractor process at the encoding stage rather than the presence of a distractor during the delay stage (Experiment 2). Finally, the impairment in the delay-distraction condition was not due to the abrupt appearance of distractors (Experiment 3). Taken together, these findings indicate that the processing mechanisms previously established for resisting distractions in VWM using simple stimuli can be extended to more complex real-world stimuli, such as faces.

Imitating and exploring the human brain's resting and task-performing states via brain computing: scaling and architecture.

A computational human brain model with the voxel-wise assimilation method was established based on individual structural and functional imaging data. We found that the more similar the brain model is to the biological counterpart in both scale and architecture, the more similarity was found between the assimilated model and the biological brain both in resting states and during tasks by quantitative metrics. The hypothesis that resting state activity reflects internal body states was validated by the interoceptive circuit's capability to enhance the similarity between the simulation model and the biological brain. We identified that the removal of connections from the primary visual cortex (V1) to downstream visual pathways significantly decreased the similarity at the hippocampus between the model and its biological counterpart, despite a slight influence on the whole brain. In conclusion, the model and methodology present a solid quantitative framework for a digital twin brain for discovering the relationship between brain architecture and functions, and for digitally trying and testing diverse cognitive, medical and lesioning approaches that would otherwise be unfeasible in real subjects.

Oscillating paramagnetic Meissner effect and Berezinskii-Kosterlitz-Thouless transition in underdoped Bi2Sr2CaCu2O8+δ.

Superconducting phase transitions in two dimensions lie beyond the description of the Ginzburg-Landau symmetry-breaking paradigm for three-dimensional superconductors. They are Berezinskii-Kosterlitz-Thouless (BKT) transitions of paired-electron condensate driven by the unbinding of topological excitations, i.e. vortices. The recently discovered monolayers of layered high-transition-temperature ([Formula: see text]) cuprate superconductor Bi2Sr2CaCu2O8+δ (Bi2212) meant that this 2D superconductor promised to be ideal for the study of unconventional superconductivity. But inhomogeneity posed challenges for distinguishing BKT physics from charge correlations in this material. Here, we utilize the phase sensitivity of scanning superconducting quantum interference device microscopy susceptometry to image the local magnetic response of underdoped Bi2212 from the monolayer to the bulk throughout its phase transition. The monolayer segregates into domains with independent phases at elevated temperatures below [Formula: see text]. Within a single domain, we find that the susceptibility oscillates with flux between diamagnetism and paramagnetism in a Fraunhofer-like pattern up to [Formula: see text]. The finite modulation period, as well as the broadening of the peaks when approaching [Formula: see text] from below, suggests well-defined vortices that are increasingly screened by the dissociation of vortex-antivortex plasma through a BKT transition. In the multilayers, the susceptibility oscillation differs in a small temperature regime below [Formula: see text], consistent with a dimensional crossover led by interlayer coupling. Serving as strong evidence for BKT transition in the bulk, we observe a sharp jump in phase stiffness and paramagnetism at small fields just below [Formula: see text]. These results unify the superconducting phase transitions from the monolayer to the bulk underdoped Bi2212, and can be collectively referred to as the BKT transition with interlayer coupling.

Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction.

Novel CHCHD2 mutations causing C-terminal truncation and interrupted CHCHD2 protein stability in Parkinson's disease (PD) patients were previously found. However, there is limited understanding of the underlying mechanism and impact of subsequent CHCHD2 loss-of-function on PD pathogenesis. The current study further identified the crucial motif (aa125-133) responsible for diminished CHCHD2 expression and the molecular interplay within the C1QBP/CHCHD2/CHCHD10 complex to regulate mitochondrial functions. Specifically, CHCHD2 deficiency led to decreased neural cell viability and mitochondrial structural and functional impairments, paralleling the upregulation of autophagy under cellular stresses. Meanwhile, as a binding partner of CHCHD2, C1QBP was found to regulate the stability of CHCHD2 and CHCHD10 proteins to maintain the integrity of the C1QBP/CHCHD2/CHCHD10 complex. Moreover, C1QBP-silenced neural cells displayed severe cell death phenotype along with mitochondrial damage that initiated a significant mitophagy process. Taken together, the evidence obtained from our in vitro and in vivo studies emphasized the critical role of CHCHD2 in regulating mitochondria functions via coordination among CHCHD2, CHCHD10, and C1QBP, suggesting the potential mechanism by which CHCHD2 function loss takes part in the progression of neurodegenerative diseases.