Effect of static pressure on ultrasonic liquid phase exfoliation of few-layer graphene.

Ultrasonic Liquid Phase Exfoliation (LPE) has gathered attention from both scientific and industrial communities for its accessibility and cost-effectiveness in producing graphene. However, this technique has faced challenges such as low yield and long production time. In this study, we developed a cyclic ultrasonication system to exfoliate expanded graphite (EG) by applying static pressure to a flow chamber to address these challenges. Using deionized water (DIW) as solvent and polyvinylpyrrolidone (PVP) as dispersion, we obtained graphene slurries with an average lateral size of 7 µm and averaged number of layers of 3.5 layers, after 40 min of ultrasonication. After centrifugation, the yield of single and bilayer graphene was approximately 16 %. The findings showed that regulating hydrostatic pressure can effectively affect the lateral size and number of layers of few-layer graphene. The proposed method is of good potential for scaled-up production of few-layer graphene.

Could early life DHA supplementation benefit neurodevelopment? A systematic review and meta-analysis.

Background: Docosahexaenoic acid (DHA) plays a crucial role in the growth and functional development of the infant brain. However, the impact of additional DHA supplementation on neurodevelopment in infants remains controversial in randomized controlled trials. In this systematic review and meta-analysis, we aimed to investigate the effects of prenatal and postnatal DHA supplementation on neurodevelopment. Methods: We systematically searched the MEDLINE, EMBASE, and Cochrane Library electronic databases using a predefined strategy until 8 February 2024. We extracted relevant study characteristics and outcomes related to the nervous system. Two independent reviewers critically evaluated the included studies to assess their validity and risk of bias. Results: A total of 21 studies met our inclusion criteria, one study was removed after quality assessment, and the meta-analysis included 9 randomized controlled trials. The meta-analysis results indicated that there was no statistically significant difference between the DHA supplementation group and the placebo group, as assessed by the Mental Development Index [MDI; mean difference (MD), 0.41; 95% confidence interval (CI), -0.91 to 1.73; p = 0.55]. However, the DHA group had a significantly higher Psychomotor Development Index (PDI) than the placebo group (MD, 1.47; 95% CI, 0.23 to 2.72; p = 0.02). Subgroup analyses based on populations showed that DHA supplementation was superior to placebo for infants in both MDI (language score conversion; MD, 2.05; 95% CI, -0.16 to 4.26; p = 0.07) and PDI (MD, 1.94; 95% CI, 0.23 to 3.65; p = 0.03). Other subgroup analyses indicated no statistical differences between the two groups. The remaining assessments that could not be summarized quantitatively underwent a narrative evaluation. Conclusion: Based on the BSID assessments, DHA supplementation in infants may have potential neurodevelopmental benefits. Because the meta-analysis included few high-quality articles and had some limitations, more relevant articles are needed to address the need for separate DHA supplementation in infants, pregnant women, and lactating mothers. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022348100, identifier: CRD42022348100.

Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma.

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, qPCR and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2 and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2 and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A and IL-18 in AA patients were elevated, and they were correlated between each other. In OVA-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2 and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/-mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.

Recent advances in age-related metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 25% of the world's population and has become a leading cause of chronic liver disease. In recent years, an increasing amount of data suggests that MASLD is associated with aging. As the population ages, age-related MASLD will become a major global health problem. Targeting an aging will become a new approach to the treatment of MASLD. This paper reviews the current studies on the role of aging-related factors and therapeutic targets in MASLD, including: Oxidative stress, autophagy, mitochondrial homeostasis, bile acid metabolism homeostasis, and dysbiosis. The aim is to identify effective therapeutic targets for age-related MASLD and its progression.

Abnormal amplitude of low-frequency fluctuations associated with sleep efficiency in major depressive disorder.

BACKGROUND: Sleep disturbance is one of the most frequent somatic symptoms in major depressive disorder (MDD), but the neural mechanisms behind it are not well understood. Sleep efficiency (SE) is a good indicator of early awakening and difficulty falling asleep in MDD patients. Our study aimed to investigate the relationship between sleep efficiency and brain function in MDD patients. METHODS: We recruited 131 MDD patients from the Fourth People's Hospital in Hefei, and 71 well-matched healthy controls who were enrolled from the community. All subjects underwent resting-state functional MRI. Brain function was measured using the fractional amplitude of low-frequency fluctuation (fALFF), sleep efficiency was objectively measured by polysomnography (PSG), and clinical scales were used to evaluate depressive symptoms and sleep status. Multivariate regression analysis was performed to assess the relationship between the amplitude of the low frequency fluctuation fraction and sleep efficiency. RESULT: Three brain regions with relevance to sleep efficiency in MDD patients were found: inferior occipital gyrus (Number of voxels = 25, peak MNI coordinate x/y/z = -42/-81/-6, Peak intensity = 4.3148), middle occipital gyrus (Number of voxels = 55, peak MNI coordinate x/y/z = -30/-78/18, Peak intensity = 5.111), and postcentral gyrus (Number of voxels = 26, peak MNI coordinate x/y/z = -27/-33/60, Peak intensity = 4.1263). But there was no significant relationship between fALFF and SE in the healthy controls. CONCLUSION: The reduced sleep efficiency in MDD may be related to their lower neural activity in the inferior occipital gyrus, middle occipital gyrus, and postcentral gyrus. The findings may provide a potential neuroimaging basis for the clinical intervention in patients with major depressive disorder with sleep disturbances.

Design and Effect of Resonant Ultrasonic Vibration-Assisted Laser Cladding (R-UVALC) on AlCrFeMnNi High-Entropy Alloy.

The design of the resonant ultrasonic vibration-assisted laser cladding (R-UVALC) setup involved employing finite element analysis (FEA) to simulate the ultrasonic transducer, horn, and workpiece in a resonance state. The impact of R-UVALC on AlCrFeMnNi high-entropy alloys was assessed using various ultrasonic vibration amplitudes of 0, 5, 10, and 15 µm, with a constant frequency of 20 kHz. Ultrasonic vibrations reduced pores and cracks and increased the clad breadth, melt pool wetting angle, and laser-clad layer consistency. The columnar elongated grains in proximity to the substrate surface underwent a size reduction and transformed into grains with a more equiaxed shape with the utilization of ultrasonic vibrations at an amplitude of 5 µm. Laser cladding performed without ultrasonic vibrations yields two phases: face-centered cubic (FCC) and body-centered cubic (BCC). However, when the coating is exposed to ultrasonic vibrations with an amplitude of 5 µm, it forms a solitary body-centered cubic (BCC) phase. The microhardness tripled compared to the substrate, and the most significant microhardness value was achieved at 5 µm of ultrasonic vibration. The friction coefficient was assessed at an ambient temperature, revealing that an ultrasonic amplitude yields the lowest friction coefficient, demonstrating the excellent wear resistance properties of the coating. The analysis of the 3D surface profile of the wear indicates that the use of ultrasonic aid with a 5 µm amplitude leads to reduced depth of scars, and the primary wear mechanism observed is abrasive and oxidative wear with fewer grooves and debris. In addition, XPS analysis revealed the presence of metal components in an oxidized condition, suggesting that the wear process is oxidative in nature. Integrating the R-UVALC setup into a resonance state can significantly enhance the efficiency of the laser cladding process in the laser cladding field.

Photoredox-Catalyzed Alkene Amination: C(sp2)-H/N-H Radical-Radical Cross Dehydrogenative Coupling.

Direct alkene C-H/N-H cross dehydrogenative coupling is an infrequent, highly challenging transformation. Herein, a photoredox radical-radical cross-coupling reaction between ketene dithioacetal as a persistent alkene radical cation and azole nitrogen center radical (NCR) was developed. This direct alkene amination proceeded through a synergistic photoredox and cobalt catalysis, with only H2 evolution. The reaction showed excellent tolerance and highly regio- and stereospecific manner, expanding the scope of C(sp2)-N construction methods and radical cross-coupling modes.

Efficient Photothermal Catalytic Oxidation Enabled by Three-Dimensional Nanochannel Substrates.

Photothermal catalysis exhibits promising prospects to overcome the shortcomings of high-energy consumption of traditional thermal catalysis and the low efficiency of photocatalysis. However, there is still a challenge to develop catalysts with outstanding light absorption capability and photothermal conversion efficiency for the degradation of atmospheric pollutants. Herein, we introduced the Co3O4 layer and Pt nanoclusters into the three-dimensional (3D) porous membrane through the atomic layer deposition (ALD) technique, leading to a Pt/Co3O4/AAO monolithic catalyst. The 3D ordered nanochannel structure can significantly enhance the solar absorption capacity through the light-trapping effect. Therefore, the embedded Pt/Co3O4 catalyst can be rapidly heated and the O2 adsorbed on the Pt clusters can be activated to generate sufficient O2- species, exhibiting outstanding activity for the diverse VOCs (toluene, acetone, and formaldehyde) degradation. Optical characterization and simulation calculation confirmed that Pt/Co3O4/AAO exhibited state-of-the-art light absorption and a notable localized surface plasmon resonance (LSPR) effect. In situ diffuse reflectance infrared Fourier transform spectrometry (in situ DRIFTS) studies demonstrated that light irradiation can accelerate the conversion of intermediates during toluene and acetone oxidation, thereby inhibiting byproduct accumulation. Our finding extends the application of AAO's optical properties in photothermal catalytic degradation of air pollutants.

Nitrogen-doped substrate material ion imprinting-capacitive deionization selective recovery of lithium ions from acidic solutions.

With the continuous development of global industry and the increasing demand for lithium resources, recycling valuable lithium from industrial solid waste is necessary for sustainable development and environmental friendliness. Herein, we employed ion imprinting and capacitive deionization to prepare a new electrode material for lithium-ion selective recovery. The material morphology and structure were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, and other characterization methods, and the adsorption mechanism and water clusters were correlated using the density functional theory. The electrode material exhibited a maximum adsorption capacity of 36.94 mg/g at a Li+ concentration of 600 mg/L. The selective separation factors for Na+, K+, Mg2+, and Al3+ in complex solution environments were 2.07, 9.82, 1.80, and 8.45, respectively. After undergoing five regeneration cycles, the material retained 91.81% of the initial Li+ adsorption capacity. Meanwhile, the electrochemical adsorption capacity for Li+ was more than twice the corresponding conventional physical adsorption capacity because electrochemical adsorption provides the energy needed for deprotonation, enabling exposure of the cavities of the crown ether molecules to enrich the active sites. The proposed environment-friendly separation approach offers excellent selectivity for Li+ recovery and addresses the growing demand for Li+ resources.

LncRNA-SNHG5 mediates activation of hepatic stellate cells by regulating NF2 and Hippo pathway.

Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is an oncogene found in various human cancers. However, it is unclear what role SNHG5 plays in activating hepatic stellate cells (HSCs) and liver fibrosis. In this study, SNHG5 was found to be upregulated in activated HSCs in vitro and in primary HSCs isolated from fibrotic liver in vivo, and inhibition of SNHG5 suppressed HSC activation. Notably, Neurofibromin 2 (NF2), the main activator for Hippo signalling, was involved in the effects of SNHG5 on HSC activation. The interaction between SNHG5 and NF2 protein was further confirmed, and preventing the combination of the two could effectively block the effects of SNHG5 inhibition on EMT process and Hippo signaling. Additionally, higher SNHG5 was found in chronic hepatitis B patients and associated with the fibrosis stage. Altogether, we demonstrate that SNHG5 could serve as an activated HSCs regulator via regulating NF2 and Hippo pathway.

Mediodorsal thalamus projection to medial prefrontal cortical mediates social defeat stress-induced depression-like behaviors.

Clinical studies have shown that the mediodorsal thalamus (MD) may play an important role in the development of depression. However, the molecular and circuit mechanisms by which the mediodorsal thalamus (MD) participates in the pathological processes of depression remain unclear. Here, we show that in male chronic social defeat stress (CSDS) mice, the calcium signaling activity of glutamatergic neurons in MD is reduced. By combining conventional neurotracer and transneuronal virus tracing techniques, we identify a synaptic circuit connecting MD and medial prefrontal cortex (mPFC) in the mouse. Brain slice electrophysiology and fiber optic recordings reveal that the reduced activity of MD glutamatergic neurons leads to an excitatory-inhibitory imbalance of pyramidal neurons in mPFC. Furthermore, activation of MD glutamatergic neurons restores the electrophysiological properties abnormal in mPFC. Optogenetic activation of the MD-mPFC circuit ameliorates anxiety and depression-like behaviors in CSDS mice. Taken together, these data support the critical role of MD-mPFC circuit on CSDS-induced depression-like behavior and provide a potential mechanistic explanation for depression.

A novel compound heterozygous variant of ECEL1 induced joint dysfunction and cartilage degradation: a case report and literature review.

Background: Distal arthrogryposis type 5D (DA5D) represents a subtype of distal arthrogryposis (DA) characterized by congenital joint contractures in the distal extremities. DA5D is inherited in a rare autosomal recessive manner and is associated with the ECEL1 gene. In this report, we describe a case of an infant with bilateral knee contractures and ptosis, caused by a novel compound heterozygous mutation of ECEL1. Case presentation: We conducted DNA extraction, whole-exome sequencing analysis, and mutation analysis of ECEL1 to obtain genetic data on the patient. We subsequently analyzed the patient's clinical and genetic data. The proband was a 6 months-old male infant who presented with significant bilateral knee contracture disorders and bilateral ptosis. MRI demonstrated cartilage degradation in knee joint. Whole-exome sequencing of the patient's DNA revealed a compound heterozygous mutation of c.2152-15C>A and c.110_155del in ECEL1. Analysis with the MutationTaster application indicated that c.110_155del was pathogenic (probability = 1), causing frameshift mutations affecting 151 amino acids (p.F37Cfs*151). The truncated protein lost the substructure of a transmembranous site based on the predicted protein crystal structure AF-O95672-F1. The variant of c.2152-15C>A of ECEL1 was also predicted to be disease-causing (probability = 0.98) as it impaired the methylation of ECEL1 serving as an H3K27me3 modification site, which led to the dysfunction of the second topological domain. Therefore, we concluded that the compound heterozygous mutation caused the pathogenic phenotype of this proband. Conclusion: The present case highlights the usefulness of molecular genetic screening in diagnosing unexpected joint disorder. Identification of novel mutations in the ECEL1 gene broadens the mutation spectrum of this gene and adds to the genotype-phenotype map of DA5D. Furthermore, rapid whole-exome sequencing analysis enabled timely diagnosis of this rare disease, facilitating appropriate treatment and scheduled follow-up to improve clinical outcomes.

A comprehensive review of various carbonaceous materials for anodes in lithium-ion batteries.

With the advent of lithium-ion batteries (LIBs), the selection and application of electrode materials have been the subject of much discussion and study. Among them, graphite has been widely investigated for use as electrode materials in LIBs due to its abundant resources, low cost, safety and electrochemical diversity. While it is commonly recognized that conventional graphite materials utilized for commercial purposes have a limited theoretical capacity, there has been a steady emergence of new and improved carbonaceous materials for use as anodes in light of the progressive development of LIBs. In this paper, the latest research progress of various carbon materials in LIBs is systematically and comprehensively reviewed. Firstly, the rocking chair charging and discharging mechanism of LIBs is briefly introduced in this paper, using graphite anodes as an example. After that, the general categories of carbonaceous materials are highlighted, and the recent research on the recent progress of various carbonaceous materials (graphite-based, amorphous carbon-based, and nanocarbon-based) used in LIB anodes is presented separately based on the classification of the structural morphology, emphasizing the influence of the morphology and structure of carbon-based materials on the electrochemical performance of the batteries. Finally, the current challenges of carbonaceous materials in LIB applications and the future development of other novel carbonaceous materials are envisioned.

Identification of two hub genes and miRNA­mRNA interactions in chronic obstructive pulmonary disease (COPD) plasma.

BACKGROUND: We aimed to identify hub genes in chronic obstructive pulmonary disease (COPD) plasma through the exploration of a putative miRNA-mRNA regulatory network. METHODS: Three datasets (GSE24709, GSE102915, GSE136390) were utilized to discern differentially expressed miRNAs (DEMs) between COPD and normal plasma. miRNET was employed to predict the potential targets of DEMs. Subsequent GO and KEGG analyses were conducted using DAVID. For the construction of the protein-protein interaction (PPI) network and screening of hub genes, STRING and Cytoscape were employed. The expression validation was assessed through GSE56768. RESULTS: The results revealed 395 genes targeted by up-regulated DEMs and 234 genes targeted by down-regulated DEMs. The target genes exhibited significant enrichment in the PI3K-Akt signaling pathway and the p53 signaling pathway. Through the validation of hub genes' expression, we proposed two potential miRNA-mRNA interactions: miR-126-5p/miR-495-3p/miR-193b-3p - YWHAZ and miR-937-5p/miR-183-5p/miR-34c-5p/miR-98-5p/miR-525-3p/miR-215-5p - ACTB. CONCLUSIONS: In conclusion, our study posits potential miRNA-mRNA interactions in COPD by analyzing datasets from public databases, contributing valuable insights into the understanding of COPD pathogenesis and potential therapeutic avenues.

Circadian rhythms of melatonin and its relationship with anhedonia in patients with mood disorders: a cross-sectional study.

BACKGROUND: Mood disorders are strongly associated with melatonin disturbances. However, it is unclear whether there is a difference in melatonin concentrations and melatonin circadian rhythm profiles between depression and bipolar disorder. In addition, the relationship between anhedonia, a common symptom of affective disorders, and its melatonin circadian rhythm remains under-investigated. METHODS: Thirty-four patients with depression disorder, 20 patients diagnosed with bipolar disorder and 21 healthy controls participated in this study. The Revised Physical Anhedonia Scale (RPAS) was performed to assess anhedonia. Saliva samples were collected from all subjects at fixed time points (a total of 14 points) in two consecutive days for measuring the melatonin concentrations to fit circadian rhythms of subjects. Melatonin circadian rhythms were compared between the three groups using ANOVA. Partial correlation analysis and linear regression analysis were used to explore the correlation between melatonin rhythm variables and anhedonia. RESULTS: We found that the peak phase of melatonin in the depression group was significantly advanced compared to the control group (P < 0.001) and the bipolar disorder group (P = 0.004). The peak phase of melatonin and RPAS showed a negative correlation (P = 0.003) in depression patients, which was also demonstrated in the multiple linear regression model (B=-2.47, P = 0.006). CONCLUSIONS: These results suggest that circadian rhythms of melatonin are differentiated in depression and bipolar disorder and correlate with anhedonia in depression. Future research needs to explore the neurobiological mechanisms linking anhedonia and melatonin circadian rhythms in depressed patients.

Mendelian randomization analysis demonstrates the causal effects of IGF family members in diabetes.

Background: Observational studies have consistently shown significant associations between the IGF family and metabolic diseases, including diabetes. However, these associations can be influenced by confounding factors and reverse causation. This study aimed to assess the causal relationship between the IGF family and diabetes using Mendelian randomization (MR). Methods: We conducted a two-sample MR analysis to investigate the causal effects of the IGF family on diabetes. Instrumental variables for the IGF family and diabetes were derived from summary-level statistics obtained from genome-wide association studies. Horizontal pleiotropy was assessed using MR-Egger regression and the weighted median method. We applied the inverse-variance weighted method as part of the conventional MR analysis to evaluate the causal impact of the IGF family on diabetes risk. To test the robustness of the results, we also employed MR-Egger regression, the weighted median method, and a leave-one-out analysis. Results: Our study revealed that IGF-1 causally increases the risk of Type 2 Diabetes (T2D), while IGFBP-6, adiponectin and INSR decreases the risk (IGF-1, OR 1.02 [95% CI 1-1.03], p = 0.01; IGFBP-6, OR 0.92 [95% CI 0.87-0.98], p = 0.01; Adiponectin, OR 0.837 [95% CI 0.721-0.970], p = 0.018; INSR, OR 0.910 [95% CI 0.872-0.950], p = 1.52 × 10-5). Additionally, genetically lower levels of IGF-1 and IGFBP-5, along with higher levels of IGFBP-7, were associated with an increased risk of Type 1 Diabetes (T1D) (IGF-1, OR 0.981 [95% CI 0.963-0.999], p = 0.037; IGFBP-5, OR 0.882 [95% CI 0.778-0.999], p = 0.049; IGFBP-7, OR 1.103 [95% CI 1.008-1.206], p = 0.033). Conclusion: In summary, our investigation has unveiled causal relationships between specific IGF family members and T1D and T2D through MR analysis. Generally, the IGF family appears to reduce the risk of T1D, but it presents a more complex and controversial role in the context of T2D. These findings provide compelling evidence that T2D is intricately linked with developmental impairment. Our study results offer fresh insights into the pathogenesis and the significance of serum IGF family member concentrations in assessing diabetes risk.

Hierarchical Capability in Distinguishing Severities of Sepsis via Serum Lactate: A Network Meta-Analysis.

Background: Blood lactate is a potentially useful biomarker to predict the mortality and severity of sepsis. The purpose of this study is to systematically review the ability of lactate to predict hierarchical sepsis clinical outcomes and distinguish sepsis, severe sepsis and septic shock. Methods: We conducted an exhaustive search of the PubMed, Embase and Cochrane Library databases for studies published before 1 October 2022. Inclusion criteria mandated the presence of case-control, cohort studies and randomized controlled trials that established the association between before-treatment blood lactate levels and the mortality of individuals with sepsis, severe sepsis or septic shock. Data was analyzed using STATA Version 16.0. Results: A total of 127 studies, encompassing 107,445 patients, were ultimately incorporated into our analysis. Meta-analysis of blood lactate levels at varying thresholds revealed a statistically significant elevation in blood lactate levels predicting mortality (OR = 1.57, 95% CI 1.48-1.65, I2 = 92.8%, p < 0.00001). Blood lactate levels were significantly higher in non-survivors compared to survivors in sepsis patients (SMD = 0.77, 95% CI 0.74-0.79, I2 = 83.7%, p = 0.000). The prognostic utility of blood lactate in sepsis mortality was validated through hierarchical summary receiver operating characteristic curve (HSROC) analysis, yielding an area under the curve (AUC) of 0.72 (95% CI 0.68-0.76), accompanied by a summary sensitivity of 0.65 (95% CI 0.59-0.7) and a summary specificity of 0.7 (95% CI 0.64-0.75). Unfortunately, the network meta-analysis could not identify any significant differences in average blood lactate values' assessments among sepsis, severe sepsis and septic shock patients. Conclusions: This meta-analysis demonstrated that high-level blood lactate was associated with a higher risk of sepsis mortality. Lactate has a relatively accurate predictive ability for the mortality risk of sepsis. However, the network analysis found that the levels of blood lactate were not effective in distinguishing between patients with sepsis, severe sepsis and septic shock.

Precise genome-editing in human diseases: mechanisms, strategies and applications.

Precise genome-editing platforms are versatile tools for generating specific, site-directed DNA insertions, deletions, and substitutions. The continuous enhancement of these tools has led to a revolution in the life sciences, which promises to deliver novel therapies for genetic disease. Precise genome-editing can be traced back to the 1950s with the discovery of DNA's double-helix and, after 70 years of development, has evolved from crude in vitro applications to a wide range of sophisticated capabilities, including in vivo applications. Nonetheless, precise genome-editing faces constraints such as modest efficiency, delivery challenges, and off-target effects. In this review, we explore precise genome-editing, with a focus on introduction of the landmark events in its history, various platforms, delivery systems, and applications. First, we discuss the landmark events in the history of precise genome-editing. Second, we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome. Third, we introduce the current delivery systems used to deploy precise genome-editing components through DNA, RNA, and RNPs. Finally, we summarize the current applications of precise genome-editing in labeling endogenous genes, screening genetic variants, molecular recording, generating disease models, and gene therapy, including ex vivo therapy and in vivo therapy, and discuss potential future advances.

CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.

Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4low and CXCR4high groups were selected for RNASeq analysis. The progression-free survival (PFS) of CLL patients in the CXCR4high group was significantly shorter than the CXCR4low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of RNASeq results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.

Potential Roles of Nr4a3-Mediated Inflammation in Immunological and Neurological Diseases.

As a protein of the orphan nuclear receptor Nr4a family, Nr4a3 has no identified natural ligands. However, its biological activity can be mediated by inducing conformational changes through interactions with specific certain small molecules and receptors. Nr4a3 is activated as an early stress factor under various pathological conditions and plays a regulatory role in various tissues and cells, participating in processes such as cell differentiation, apoptosis, metabolism, and homeostasis. At present, research on the role of Nr4a3 in the pathophysiology of inflammation is considerably limited, especially with respect to its role in the central nervous system (CNS). In this review, we discuss the role of Nr4a3 in multiple sclerosis, Alzheimer's disease, retinopathy, Parkinson's disease, and other CNS diseases. This review shows that Nr4a3 has considerable potential as a therapeutic target in the treatment of CNS diseases. We provide a theoretical basis for the targeted therapy of CNS diseases and neuroinflammation, among other conditions.