Sub-MIC antibiotics increased the fitness cost of CRISPR-Cas in Acinetobacter baumannii.

Introduction: The escalating prevalence of bacterial resistance, particularly multidrug-resistant bacteria like Acinetobacter baumannii, has become a significant global public health concern. The CRISPR-Cas system, a crucial defense mechanism in bacteria against foreign genetic elements, provides a competitive advantage. Type I-Fb and Type I-Fa are two subtypes of CRISPR-Cas systems that were found in A. baumannii, and the I-Fb CRISPR-Cas system regulates antibiotic resistance in A. baumannii. However, it is noteworthy that a majority of clinical isolates of A. baumannii lack or have incomplete CRISPR-Cas systems and most of them are multidrug-resistant. In light of this, our study aimed to examine the impact of antibiotic pressure on the fitness cost of the I-Fb CRISPR-Cas system in A. baumannii. Methods and Results: In the study, we conducted in vitro competition experiments to investigate the influence of sub-minimum inhibitory concentration (sub-MIC) on the CRISPR-Cas systems' fitness cost in A. baumannii. We found that the fitness cost of the CRISPR-Cas system was increased under sub-MIC conditions. The expression of CRISPR-Cas-related genes was decreased, while the conjugation frequency was increased in AB43 under sub-MIC conditions. Through metabolomic analysis, we identified that sub-MIC conditions primarily affected energy metabolism pathways. In particular, we observed increased carbon metabolism, nitrogen metabolism, and intracellular ATP. Notably, the CRISPR-Cas system demonstrated resistance to the efflux pump-mediated resistance. Furthermore, the expression of efflux pump-related genes was increased under sub-MIC conditions. Conclusion: Our findings suggest that the I-Fb CRISPR-Cas system confers a significant competitive advantage in A. baumanni. However, under sub-MIC conditions, its function and the ability to inhibit the energy required for efflux pumps are reduced, resulting in an increased fitness cost and loss of competitive advantage.

Roles of non-coding RNA in diabetic cardiomyopathy.

In recent years, the incidence of diabetes has been increasing rapidly, posing a serious threat to human health. Diabetic cardiomyopathy (DCM) is characterized by cardiomyocyte hypertrophy, myocardial fibrosis, apoptosis, ventricular remodeling, and cardiac dysfunction in individuals with diabetes, ultimately leading to heart failure and mortality. However, the underlying mechanisms contributing to DCM remain incompletely understood. With advancements in molecular biology technology, accumulating evidence has shown that numerous non-coding RNAs (ncRNAs) crucial roles in the development and progression of DCM. This review aims to summarize recent studies on the involvement of three types of ncRNAs (micro RNA, long ncRNA and circular RNA) in the pathophysiology of DCM, with the goal of providing innovative strategies for the prevention and treatment of DCM.

FERMT1 suppression induces anti-tumor effects and reduces stemness in glioma cancer cells.

OBJECTIVE: Glioma is a leading cause of mortality worldwide, its recurrence poses a major challenge in achieving effective treatment outcomes. Cancer stem cells (CSCs) have emerged as key contributors to tumor relapse and chemotherapy resistance, making them attractive targets for glioma cancer therapy. This study investigated the potential of FERMT1 as a prognostic biomarker and its role in regulating stemness through cell cycle in glioma. METHODS: Using data from TCGA-GBM, GSE4290, GSE50161 and GSE147352 for analysis of FERMT1 expression in glioma tissues. Then, the effects of FERMT1 knockdown on cell cycle, proliferation, sphere formation ability, invasion and migration were investigated. The influences of FERMT1 on expression of glycolysis-related proteins and levels of ATP, glucose, lactate and G6PDH were also explored. Furthermore, the effects of FERMT1 knockdown on cellular metabolism were evidenced. RESULTS: Significant upregulation of FERMT1 in glioma tissues was observed. Silencing FERMT1 not only affected the cell cycle but also led to a notable reduction in proliferation, invasion and migration. The expression of glycolysis-associated proteins including GLUT1, GLUT3, GLUT4, and SCO2 were reduced by FERMT1 knockdown, resulted in increased ATP and glucose as well as decreased lactic acid and G6PDH levels. FERMT1 knockdown also inhibited cellular metabolism. Moreover, FERMT1 knockdown significantly reduced sphere diameter, along with inhibiting the expression of transcription factors associated with stemness in glioma cells. CONCLUSION: These findings demonstrated that FERMT1 could be an ideal target for the advancement of innovative strategies against glioma treatment via modulating cellular process involved in stemness regulation and metabolism.

Association among internalizing problems, white matter integrity, and social difficulties in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by social difficulties and often accompanied by internalizing and externalizing problems, which are frequently overlooked. Here, we examined and compared fractional anisotropy (FA) between 79 children with ASD (aged 4-7.8 years) and 70 age-, gender-, and handedness- matched typically developing controls (TDCs, aged 3-7.2 years). We aimed to explore the relationship among social difficulties, internalizing and externalizing problems, and brain structural foundation (characterized by white matter integrity). Compared with the TDCs, the children with ASD exhibited more severe internalizing and externalizing problems, which were positively correlated with social difficulties. Reduced FA values were observed in specific white matter tracts that integrate a fronto-temporal-occipital circuit. In particular, the FA values within this circuit were negatively correlated with internalizing problems and SRS-TOTAL scores. Mediation analysis revealed that internalizing problems mediated the relationship between the FA values in the left middle longitudinal fasciculus (L-MdLF) and corpus callosum forceps major (CCM) and social difficulties in children with ASD. These findings contribute to our understanding of social difficulties, internalizing and externalizing problems, and white matter integrity in children with ASD and highlight internalizing problems as a mediator between social difficulties and white matter integrity.

Unveiling candidate genes for metabolic resistance to malathion in Aedes albopictus through RNA sequencing-based transcriptome profiling.

Aedes albopictus, also known as the Asian tiger mosquito, is indigenous to the tropical forests of Southeast Asia. Ae. albopictus is expanding across the globe at alarming rates, raising concern over the transmission of mosquito-borne diseases, such as dengue, West Nile fever, yellow fever, and chikungunya fever. Since Ae. albopictus was reported in Houston (Harris County, Texas) in 1985, this species has rapidly expanded to at least 32 states across the United States. Public health efforts aimed at controlling Ae. albopictus, including surveillance and adulticide spraying operations, occur regularly in Harris County. Despite rotation of insecticides to mitigate the development of resistance, multiple mosquito species including Culex quinquefasciatus and Aedes aegypti in Harris County show organophosphate and pyrethroid resistance. Aedes albopictus shows relatively low resistance levels as compared to Ae. aegypti, but kdr-mutation and the expression of detoxification genes have been reported in Ae. albopictus populations elsewhere. To identify potential candidate detoxification genes contributing to metabolic resistance, we used RNA sequencing of field-collected malathion-resistant and malathion-susceptible, and laboratory-maintained susceptible colonies of Ae. albopictus by comparing the relative expression of transcripts from three major detoxification superfamilies involved in malathion resistance due to metabolic detoxification. Between these groups, we identified 12 candidate malathion resistance genes and among these, most genes correlated with metabolic detoxification of malathion, including four P450 and one alpha esterase. Our results reveal the metabolic detoxification and potential cuticular-based resistance mechanisms associated with malathion resistance in Ae. albopictus in Harris County, Texas.

Tree-Inspired Structurally Graded Aerogel with Synergistic Water, Salt, and Thermal Transport for High-Salinity Solar-Powered Evaporation.

Solar-powered interfacial evaporation is an energy-efficient solution for water scarcity. It requires solar absorbers to facilitate upward water transport and limit the heat to the surface for efficient evaporation. Furthermore, downward salt ion transport is also desired to prevent salt accumulation. However, achieving simultaneously fast water uptake, downward salt transport, and heat localization is challenging due to highly coupled water, mass, and thermal transport. Here, we develop a structurally graded aerogel inspired by tree transport systems to collectively optimize water, salt, and thermal transport. The arched aerogel features root-like, fan-shaped microchannels for rapid water uptake and downward salt diffusion, and horizontally aligned pores near the surface for heat localization through maximizing solar absorption and minimizing conductive heat loss. These structural characteristics gave rise to consistent evaporation rates of 2.09 kg m-2 h-1 under one-sun illumination in a 3.5 wt% NaCl solution for 7 days without degradation. Even in a high-salinity solution of 20 wt% NaCl, the evaporation rates maintained stable at 1.94 kg m-2 h-1 for 8 h without salt crystal formation. This work offers a novel microstructural design to address the complex interplay of water, salt, and thermal transport.

Full C- and L-band covered second-order OAM mode generator based on a thinned helical long-period fiber grating.

A full C- and L-band covered second-order orbital-angular-momentum (OAM) mode generator has been proposed and experimentally demonstrated, which is realized by using a helical long-period fiber grating (HLPG) but inscribed in a thinned four-mode fiber. By optimizing the design of grating period and fiber diameter of the proposed HLPG, an ultra-broadband rejection filter with a depth of ∼23 dB, a bandwidth of ∼156 nm @-10 dB (ranging from 1522 nm to 1678 nm) and a bandwidth of ∼58 nm @-20 dB (ranging from 1574 nm to 1632 nm), has been successfully obtained as a typical sample. To the best of our knowledge, this is the first demonstration of such ultra-broadband second-order OAM mode generator by using only one fiber component, i.e., the thinned HLPG. In addition, the proposed generator is less polarization-dependent and less temperature-sensitive than those of the conventional HLPGs, which is believed to be considerably helpful to find potential applications of the device itself in wavelength division multiplexing (WDM) and OAM mode division multiplexing (MDM) optical fiber communication systems.

Atypical dynamic neural configuration in autism spectrum disorder and its relationship to gene expression profiles.

Although it is well recognized that autism spectrum disorder (ASD) is associated with atypical dynamic functional connectivity patterns, the dynamic changes in brain intrinsic activity over each time point and the potential molecular mechanisms associated with atypical dynamic temporal characteristics in ASD remain unclear. Here, we employed the Hidden Markov Model (HMM) to explore the atypical neural configuration at every scanning time point in ASD, based on resting-state functional magnetic resonance imaging (rs-fMRI) data from the Autism Brain Imaging Data Exchange. Subsequently, partial least squares regression and pathway enrichment analysis were employed to explore the potential molecular mechanism associated with atypical neural dynamics in ASD. 8 HMM states were inferred from rs-fMRI data. Compared to typically developing, individuals on the autism spectrum showed atypical state-specific temporal characteristics, including number of states and occurrences, mean life time and transition probability between states. Moreover, these atypical temporal characteristics could predict communication difficulties of ASD, and states assoicated with negative activation in default mode network and frontoparietal network, and positive activation in somatomotor network, ventral attention network, and limbic network, had higher predictive contribution. Furthermore, a total of 321 genes was revealed to be significantly associated with atypical dynamic brain states of ASD, and these genes are mainly enriched in neurodevelopmental pathways. Our study provides new insights into characterizing the atypical neural dynamics from a moment-to-moment perspective, and indicates a linkage between atypical neural configuration and gene expression in ASD.

Double Droplets Impact an Inclined Superhydrophobic Surface.

The rebound dynamics of double droplets impacting an inclined superhydrophobic surface decorated with macro-ridges are investigated via lattice Boltzmann method (LBM) simulations. Four rebound regions are identified, that is, the no-coalescence-rebound (NCR), the partial-coalescence-rebound of the middle part bounces first (PCR-M), and the side part bounces first (PCR-S), as well as the complete-coalescence-rebound (CCR). The occurrence of the rebound regions strongly depends on the droplet arrangement, the center-to-center distance of the droplets, and the Weber number. Furthermore, the contact time is closely related to the rebound regions. The PCR-M region can significantly reduce the contact time because the energy dissipation in this region may decrease which can promote the rebound dynamic. Intriguingly, the contact time is also affected by the droplet arrangement; i.e., droplets arranged parallel to the ridge dramatically shorten the contact time since this arrangement increases the asymmetry of the liquid film. Therefore, for multidrop impact, the contact time can be effectively manipulated by changing the rebound region and the droplet arrangement. This work focuses on elucidating the wetting behaviors, rebound regions, and contact time of the multiple-droplet impacting an inclined superhydrophobic surface decorated with macro-ridges.

Immunosuppressive alkaloids from Narcissus tazetta subsp. Chinensis and the mechanism of (+)-narciclasine in vitro and in vivo.

Three previously undescribed and sixteen known alkaloids were bioguidedly isolated from the bulbs of Narcissus tazetta subsp. chinensis (M.Roem.) Masamura & Yanagih. The structures were elucidated by spectroscopic data, including HRESIMS, NMR, and ECD. Eleven of the isolated alkaloids exhibited immunosuppressive activity on the proliferation of human T cells. (+)-Narciclasine (18) showed the most significantly suppressive activity with an IC50 value of 14 ± 5 nM. In vitro, (+)-narciclasine (18) blocked NF-κB signal transduction, but did not affect PI3K/AKT signal transduction. What was more, (+)-narciclasine significantly reduced ALT and AST levels and alleviated liver damage induced by ConA in AIH mouse model.

Corrigendum: The possibility of clinical bonding between metal/ceramic brackets to zirconia: in vitro study.

[This corrects the article DOI: 10.3389/fbioe.2024.1354241.].

Identification and function analysis of BCL2 in immune response of Pteria penguin.

B-cell lymphoma/leukemia-2 (BCL2), an anti-apoptotic factor in the mitochondrial regulatory pathway of apoptosis, is critically important in immune defenses. In this study, a novel BCL2 gene was characterized from Pteria penguin (P. penguin). The PpBCL2 was 1482 bp long, containing an open reading frame (ORF) of 588 bp encoding 195 amino acids. Four highly conserved BCL-2 homology (BH) domains were found in PpBCL2. Amino acid alignment and phylogenetic tree showed that PpBCL2 had the highest similarity with BCL2 of Crassostrea gigas at 65.24 %. Tissue expression analysis showed that PpBCL2 had high constitutive expression in gill, digestive diverticulum and mantle, and was significantly increased 72 h of Vibrio parahaemolyticus (V. parahaemolyticus) challenge in these immune tissues. Furthermore, PpBCL2 silencing significantly inhibited antimicrobial activity of hemolymph supernatant by 1.4-fold, and significantly reduced the survival rate by 51.7 % at 72 h post infection in P. penguin. These data indicated that PpBCL2 played an important role in immune response of P. penguin against V. parahaemolyticus infection.

Sea Cucumber-Inspired Microneedle Nerve Guidance Conduit for Synergistically Inhibiting Muscle Atrophy and Promoting Nerve Regeneration.

Muscle atrophy resulting from peripheral nerve injury (PNI) poses a threat to a patient's mobility and sensitivity. However, an effective method to inhibit muscle atrophy following PNI remains elusive. Drawing inspiration from the sea cucumber, we have integrated microneedles (MNs) and microchannel technology into nerve guidance conduits (NGCs) to develop bionic microneedle NGCs (MNGCs) that emulate the structure and piezoelectric function of sea cucumbers. Morphologically, MNGCs feature an outer surface with outward-pointing needle tips capable of applying electrical stimulation to denervated muscles. Simultaneously, the interior contains microchannels designed to guide the migration of Schwann cells (SCs). Physiologically, the incorporation of conductive reduced graphene oxide and piezoelectric zinc oxide nanoparticles into the polycaprolactone scaffold enhances conductivity and piezoelectric properties, facilitating SCs' migration, myelin regeneration, axon growth, and the restoration of neuromuscular function. These combined effects ultimately lead to the inhibition of muscle atrophy and the restoration of nerve function. Consequently, the concept of the synergistic effect of inhibiting muscle atrophy and promoting nerve regeneration has the capacity to transform the traditional approach to PNI repair and find broad applications in PNI repair.

Bioactivity-Based Molecular Networking-Guided Isolation of Epicolidines A-C from the Endophytic Fungus Epicoccum sp. 1-042.

Bioactivity-based molecular networking-guided fractionation enabled the isolation of three new polycyclic tetramic acids bearing cis-decalin, epicolidines A-C (1-3), along with one known compound, PF 1052 (4), from the endophytic fungus Epicoccum sp. 1-042 collected in Tibet, China. Their structures were assigned on the basis of extensive spectroscopic data, partial hydrolysis, advanced Marfey's method, quantum chemistry calculations, and X-ray diffraction analysis. Compounds 2-4 displayed promising activities against Gram-positive bacteria in vitro. Particularly, compound 4 displayed remarkable potential against vancomycin-resistant Enterococcus faecium (VRE) with an MIC value of 0.25 µg/mL, lower than the MIC (0.5 µg/mL) of the antibiotic combination quinupristin/dalfopristin (Q/D). In a further in vivo study, compound 4 increased the survival rate to 100% in the VRE-G. mellonella infection model at a concentration of 10 mg/kg.

Comparative analysis of GoPro and digital cameras in head and neck flap harvesting surgery video documentation: an innovative and efficient method for surgical education.

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.

Optical properties of monolithic zirconia fabricated with nanoparticle jetting.

STATEMENT OF PROBLEM: Excellent optical properties are essential for esthetic dental materials. However, the translucency and color masking ability of zirconia fabricated with nanoparticle jetting (NPJ), a type of printed zirconia, are unknown. PURPOSE: The purpose of this in vitro study was to evaluate the translucency and color masking ability of zirconia fabricated using NPJ. MATERIAL AND METHODS: A total of 90 specimens with thicknesses of 1.5, 1.0, and 0.5 mm were fabricated using high translucent milled zirconia (HT), low translucent milled zirconia (LT), and NPJ. CIELab values (L*, a*, and b*) of the specimens over 7 backgrounds, black, white, VitaB1, VitaA2, VitaA4, gold alloy (Au), and titanium (Ti), were obtained using a spectral radiometer. The relative translucency parameter (RTP) and color difference (∆E) of specimens over VitaB1, VitaA4, Au, and Ti were determined using VitaA2 as the control with the CIEDE2000 color difference equation. The normality of the data distribution was determined using the Shapiro-Wilk test. Differences among groups were analyzed using 2-way analysis of variance and the Student-Newman-Keuls (SNK) post hoc test (α=.05). The ∆E of specimens was analyzed according to perceptibility (∆E=0.8) and acceptability (∆E=1.8) thresholds using the 1 sample t test. The correlation between RTP and ∆E and RTP/∆E and thickness was examined using the Pearson correlation analysis. RESULTS: Statistically significant differences were observed in translucency and color masking ability among HT, LT, and NPJ (P<.05). The RTP value was the lowest for zirconia fabricated with NPJ (P<.001) and highest for HT (P<.001). Monolithic zirconia fabricated with NPJ had lower ∆E values than those of HT and LT for the same thickness and background (P<.05). A positive correlation was found in RTP and ∆E (P<.001). A negative correlation was observed in RTP and thickness (P<.001) and ∆E and thickness across a constant background (P<.001). CONCLUSIONS: Zirconia fabricated with NPJ was less translucent and had a greater color masking ability for discolored backgrounds than HT and LT.

Collapse of carbon nanotubes due to local high-pressure from van der Waals encapsulation.

Van der Waals (vdW) assembly of low-dimensional materials has proven the capability of creating structures with on-demand properties. It is predicted that the vdW encapsulation can induce a local high-pressure of a few GPa, which will strongly modify the structure and property of trapped materials. Here, we report on the structural collapse of carbon nanotubes (CNTs) induced by the vdW encapsulation. By simply covering CNTs with a hexagonal boron nitride flake, most of the CNTs (≈77%) convert from a tubular structure to a collapsed flat structure. Regardless of their original diameters, all the collapsed CNTs exhibit a uniform height of ≈0.7 nm, which is roughly the thickness of bilayer graphene. Such structural collapse is further confirmed by Raman spectroscopy, which shows a prominent broadening and blue shift in the Raman G-peak. The vdW encapsulation-induced collapse of CNTs is fully captured by molecular dynamics simulations of the local vdW pressure. Further near-field optical characterization reveals a metal-semiconductor transition in accompany with the CNT structural collapse. Our study provides not only a convenient approach to generate local high-pressure for fundamental research, but also a collapsed-CNT semiconductor for nanoelectronic applications.

Enhancing Image-Guided Radiation Therapy for Pancreatic Cancer: Utilizing Aligned Peak Response Beamforming in Flexible Array Transducers.

To develop ultrasound-guided radiotherapy, we proposed an assistant structure with embedded markers along with a novel alternative method, the Aligned Peak Response (APR) method, to alter the conventional delay-and-sum (DAS) beamformer for reconstructing ultrasound images obtained from a flexible array. We simulated imaging targets in Field-II using point target phantoms with point targets at different locations. In the experimental phantom ultrasound images, image RF data were acquired with a flexible transducer with in-house assistant structures embedded with needle targets for testing the accuracy of the APR method. The lateral full width at half maximum (FWHM) values of the objective point target (OPT) in ground truth ultrasound images, APR-delayed ultrasound images with a flat shape, and images acquired with curved transducer radii of 500 mm and 700 mm were 3.96 mm, 4.95 mm, 4.96 mm, and 4.95 mm. The corresponding axial FWHM values were 1.52 mm, 4.08 mm, 5.84 mm, and 5.92 mm, respectively. These results demonstrate that the proposed assistant structure and the APR method have the potential to construct accurate delay curves without external shape sensing, thereby enabling a flexible ultrasound array for tracking pancreatic tumor targets in real time for radiotherapy.

BAG3 promotes proliferation and migration of arterial smooth muscle cells by regulating STAT3 phosphorylation in diabetic vascular remodeling.

BACKGROUND: Diabetic vascular remodeling is the most important pathological basis of diabetic cardiovascular complications. The accumulation of advanced glycation end products (AGEs) caused by elevated blood glucose promotes the proliferation and migration of vascular smooth muscle cells (VSMCs), leading to arterial wall thickening and ultimately vascular remodeling. Therefore, the excessive proliferation and migration of VSMCs is considered as an important therapeutic target for vascular remodeling in diabetes mellitus. However, due to the lack of breakthrough in experiments, there is currently no effective treatment for the excessive proliferation and migration of VSMCs in diabetic patients. Bcl-2-associated athanogene 3 (BAG3) protein is a multifunctional protein highly expressed in skeletal muscle and myocardium. Previous research has confirmed that BAG3 can not only regulate cell survival and apoptosis, but also affect cell proliferation and migration. Since the excessive proliferation and migration of VSMCs is an important pathogenesis of vascular remodeling in diabetes, the role of BAG3 in the excessive proliferation and migration of VSMCs and its molecular mechanism deserve further investigation. METHODS: In this study, BAG3 gene was manipulated in smooth muscle to acquire SM22αCre; BAG3FL/FL mice and streptozotocin (STZ) was used to simulate diabetes. Expression of proteins and aortic thickness of mice were detected by immunofluorescence, ultrasound and hematoxylin-eosin (HE) staining. Using human aorta smooth muscle cell line (HASMC), cell viability was measured by CCK-8 and proliferation was measured by colony formation experiment. Migration was detected by transwell, scratch experiments and Phalloidin staining. Western Blot was used to detect protein expression and Co-Immunoprecipitation (Co-IP) was used to detect protein interaction. RESULTS: In diabetic vascular remodeling, AGEs could promote the interaction between BAG3 and signal transducer and activator of transcription 3 (STAT3), leading to the enhanced interaction between STAT3 and Janus kinase 2 (JAK2) and reduced interaction between STAT3 and extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in accumulated p-STAT3(705) and reduced p-STAT3(727). Subsequently, the expression of matrix metallopeptidase 2 (MMP2) is upregulated, thus promoting the migration of VSMCs. CONCLUSIONS: BAG3 upregulates the expression of MMP2 by increasing p-STAT3(705) and decreasing p-STAT3(727) levels, thereby promoting vascular remodeling in diabetes. This provides a new orientation for the prevention and treatment of diabetic vascular remodeling.

Family Environment Modulates Linkage of Transdiagnostic Psychiatric Phenotypes and Dissociable Brain Features in the Developing Brain.

BACKGROUND: Family environment has long been known for shaping brain function and psychiatric phenotypes, especially during childhood and adolescence. Accumulating neuroimaging evidence suggests that across different psychiatric disorders, common phenotypes may share common neural bases, indicating latent brain-behavior relationships beyond diagnostic categories. However, the influence of family environment on the brain-behavior relationship from a transdiagnostic perspective remains unknown. METHODS: We included a community-based sample of 699 participants (ages 5-22 years) and applied partial least squares regression analysis to determine latent brain-behavior relationships from whole-brain functional connectivity and comprehensive phenotypic measures. Comparisons were made between diagnostic and nondiagnostic groups to help interpret the latent brain-behavior relationships. A moderation model was introduced to examine the potential moderating role of family factors in the estimated brain-behavior associations. RESULTS: Four significant latent brain-behavior pairs were identified that reflected the relationship of dissociable brain network and general behavioral problems, cognitive and language skills, externalizing problems, and social dysfunction, respectively. The group comparisons exhibited interpretable variations across different diagnostic groups. A warm family environment was found to moderate the brain-behavior relationship of core symptoms in internalizing disorders. However, in neurodevelopmental disorders, family factors were not found to moderate the brain-behavior relationship of core symptoms, but they were found to affect the brain-behavior relationship in other domains. CONCLUSIONS: Our findings leveraged a transdiagnostic analysis to investigate the moderating effects of family factors on brain-behavior associations, emphasizing the different roles that family factors play during this developmental period across distinct diagnostic groups.