Interactions of genes with alcohol consumption affect insulin sensitivity and beta cell function.

AIMS/HYPOTHESIS: Alcohol consumption has complex effects on diabetes and metabolic disease, but there is widespread heterogeneity within populations and the specific reasons are unclear. Genetic factors may play a role and warrant exploration. The aim of this study was to elucidate genetic variants modulating the impact of alcohol consumption on insulin sensitivity and pancreatic beta cell function within populations presenting normal glucose tolerance (NGT). METHODS: We recruited 4194 volunteers in Nanjing, 854 in Jurong and an additional 5833 in Nanjing for Discovery cohorts 1 and 2 and a Validation cohort, respectively. We performed an OGTT on all participants, establishing a stringent NGT group, and then assessed insulin sensitivity and beta cell function. Alcohol consumption was categorised as abstinent, light-to-moderate (<210 g per week) or heavy (≥210 g per week). After excluding ineligible individuals, an exploratory genome-wide association study identified potential variants interacting with alcohol consumption in 1862 NGT individuals. These findings were validated in an additional cohort of 2169 NGT individuals. Cox proportional hazard regression was further employed to evaluate the effect of the interaction between the potential variants and alcohol consumption on the risk of type 2 diabetes within the UK Biobank cohort. RESULTS: A significant correlation was observed between drinking levels and insulin sensitivity, accompanied by a consequent inverse relationship with insulin resistance and beta cell insulin secretion after adjusting for confounding factors in NGT individuals. However, no significant associations were noted in the disposition indexes. The interaction of variant rs56221195 with alcohol intake exhibited a pronounced effect on the liver insulin resistance index (LIRI) in the discovery set, corroborated in the validation set (combined p=1.32 × 10-11). Alcohol consumption did not significantly affect LIRI in rs56221195 wild-type (TT) carriers, but a strong negative association emerged in heterozygous (TA) and homozygous (AA) individuals. The rs56221195 variant also significantly interacts with alcohol consumption, influencing the total insulin secretion index INSR120 (the ratio of the AUC of insulin to glucose from 0 to 120 min) (p=2.06 × 10-9) but not disposition index. In the UK Biobank, we found a significant interaction between rs56221195 and alcohol consumption, which was linked to the risk of type 2 diabetes (HR 0.897, p=0.008). CONCLUSIONS/INTERPRETATION: Our findings reveal the effects of the interaction of alcohol and rs56221195 on hepatic insulin sensitivity in NGT individuals. It is imperative to weigh potential benefits and detriments thoughtfully when considering alcohol consumption across diverse genetic backgrounds.

The relationship of neurocognitive and social cognitive performance to social competence and appropriateness on a performance-based social skills assessment in individuals with psychosis and unaffected controls.

Social deficits are common in psychosis. The Social Skills Performance Assessment (SSPA) is a performance-based measure used to approximate an individual's social skills. Those with psychosis perform worse than do unaffected controls. Prior work has examined two social skills domains derived from the SSPA: social competence and social appropriateness. Social competence and appropriateness are associated with neurocognition and functioning outcomes. However, no study to date has examined the relationship of social cognition to social competence and appropriateness. We aimed to examine the relationships among different aspects of social cognition and performance-based social functioning and hypothesized that social cognitive performance would be related to social competence and appropriateness. We also hypothesized that after controlling for neurocognition, social cognition would account for unique variance in social competence and appropriateness in separate regression models. Forty-one participants who had experienced psychosis and 42 unaffected controls completed a comprehensive battery of neurocognitive, social cognitive, and social functioning measures. Social competence was associated with neurocognition and some aspects of social cognition, while social appropriateness was only marginally associated with neurocognition. Regression models revealed that social cognition did not account for additional and unique variance in social competence or appropriateness, after adjusting for demographic covariates and neurocognition. Findings suggest that aspects of social functioning performance are differentially related to neurocognitive and social cognitive skills. Social skill interventions may be most effective when targeting both neurocognitive and social cognitive skills in treatment.

Performance of antisaccades in patients with cerebral small vessel disease accompanied by white matter hyperintensities.

OBJECTIVES: The antisaccades (AS) task is considered a reliable indicator of inhibitory control of eye movements in humans. Achieving good AS performance requires efficient cognitive processes that are sensitive to changes in brain structure. White matter hyperintensities (WMH) can cause subcortical-cortical dysconnectivity, affecting diverse cognitive domains. Thus, the AS task was investigated in patients with WMH in cerebral small vessel disease (CSVD). METHODS: In this retrospective study, 75 participants with WMH, determined by neuroimaging standards for CSVD research, were admitted to the Department of Neurology of Beijing Luhe Hospital, Capital Medical University from January 2021 to December 2022. All subjects underwent the AS task, Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and 3.0T brain MRI. Additionally, 61 healthy subjects were recruited to characterize WMH profiles. RESULTS: Compared to the control group, patients with WMH had a significantly increased AS error rate (49.81%, p = 0.001) and lower gain (76.00%, p = 0.042). The AS error rate was significantly higher in patients with WMH in the frontal lobe than in those without WMH (p = 0.004). After adjusting for confounders (age), a positive correlation was found between the AS error rate and MoCA scores for patients with WMH (coefficient = 0.262, p = 0.024). CONCLUSIONS: Patients with WMH due to CSVD exhibited abnormal AS performances, particularly in the frontal lobe. The eye movement paradigms, the new diagnostic forms in neurology, can be utilized to investigate the distributed cortical and subcortical systems involved in cognitive control processes, offering simple, well-tolerated and highly sensitive advantages over traditional measures.

Activation of TAS2R4 signaling attenuates podocyte injury induced by high glucose.

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C ß2 (PLCß2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCß2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gßγ inhibitor Gallein, or a PLCß2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease.

Post-stroke dizziness, depression and anxiety.

OBJECTIVE: Vestibular and psychiatric disorders are very closely related. Previous research shows that the discomfort and dysfunction caused by dizziness in patients can affect psychological processes, leading to anxiety and depression, and the irritation of anxiety and depression can aggravate the discomfort of dizziness. But the causal relationship between dizziness in the recovery period of stroke and Post-stroke depression (PSD) / Post-stroke anxiety (PSA) is not clear. Identifying the causal relationship between them can enable us to conduct more targeted treatments. METHODS: We review the epidemiology and relationship of dizziness, anxiety, and depression, along with the related neuroanatomical basis. We also review the pathophysiology of dizziness after stroke, vestibular function of patients experiencing dizziness, and the causes and mechanisms of PSD and PSA. We attempt to explore the possible relationship between post-stroke dizziness and PSD and PSA. CONCLUSION: The treatment approach for post-stroke dizziness depends on its underlying cause. If the dizziness is a result of PSD and PSA, addressing these psychological factors may alleviate the dizziness. This can be achieved through targeted treatments for PSD and PSA, such as psychotherapy, antidepressants, or anxiolytics, which could indirectly improve dizziness symptoms. Conversely, if PSA and PSD are secondary to vestibular dysfunction caused by stroke, a thorough vestibular function assessment is crucial. Identifying the extent of vestibular impairment allows for tailored interventions. These could include vestibular rehabilitation therapy and medication aimed at vestibular restoration. By improving vestibular function, secondary symptoms like anxiety and depression may also be mitigated.

Overlooked uneven progress across sustainable development goals at the global scale: Challenges and opportunities.

Differences in progress across sustainable development goals (SDGs) are widespread globally; meanwhile, the rising call for prioritizing specific SDGs may exacerbate such gaps. Nevertheless, how these progress differences would influence global sustainable development has been long neglected. Here, we present the first quantitative assessment of SDGs' progress differences globally by adopting the SDGs progress evenness index. Our results highlight that the uneven progress across SDGs has been a hindrance to sustainable development because (1) it is strongly associated with many public health risks (e.g., air pollution), social inequalities (e.g., gender inequality, modern slavery, wealth gap), and a reduction in life expectancy; (2) it is also associated with deforestation and habitat loss in terrestrial and marine ecosystems, increasing the challenges related to biodiversity conservation; (3) most countries with low average SDGs performance show lower progress evenness, which further hinders their fulfillment of SDGs; and (4) many countries with high average SDGs performance also showcase stagnation or even retrogression in progress evenness, which is partly ascribed to the antagonism between climate actions and other goals. These findings highlight that while setting SDGs priorities may be more realistic under the constraints of multiple global stressors, caution must be exercised to avoid new problems from intensifying uneven progress across goals. Moreover, our study reveals that the urgent needs regarding SDGs of different regions seem complementary, emphasizing that regional collaborations (e.g., demand-oriented carbon trading between SDGs poorly performed and well-performed countries) may promote sustainable development achievements at the global scale.

Lateral Prefrontal Stimulation of Active Cortex With Theta Burst Transcranial Magnetic Stimulation Affects Subsequent Engagement of the Frontoparietal Network.

BACKGROUND: A critical unanswered question about therapeutic transcranial magnetic stimulation is what patients should do during treatment to optimize its effectiveness. Here, we address this lack of knowledge in healthy participants, testing the hypotheses that stimulating the left dorsolateral prefrontal cortex (dlPFC) while participants perform a working memory task will provide stronger effects on subsequent activation, perfusion, connectivity, and performance than stimulating resting dlPFC. METHODS: After a baseline functional magnetic resonance imaging session to localize dlPFC activation and the associated frontoparietal network (FPN) engaged by an n-back task, healthy participants (N = 40, 67.5% female) underwent 3 counterbalanced sessions, separated by several weeks, during which they received intermittent theta burst stimulation (iTBS) followed by magnetic resonance imaging scans as follows: 1) iTBS to the dlPFC while resting passively (passive), 2) iTBS to the dlPFC while performing the n-back task (active), and 3) iTBS to a vertex site, while not engaged in the n-back task and resting passively (control). RESULTS: We found no difference in n-back performance between the 3 conditions. However, FPN activation was reduced while performing the n-back task in the active condition relative to the passive and control conditions. There was no differential activity in the FPN on comparing passive with control conditions, i.e., there was no effect of the site of stimulation. We found no effects of state or site of stimulation on perfusion or connectivity with the dlPFC. CONCLUSIONS: In this study, the state of the brain while receiving iTBS affected FPN activation, possibly reflecting greater efficiency of FPN network activation when participants were stimulated while engaging the FPN.

Decoding the Pathway-Dependent Self-Assembly of Polymer-Grafted Nanoparticles by Ligand Crystallization.

Functional metamaterials can be constructed by assembling nanoparticles (NPs) into well-ordered structures, which show fascinating properties at different length scales. Using polymer-grafted NPs (PGNPs) as a building block, flexible composite metamaterials can be obtained, of which the structure is significantly affected by the property of polymer ligands. Here, it is demonstrated that the crystallization of polymer ligands determines the assembly behavior of NPs and reveal a pathway-dependent self-assembly of PGNPs into different metastructures in solution. By changing the crystallization degree of polymer ligands, the arrangement structure of NPs can be tailored. When the polymer ligands highly crystallize, the PGNPs assemble into diamond-shaped platelets, in which the NPs arrange disorderedly. When the polymer ligands lowly crystallize, the PGNPs assemble into highly ordered 3D superlattices, in which the NPs pack into a body-centered-cubic structure. The structure transformation of PGNP assemblies can be achieved by thermal annealing to regulate the crystallization of polymer ligands. Interestingly, the diamond-shaped platelets remain "living" for seeded epitaxial growth of newly added crystalline species. This work demonstrates the effects of ligand crystallization on the crystallization of NP, providing new insights into the structure regulation of metamaterials.

Vestibular function is associated with immune inflammatory response.

Association between vestibular function and immune inflammatory response has garnered increasing interest. Immune responses can lead to anatomical or functional alterations of the vestibular system, and inflammatory reactions may impair hearing and balance. Vestibular disorders comprise a variety of conditions, such as vestibular neuritis, benign paroxysmal positional vertigo, Meniere's disease, vestibular migraine, posterior circulation ischemia, and bilateral vestibular disease. Moreover, some patients with autoimmune diseases develop vestibulocochlear symptom. This paper offers an overview of prevalent vestibular diseases and discusses associations between vestibular dysfunction and immune diseases.

WD-YOLO: A More Accurate YOLO for Defect Detection in Weld X-ray Images.

X-ray images are an important industrial non-destructive testing method. However, the contrast of some weld seam images is low, and the shapes and sizes of defects vary greatly, which makes it very difficult to detect defects in weld seams. In this paper, we propose a gray value curve enhancement (GCE) module and a model specifically designed for weld defect detection, namely WD-YOLO. The GCE module can improve image contrast to make detection easier. WD-YOLO adopts feature pyramid and path aggregation designs. In particular, we propose the NeXt backbone for extraction and fusion of image features. In the YOLO head, we added a dual attention mechanism to enable the model to better distinguish between foreground and background areas. Experimental results show that our model achieves a satisfactory balance between performance and accuracy. Our model achieved 92.6% mAP@0.5 with 98 frames per second.

Structural connectivity of an interoception network in schizophrenia.

Interoception refers to the processing, integration, and interpretation of bodily signals by the brain. Interoception is key to not only basic survival, but also motivational and affective functioning. There is emerging evidence suggesting altered interoception in schizophrenia, but few studies have explored potential neural underpinnings. The current study aims to investigate the anatomical connectivity of a previously identified interoception network in individuals with schizophrenia, and the relationship between network structural connectivity and both emotional functioning and clinical symptoms. Thirty-five participants with schizophrenia (SZ) and 36 healthy control participants (HC) underwent diffusion tensor imaging (DTI) and performed tasks measuring emotional functioning. Probabilistic tractography was used to identify white matter tracts connecting key hubs in an interoception network. Microstructural integrity of these tracts was compared across groups and correlated with measures of emotional functioning and symptom severity. Compared with HC, SZ exhibited altered structural connectivity in the interoception network. In HC, the structural connectivity of the network was significantly correlated with emotion recognition, supporting a link between the interoception network and emotional functioning. However, this correlation was much weaker in SZ. These findings suggest that altered interoception may have implications for illness mechanisms of schizophrenia, especially in relation to emotional deficits.

Large-Area Arrays of Polymer-Tethered Gold Nanorods with Controllable Orientation and Their Application in Nano-Floating-Gate Memory Devices.

In this work, it is reported that large-area (centimeter-scale) arrays of non-close-packed polystyrene-tethered gold nanorod (AuNR@PS) can be prepared through a liquid-liquid interfacial assembly method. Most importantly, the orientation of AuNRs in the arrays can be controlled by changing the intensity and direction of electric field applied in the solvent annealing process. The interparticle distance of AuNR can be tuned by varying the length of polymer ligands. Moreover, the AuNR@PS with short PS ligand are favorited to form orientated arrays with the assistance of electric field, while long PS ligands make the orientation of AuNRs difficult. The orientated AuNR@PS arrays are employed as the nano-floating gate of field-effect transistor memory device. Tunable charge trapping and retention characteristics in the device can be realized by electrical pulse with visible light illumination. The memory device with orientated AuNR@PS array required less illumination time (1 s) at the same onset voltage in programming operation, compared to the control device with disordered AuNR@PS array (illumination time: 3 s). Moreover, the orientated AuNR@PS array-based memory device can maintain the stored data for more than 9000 s, and exhibits stable endurance characteristic without significant degradation in 50 programming/reading/erasing/reading cycles.

Abnormally Enhanced Midfrontal Theta Activity During Response Monitoring in Youths With Obsessive-Compulsive Disorder.

BACKGROUND: Response monitoring, as reflected in electroencephalogram recordings after commission of errors, has been consistently shown to be abnormally enhanced in individuals with obsessive-compulsive disorder (OCD). This has traditionally been quantified as error-related negativity (ERN) and may reflect abnormal neurophysiological mechanisms underlying OCD. However, the ERN reflects the increase in phase-locked activities, particularly in the theta-band (4-8 Hz), and does not reflect non-phase-locked activities. To more broadly investigate midfrontal theta activity in a brain region that is essential for complex cognition, this study investigated theta abnormalities during response monitoring in participants with OCD to acheive a better understanding of the mechanism underlying the ERN. METHODS: Electroencephalogram data were recorded from 99 participants with pediatric OCD and 99 sex- and age-matched healthy control participants while they completed the arrow flanker task. Effects of group (OCD, healthy control) and response type (error, correct) on postresponse theta total power and intertrial phase coherence (ITPC) were examined using mixed analysis of covariance and Bayesian analyses controlling for sex and accuracy. RESULTS: Theta total power was larger on error than on correct trials and larger in OCD than healthy control participants, but there was no effect of response type between groups. Theta ITPC was larger on error than correct trials, but there was no group difference or response type difference between the groups. Correlations of theta total power and ITPC with clinical measures were overall small. CONCLUSIONS: Abnormally enhanced midfrontal theta total power, but not ITPC, may reflect ineffective heightened response monitoring or compensatory activity in pediatric OCD.

OOCDB: A Comprehensive, Systematic, and Real-time Organs-on-a-chip Database.

Organs-on-a-chip is a microfluidic microphysiological system that uses microfluidic technology to analyze the structure and function of living human cells at the tissue and organ levels in vitro. Organs-on-a-chip technology, as opposed to traditional two-dimensional cell culture and animal models, can more closely simulate pathologic and toxicologic interactions between different organs or tissues and reflect the collaborative response of multiple organs to drugs. Despite the fact that many organs-on-a-chip-related data have been published, none of the current databases have all of the following functions: searching, downloading, as well as analyzing data and results from the literature on organs-on-a-chip. Therefore, we created an organs-on-a-chip database (OOCDB) as a platform to integrate information about organs-on-a-chip from various sources, including literature, patents, raw data from microarray and transcriptome sequencing, several open-access datasets of organs-on-a-chip and organoids, and data generated in our laboratory. OOCDB contains dozens of sub-databases and analysis tools, and each sub-database contains various data associated with organs-on-a-chip, with the goal of providing researchers with a comprehensive, systematic, and convenient search engine. Furthermore, it offers a variety of other functions, such as mathematical modeling, three-dimensional modeling, and citation mapping, to meet the needs of researchers and promote the development of organs-on-a-chip. The OOCDB is available at http://www.organchip.cn.

Excitatory Projections from the Prefrontal Cortex to Nucleus Accumbens Core D1-MSNs and κ Opioid Receptor Modulate Itch-Related Scratching Behaviors.

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of κ opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.SIGNIFICANCE STATEMENT Itch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the nucleus accumbens (NAc) core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of κ opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.

Electric, magnetic, and shear field-directed assembly of inorganic nanoparticles.

Ordered assemblies of inorganic nanoparticles (NPs) have shown tremendous potential for wide applications due to their unique collective properties, which differ from those of individual NPs. Various assembly methods, such as external field-directed assembly, interfacial assembly, template assembly, biomolecular recognition-mediated assembly, confined assembly, and others, have been employed to generate ordered inorganic NP assemblies with hierarchical structures. Among them, the external field-directed assembly method is particularly fascinating, as it can remotely assemble NPs into well-ordered superstructures. Moreover, external fields (e.g., electric, magnetic, and shear fields) can introduce a local and/or global field intensity gradient, resulting in an additional force on NPs to drive their rotation and/or translation. Therefore, the external field-directed assembly of NPs becomes a robust method to fabricate well-defined functional materials with the desired optical, electronic, and magnetic properties, which have various applications in catalysis, sensing, disease diagnosis, energy conversion/storage, photonics, nano-floating-gate memory, and others. In this review, the effects of an electric field, magnetic field, and shear field on the organization of inorganic NPs are highlighted. The methods for controlling the well-ordered organization of inorganic NPs at different scales and their advantages are reviewed. Finally, future challenges and perspectives in this field are discussed.

Histone deacetylase 5-induced deficiency of signal transducer and activator of transcription-3 acetylation contributes to spinal astrocytes degeneration in painful diabetic neuropathy.

Diabetes patients with painful diabetic neuropathy (PDN) show severe spinal atrophy, suggesting pathological changes of the spinal cord contributes to central sensitization. However, the cellular changes and underlying molecular mechanisms within the diabetic spinal cord are less clear. By using a rat model of type 1 diabetes (T1D), we noted an extensive and irreversible spinal astrocyte degeneration at an early stage of T1D, which is highly associated with the chronification of PDN. Molecularly, acetylation of astrocytic signal transducer and activator of transcription-3 (STAT3) that is essential for maintaining the homeostatic astrocytes population was significantly impaired in the T1D model, resulting in a dramatic loss of spinal astrocytes and consequently promoting pain hypersensitivity. Mechanistically, class IIa histone deacetylase, HDAC5 were aberrantly activated in spinal astrocytes of diabetic rats, which promoted STAT3 deacetylation by direct protein-protein interactions, leading to the PDN phenotypes. Restoration of STAT3 signaling or inhibition of HDAC5 rescued astrocyte deficiency and attenuated PDN in the T1D model. Our work identifies the inhibitory axis of HDAC5-STAT3 induced astrocyte deficiency as a key mechanism underlying the pathogenesis of the diabetic spinal cord that paves the way for potential therapy development for PDN.

In Situ Self-Assembly of Nanoscale Particles into Macroscale Ordered Monolayers with Enhanced Memory Performance.

In situ fabrication of macroscale ordered monolayers of nanoparticles (NPs) on targeted substrates is highly desirable for precision electronic and optical devices, while it remains a great challenge. In this study, a solution is provided to address this challenge by developing a colloidal ink formulation and employing the direct-ink-writing (DIW) technique, where on-demand delivery of ink at a targeted location and directional evaporation with controllable rate are leveraged to precisely guide the deposition of polystyrene-grafted gold NPs (Au@PS NPs) into a macroscale monolayer with an ordered Au NP array embedded in a PS thin film. A 2D steady-state diffusion-controlled evaporation model, which explains the parameter dependence of the experimental results and gives semiquantitative agreement with the experimental evaporation kinetics is proposed. The ordered monolayer is used as both nanocrystal floating gates and the tunneling layer for nonvolatile memory devices. It shows significantly enhanced performance compared with a disordered NP film prepared by spin coating. This approach allows for fine control of NP self-assembly to print macroscaleordered monolayers directly onto substrates, which has great promise for application in broad fields, including microelectronic and photoelectronic devices, sensors, and functional coatings.

Preliminary study on the advantages of hysteroscopic myomectomy with cold knife. / å®«è ”é•œä¸‹å†·åˆ€åˆ‡é™¤é»è†œä¸‹è‚Œç˜¤ä¼˜åŠ¿çš„åˆæ­¥æŽ¢è®¨.

OBJECTIVES: At present, hysteroscopic submucosal fibroids resection is mostly performed by hysteroscopic electric resection (hereinafter referred to as electric knife). During the operation, the electrothermal effect could not only damage the endometrial tissues covered by the surface of the fibroid, but also easily damage the endometrial tissues around the fibroid, which is very unfavorable for patients with fertility requirements. In addition, for some special fibroids (located at horn and fundus) or Type II and multiple submucosal fibroids, the traditional electric resection is still very difficult. With the opening of the second-child policy and the urgent desire of patients for fertility, more and more attention is paid to the concept of fertility protection in China. Therefore, hysteroscopic cold knife technology (hereinafter referred to as cold knife) has gradually entered the vision. The cold knife has the advantages of simple operation, such as little trauma and quick postoperative recovery. In this study, the advantages of cold knife in the surgical resection of submucosal fibroids are discussed by comparing the safety and effectiveness between the hysteroscopic cold knife resection (hereinafter referred to as cold knife) and the electric knife resection in the submucosal fibroids. METHODS: The clinical data of 112 patients with submucosal fibroids diagnosed and treated by hysteroscopic surgery at the Third Xiangya Hospital of Central South University from January 2017 to October 2021 were retrospectively analyzed, including preoperative general information (such as age, gravidity, abortion times, the size, location, type and number of submucosal fibroids, preoperative hemoglobin value) and intraoperative conditions [such as intraoperative bleeding, the operation time, residual rates and intraoperative complications (massive bleeding, perforation, water poisoning)]. The patients were divided into a cold knife group and an electric knife group, and there were 40 cases in the cold knife group and 72 cases in the electric knife group. The postoperative complications and the pregnancy outcomes in the 2 groups were followed up by telephone, the follow-up data included postoperative recurrence rate, pregnancy rate, pregnancy mode, and pregnancy outcome. RESULTS: Compared with the electric knife group, the cold knife group had more submucous myomas located in the horn or fundus of the uterus (9.7% vs 25.0%), and more Type II myomas or combined with Type II myomas (26.4% vs 70.0%). However, there were no significant difference in intraoperative bleeding, the operation time, intraoperative complications and the residual rates between the 2 groups (all P>0.05). A total of 98 patients were followed up, including 32 patients in the cold knife group and 66 patients in the electric knife group. Compared with the electric knife group, there were lower postoperative complications in the cold knife group (12.5% vs 37.9%) (P<0.05). Among the 7 patients with multiple submucosal fibroids (the number of fibroids ≥5), there were 4 patients in the electric knife group and 3 patients in the cold knife group. In the electric knife group, the postoperative menstrual volume in the 4 patients was significantly reduced and 3 patients had postoperative fertility requirements, which were all diagnosed as intrauterine adhesion by hysteroscopy and performed further surgery. Later, 2 patients had successful pregnancy, 1 had miscarriage, and 1 had full-term spontaneous labor. However, the menstrual volume of the 3 patients in the cold knife group was not significantly reduced compared with normal menstrual volume, and 2 of them had fertility requirements, and they had natural pregnancy and full term vaginal delivery. There were no significant differences in postoperative recurrence rate, pregnancy rate, pregnancy mode and pregnancy outcome between the 2 groups (all P>0.05). CONCLUSIONS: Both the electric knife and cold knife resection are safe and effective methods for the treatment of submucosal fibroids. Compared with electric knife resection, the cold knife resection has fewer postoperative complications and perhaps more advantages in endometrial protection, especially for the patients with fertility requirements, submucosal fibroids located at the fundus or horn of the uterus, Type II submucosal fibroids, and multiple submucosal fibroids.

A model established for predicting natural pregnancy possibility based on the imaging characteristics of 4-dimensional hysterosalpingo-contrast sonography. / åŸºäºŽå››ç»´è¶ å£°å­å®«è¾“åµç®¡é€ å½±çš„å½±åƒå­¦ç‰¹å¾å»ºç«‹è‡ªç„¶å¦Šå¨ é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: The incidence of infertility is increasing, more than 30% of them having related abnormal tubal patency. Four-dimensional (4D) hysterosalpingo-contrast sonography (HyCoSy) overcomes the shortcomings of 3D HyCoSy in the diagnosis of tubal patency, showing high specificity and accuracy. In addition, 4D HyCoSy discards iodine allergy and X-ray radiation and possesses easy-operating, contributing to good acceptance in clinical practice. However, there is no research to explore the imaging standards related to the possibility of natural pregnancy after 4D HyCoSy. If a predictive model of postoperative natural pregnancy was established using the analysis of clinical data combined with imaging characteristics of 4D HyCoSy of patients with tubal factor infertility, clinical decision-making can be wisely guided in the future. This study aims to establish a predictive model of natural pregnancy after 4D HyCoSy based on clinical data and imaging characteristics of patients with tubal factor in fertility. METHODS: A retrospective study was conducted for patients who were diagnosed with tubal factor infertility in Hunan Guangxiu Hospital from February 2017 to May 2018. The patients ought to possess complete 4D HyCoSy imaging data and at least one-side-unobstructed fallopian tube. General clinical data and imaging data were collected. Pregnancy outcome was followed up till 3 months after 4D HyCoSy. According to pregnancy outcome, patients were divided into a pregnancy group and a non-pregnancy group. Binary logistic regression was used to analyze the correlation between various variables and natural pregnancy after 4D HyCoSy. The variables with significant difference (P<0.05) in single-factor logistic regression were included in the natural pregnancy probability prediction model. The classification accuracy was further verified with 10-fold cross-validation. RESULTS: A total of 1 085 patients with clinically suspected tubal factor infertility who met the requirements and followed the doctors' prescription were collected. Clinical characteristics (age and duration of infertility) and 4D HyCoSy imaging characteristics (thickness of endometrium from the 3rd to the 7th day after the end of menstruation, visualization of the left fallopian tube, the diffusion of contrast agent around the left ovary, and the diffusion of contrast agent around the right ovary) were independent predictors for natural pregnancy 3 months after 4D HyCoSy. A natural pregnancy probability prediction model was established with the area under the curve (AUC) verified by the 10-fold cross-validation all greater than 0.75, and the best AUC was 0.868. The Q value obtained by the prediction model was the probability of natural pregnancy, and the cutoff value was 0.5. When the Q value was greater than 0.5, it was recommended to attempt natural pregnancy for 3 months, and when the Q value was less than 0.5, in vitro fertilization was adviced. CONCLUSIONS: A predictive model for the evaluating probability of natural pregnancy in women with tubal factor infertility after 4D HyCoSy is successfully established based on the analysis for clinical data and imaging characteristics. This model shows a great potential in assisting clinical decision making.