Coronin 2B Regulates Neuronal Migration via Rac1-Dependent Multipolar-Bipolar Transition.

In the developing cortex, excitatory neurons migrate along the radial fibers to their final destinations and build up synaptic connection with each other to form functional circuitry. The shaping of neuronal morphologies by actin cytoskeleton dynamics is crucial for neuronal migration. However, it is largely unknown how the distribution and assembly of the F-actin cytoskeleton are coordinated. In the present study, we found that an actin regulatory protein, coronin 2B, is indispensable for the transition from a multipolar to bipolar morphology during neuronal migration in ICR mice of either sex. Loss of coronin 2B led to heterotopic accumulation of migrating neurons in the intermediate zone along with reduced dendritic complexity and aberrant neuronal activity in the cortical plate. This was accompanied by increased seizure susceptibility, suggesting the malfunction of cortical development in coronin 2B-deficient brains. Coronin 2B knockdown disrupted the distribution of the F-actin cytoskeleton at the leading processes, while the migration defect in coronin 2B-deficient neurons was partially rescued by overexpression of Rac1 and its downstream actin-severing protein, cofilin. Our results collectively reveal the physiological function of coronin 2B during neuronal migration whereby it maintains the proper distribution of activated Rac1 and the F-actin cytoskeleton.SIGNIFICANCE STATEMENT Deficits in neuronal migration during cortical development result in various neurodevelopmental disorders (e.g., focal cortical dysplasia, periventricular heterotopia, epilepsy, etc.). Most signaling pathways that control neuronal migration process converge to regulate actin cytoskeleton dynamics. Therefore, it is important to understand how actin dynamics is coordinated in the critical processes of neuronal migration. Herein, we report that coronin 2B is a key protein that regulates neuronal migration through its ability to control the distribution of the actin cytoskeleton and its regulatory signaling protein Rac1 during the multipolar-bipolar transition in the intermediate zone, providing insights into the molecular machinery that drives the migration process of newborn neurons.

Astrocyte-specific inhibition of sigma-1 receptor leads to depressive-like behaviors in mice via activation of NF-κB-induced neuroinflammation.

Major depressive disorder (MDD) is a global health burden characterized by persistent low mood, deprivation of pleasure, recurrent thoughts of death, and physical and cognitive deficits. The current understanding of the pathophysiology of MDD is lacking, resulting in few rapid and effective antidepressant therapies. Recent studies have pointed to the sigma-1 (σ-1) receptor as a potential rapid antidepressant target; σ-1 agonists have shown promise in a variety of preclinical depression models. Hypidone hydrochloride (YL-0919), an independently developed antidepressant by our institute with faster onset of action and low rate of side effects, has recently emerged as a highly selective σ-1 receptor agonist; however, its underlying astrocyte-specific mechanism is unknown. In this study, we investigated the effect of YL-0919 treatment on gene expression in the prefrontal cortex of depressive-like mice by single-cell RNA sequencing. Furthermore, we knocked down σ-1 receptors on astrocytes in the medial prefrontal cortex of mice to explore the effects of YL-0919 on depressive-like behavior and neuroinflammation in mice. Our results demonstrated that astrocyte-specific knockdown of σ-1 receptor resulted in depressive-like behavior in mice, which was reversed by YL-0919 administration. In addition, astrocytic σ-1 receptor deficiency led to activation of the NF-κB inflammatory pathway, and crosstalk between reactive astrocytes and activated microglia amplified neuroinflammation, exacerbating stress-induced neuronal apoptosis. Furthermore, the depressive-like behavior induced by astrocyte-specific knockdown of the σ-1 receptor was improved by a selective NF-κB inhibitor, JSH-23, in mice. Our study not only reaffirms the σ-1 receptor as a key target of the faster antidepressant effect of YL-0919, but also contributes to the development of astrocytic σ-1 receptor-based novel drugs.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Polo-like kinase 1 promotes pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development. METHODS: Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH. RESULTS: Hypoxia stimulated PLK1 expression through induction of HIF1α and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice. CONCLUSIONS: Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

A novel effect of PDLIM5 in α7 nicotinic acetylcholine receptor upregulation and surface expression.

Nicotinic acetylcholine receptors (nAChRs) are widespread throughout the central nervous system. Signaling through nAChRs contributes to numerous higher-order functions, including memory and cognition, as well as abnormalities such as nicotine addiction and neurodegenerative disorders. Although recent studies indicate that the PDZ-containing proteins comprising PSD-95 family co-localize with nicotinic acetylcholine receptors and mediate downstream signaling in the neurons, the mechanisms by which α7nAChRs are regulated remain unclear. Here, we show that the PDZ-LIM domain family protein PDLIM5 binds to α7nAChRs and plays a role in nicotine-induced α7nAChRs upregulation and surface expression. We find that chronic exposure to 1 µM nicotine upregulated α7, ß2-contained nAChRs and PDLIM5 in cultured hippocampal neurons, and the upregulation of α7nAChRs and PDLIM5 is increased more on the cell membrane than the cytoplasm. Interestingly, in primary hippocampal neurons, α7nAChRs and ß2nAChRs display distinct patterns of expression, with α7nAChRs colocalized more with PDLIM5. Furthermore, PDLIM5 interacts with α7nAChRs, but not ß2nAChRs in native brain neurons. Knocking down of PDLIM5 in SH-SY5Y abolishes nicotine-induced upregulation of α7nAChRs. In primary hippocampal neurons, using shRNA against PDLIM5 decreased both surface clustering of α7nAChRs and α7nAChRs-mediated currents. Proteomics analysis and isothermal titration calorimetry (ITC) results show that PDLIM5 interacts with α7nAChRs through the PDZ domain, and the interaction between PDLIM5 and α7nAChRs can be promoted by nicotine. Collectively, our data suggest a novel cellular role of PDLIM5 in the regulation of α7nAChRs, which may be relevant to plastic changes in the nervous system.

Effects of adverse childhood health experiences on cognitive function in Chinese middle-aged and older adults: mediating role of depression.

BACKGROUND: Adverse childhood experiences are critical factors in depression and cognitive decrease, but the effect of adverse childhood health experiences (ACHEs) on cognitive function and the role of depression have not been fully studied. METHODS: Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2018. This study used indicators of situational memory ability and mental status to measure cognitive capacity. Besides analyzing the different types of ACHEs, scores for ACHEs were calculated to represent the severity of ACHEs. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depression. The analysis of this study employed two different analytical strategies in order to examine the mediated effects of depression. We used Sobel's test and Baron and Kenny's causal step approach, which utilized a generalized least squares regression model. Furthermore, a logistic regression model was used to evaluate the robustness of the Karlson-Holm-Breen (KHB) approach. RESULTS: In this study, 6301 individuals who met the requirements of the study were included. We found that being confined to bed (ACHE3) (ß=-0.3846, p = 0.022) in childhood had a negative impact on cognitive function. Similarly, ACHEs had a negative effect on cognitive function (ß=-0.0819, p = 0.090). And after the depression had been introduced into the model, the regression coefficient of ACHEs on cognitive function was no longer significant (ß=-0.0170, p = 0.727). The Sobel test showed that for ACHE3, the mediated proportion of the total effect of depression was 36.92%. While for ACHEs, the proportion of the mediated effect of depression was 70.11%. Finally, a robustness test of the mediating effect using the KHB method revealed that the mediating effect still existed. Further, based on different gender, age, and educational levels, the heterogeneity test indicated that the relationship between ACHEs and cognitive function and mediating effects of the depression were different as well as passing the robustness test of the interaction. CONCLUSION: The decline in cognition had been shown to be correlated with ACHEs and depression mediated this relationship. Positive interventions might help to improve cognitive performance in individuals suffering from ACHEs and depression.

The correlation analysis of WeChat usage and depression among the middle-aged and elderly in China: the mediating role of social participation.

BACKGROUND: We aimed to explore the association between WeChat usage and depression in the Chinese middle-aged and elderly and the role of social participation. METHODS: Data were obtained from China Health and Retirement Longitudinal Study (CHARLS) of 2018. The dependent variable was depressive symptoms, measured with the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10). We used the propensity score matching (PSM) to match the WeChat users with the non-WeChat users. Correlations between WeChat usage and depressive symptoms were verified by using logistic regression and linear regression, and the mediating role of social participation was verified by using stepwise regression and KHB method. RESULTS: Four thousand five hundred forty-five samples were ultimately matched for analysis in this study. After including all control variables, results of logistic regression showed that WeChat usage was significantly associated with a lower prevalence of depression (aOR:0.701,95% CI: 0.605-0.812). And the results of linear regression showed that WeChat usage was associated with lower levels of depression which was significant (p < 0.001). The results of the stepwise regression and the KHB method showed a mediating role of social participation in WeChat usage and depressive symptoms. Among the four types of social participation, the mediating effect of recreational activities was significant, while the mediating effects of voluntary activities, cultural activities, and other activities were not significant. Meanwhile, the effect of WeChat usage on depression and the mediating effect of social participation were heterogeneous because of differences in age and gender. CONCLUSION: Social participation partly mediated the effect between WeChat usage and depression in middle-aged and older adults. Among the four types of social participation, only recreational activities had a mediating effect. Encouraging more active social participation and other types of social activities should be considered to improve the mental health of the middle-aged and older adults in China through social media usage.

White-Sutton syndrome and congenital heart disease: case report and literature review.

BACKGROUND: White-Sutton syndrome is an autosomal dominant neurodevelopmental disorder caused by heterozygous mutation in POGZ (Pogo Transposable Element Derived with ZNF Domain). This syndrome is characterized by delayed psychomotor development apparent in infancy and abnormal facial features. To date, 80 cases have been reported in the literature; however, the phenotypic characterizations remain incomplete. CASE PRESENTATION: We herein describe a 2-year-old girl harboring a novel frameshift de novo POGZ variant: c.2746del (p.Thr916ProfsTer12). This patient presented with multisystem abnormalities affecting the digestive tract and neurological functioning, as well as congenital heart disease, which involved an atrial septal defect (18 × 23 × 22 mm) with pulmonary arterial hypertension (42 mmHg). The relationship between congenital heart disease and White-Sutton syndrome as described in both the GeneReview and OMIM databases (#616,364) remains unclear. A review of the current literature revealed 18 cases of White-Sutton syndrome with POGZ variants and congenital heart disease, and we summarize their clinical features in this study. CONCLUSIONS: Our findings based on the present case and those in the literature indicate a relationship between POGZ mutation and congenital heart disease.

The Removal of Pollutants from Wastewater Using Magnetic Biochar: A Scientometric and Visualization Analysis.

In recent years, the use of magnetic biochar in wastewater treatment has shown significant effects and attracted scholars' attention. However, due to the relatively short research time and the lack of systematic summaries, it is difficult to provide a more in-depth analysis. This study utilizes RStudio and CiteSpace software to comprehensively analyze the research trends and progress of magnetic biochar in wastewater treatment. The analysis of bibliometrics is performed on 551 relevant papers retrieved from the Web of Science, spanning the period between 2011 and 2022. The most influential countries, institutions, journals, disciplinary distribution, and top 10 authors and papers in this field have been identified. The latest dataset has been used for keyword clustering and burst analysis. The results indicated that: (1) Bin Gao is the most influential author in this field, and high-level journals such as Bioresource Technology are more inclined to publish articles in the field of magnetic biochar. (2) Research in this field has predominantly focused on the removal of heavy metals and organic compounds. Keyword burst analysis shows a shift in research direction towards the removal of complex organic pollutants recently. (3) For the future development of magnetic biochar, an environment-friendly approach, economic viability, and joint technology are the directions that need more exploration. Finally, this paper provides a summary of the various adsorption mechanisms of magnetic biochar and several common modification methods, aiming to assist scholars in their research endeavors.

Mosaicism in tuberous sclerosis complex: Lowering the threshold for clinical reporting.

Tuberous sclerosis complex (TSC) is a multi-system genetic disorder. Most patients have germline mutations in TSC1 or TSC2 but, 10%-15% patients do not have TSC1/TSC2 mutations detected on routine clinical genetic testing. We investigated the contribution of low-level mosaic TSC1/TSC2 mutations in unsolved sporadic patients and families with TSC. Thirty-one sporadic TSC patients negative on routine testing and eight families with suspected parental mosaicism were sequenced using deep panel sequencing followed by droplet digital polymerase chain reaction. Pathogenic variants were found in 22/31 (71%) unsolved sporadic patients, 16 were mosaic (median variant allele fraction [VAF] 6.8% in blood) and 6 had missed germline mutations. Parental mosaicism was detected in 5/8 families (median VAF 1% in blood). Clinical testing laboratories typically only report pathogenic variants with allele fractions above 10%. Our findings highlight the critical need to change laboratory practice by implementing higher sensitivity assays to improve diagnostic yield, inform patient management and guide reproductive counseling.

Association of Long-term Ambient Fine Particulate Matter (PM2.5) and Incident CKD: A Prospective Cohort Study in China.

RATIONALE & OBJECTIVE: Increasing evidence has linked ambient fine particulate matter (ie, particulate matter no larger than 2.5 µm [PM2.5]) to chronic kidney disease (CKD), but their association has not been fully elucidated, especially in regions with high levels of PM2.5 pollution. This study aimed to investigate the long-term association of high PM2.5 exposure with incident CKD in mainland China. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 72,425 participants (age ≥18 years) without CKD were recruited from 121 counties in Hunan Province, China. EXPOSURE: Annual mean PM2.5 concentration at the residence of each participant derived from a long-term, full-coverage, high-resolution (1 × 1 km2), high-quality dataset of ground-level air pollutants in China. OUTCOMES: Incident CKD during the interval between the baseline examination of each participant (2005-2017) and the end of follow-up through 2018. ANALYTICAL APPROACH: Cox proportional hazards models were used to estimate the independent association of PM2.5 with incident CKD and the joint association of PM2.5 with temperature or humidity on the development of PM2.5-related CKD. Restricted cubic splines were used to model exposure-response relationships. RESULTS: Over a median follow-up of 3.79 (IQR, 2.03-5.48) years, a total of 2,188 participants with incident CKD were identified. PM2.5 exposure was associated with incident CKD with an adjusted hazard ratio of 1.71 (95% CI, 1.58-1.85) per 10-µg/m3 greater long-term exposure. Multiplicative interactions between PM2.5 and humidity or temperature on incident CKD were detected (all P < 0.001 for interaction), whereas an additive interaction was detected only for humidity (relative risk due to interaction, 3.59 [95% CI, 0.97-6.21]). LIMITATIONS: Lack of information on participants' activity patterns such as time spent outdoors. CONCLUSIONS: Greater long-term ambient PM2.5 pollution is associated with incident CKD in environments with high PM2.5 exposure. Ambient humidity has a potentially synergetic effect on the association of PM2.5 with the development of CKD. PLAIN-LANGUAGE SUMMARY: Exposure to a form of air pollution known as fine particulate matter (ie, particulate matter ≤2.5 µm [PM2.5]) has been linked to an increased risk of chronic kidney disease (CKD), but little is known about how PM2.5 affects CKD in regions with extremely high levels of PM2.5 pollution. This longitudinal cohort study in China investigates the effect of PM2.5 on the incidence of CKD and whether temperature or humidity interact with PM2.5. Our findings suggest that long-term exposure to high levels of ambient PM2.5 significantly increased the risk of CKD in mainland China, especially in terms of cumulative average PM2.5. The associations of PM2.5 and incident CKD were greater in high-humidity environments. These findings support the recommendation that reducing PM2.5 pollution should be a priority to decrease the burden of associated health risks, including CKD.

Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study.

The aim of this study is to evaluate the diagnostic value of genome sequencing in children with epilepsy, and to provide genome sequencing-based insights into the molecular genetic mechanisms of epilepsy to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling. We performed genome sequencing on 320 Chinese children with epilepsy, and interpreted single-nucleotide variants and copy number variants of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analysed. Age at seizure onset ranged from 1 day to 17 years, with a median of 4.3 years. Pathogenic/likely pathogenic variants were found in 117 of the 320 children (36.6%), of whom 93 (29.1%) had single-nucleotide variants, 22 (6.9%) had copy number variants and two had both single-nucleotide variants and copy number variants. Single-nucleotide variants were most frequently found in SCN1A (10/95, 10.5%), which is associated with Dravet syndrome, followed by PRRT2 (8/95, 8.4%), which is associated with benign familial infantile epilepsy, and TSC2 (7/95, 7.4%), which is associated with tuberous sclerosis. Among the copy number variants, there were three with a length <25 kilobases. The most common recurrent copy number variants were 17p13.3 deletions (5/24, 20.8%), 16p11.2 deletions (4/24, 16.7%), and 7q11.23 duplications (2/24, 8.3%), which are associated with epilepsy, developmental retardation and congenital abnormalities. Four particular 16p11.2 deletions and two 15q11.2 deletions were considered to be susceptibility factors contributing to neurodevelopmental disorders associated with epilepsy. The diagnostic yield was 75.0% in patients with seizure onset during the first postnatal month, and gradually decreased in patients with seizure onset at a later age. Forty-two patients (13.1%) were found to be specifically treatable for the underlying genetic cause identified by genome sequencing. Three of them received corresponding targeted therapies and demonstrated favourable prognoses. Genome sequencing provides complete genetic diagnosis, thus enabling individualized treatment and genetic counselling for the parents of the patients. Genome sequencing is expected to become the first choice of methods for genetic testing of patients with epilepsy.

Anatomical Basis for Malar Augmentation Injection With the Zygomatic Ligamentous System.

BACKGROUND: The malar augmentation injection has gained popularity in recent years, but the exact location of each injection site has not been clearly identified. OBJECTIVE: To discover ideal injection sites by comprehensively considering the distributions of ligaments, muscles, and vessels. MATERIALS AND METHODS: Eighteen cadaver heads were dissected to investigate the zygomatic ligamentous system and to measure the position of muscles. Sixty-six cadaver heads were subjected to computed tomographic scanning and three-dimensional vessel reconstruction. Radiological evaluation of the fillers was performed before and after experimental injection in one hemiface and dissected to confirm safe delivery. Five patients were enrolled in a prospective clinical study. 2D and 3D photographs were taken before and after the injections for comparison. RESULTS: Site 1 was defined along the zygomatic arch, except the first 1/4 length and the midline of the arch. Site 2 was on the body of the zygoma, superior to the level of the infraorbital foramen and medial to the jugale. Site 3 was defined in the anteromedial midface approximately 30 mm below the lateral canthus. CONCLUSION: Injections at these 3 sites can be performed within the range of the ligaments to achieve effective lifting effects and minimize potential complications.

Extended Maxillary Osteotomy Guide: A Design That Allows Manipulation of the Osteotomy Direction on the Posterior and Inner Walls of the Maxilla.

PURPOSE: Design an extended osteotomy guide (EOG) for Le Fort I osteotomy to improve the safety of surgery. MATERIALS AND METHODS: The digital Le Fort I osteotomy guide was designed in MIMICS 23.0. Twenty-eight patients were randomized into 2 groups. Patients in the experimental group used EOG, and patients in the control group used a traditional osteotomy guide (TOG). Virtual designs and actual postoperative outcomes were compared by cone-beam computed tomography. The safety of the operation was confirmed by the accuracy of the osteotomy direction and depth on the inner and posterior walls of the maxilla. RESULTS: All positioning deviations of both osteotomy guides were <0.3 mm (P>0.05). The osteotomy depths on the inner and posterior walls with the EOG and TOG deviated by 0.789±1.179 and 1.811±1.345 mm (P=0.004) and 0.648±0.999 and 1.262±0.942 mm (P=0.030), respectively. The angles of deviation of the osteotomy direction on the inner and posterior walls by the EOG and TOG were 2.025±2.434 and 5.069±2.391 degrees (P<0.001) and 2.772±2.979 and 8.653±4.690 degrees (P<0.001), respectively. CONCLUSIONS: The EOG was more accurate than TOG for manipulating osteotomy direction and depth on the inner and posterior maxillary walls. Thus, EOG could ensure higher surgical safety than TOG.

The coupled reaction catalyzed by EchB and EchC lead to the formation of the common 2',3',5'-trihydroxy-benzene core in echosides biosynthesis.

p-Terphenyls represent a unique family of aromatic natural products generated by nonribosomal peptide synthetase-like (NRPS-like) enzyme. After formation of p-terphenyl skeleton, tailoring modifications will give rise to structural diversity and various biological activities. Here we demonstrated a two-enzyme (EchB, a short-chain dehydrogenase/reductase (SDR), and EchC, a nuclear transport factor 2 (NTF2)-like dehydratase) participated transformation from dihydroxybenzoquinone core to 2',3',5'-trihydroxy-benzene in the biosynthesis of echosides. Beginning with polyporic acid as substrate, successive steps of reduction-dehydration-reduction cascade catalyzed by EchB-EchC-EchB were concluded after in vivo gene disruption and in vitro bioassay experiments. These findings demonstrated a conserved synthesis pathway of 2',3',5'-trihydroxy-p-terphenyls in bacteria, such as Actinomycetes and Burkholderia. The parallel pathway in fungi has yet to be explored.

Detection of aerobe-anaerobe mixed infection by metagenomic next-generation sequencing in an adult suffering from descending necrotizing mediastinitis.

BACKGROUND: Descending necrotizing mediastinitis (DNM) is one of the most virulent forms of mediastinitis. The main causes of high mortality in DNM are believed to stem from difficulty and delay in the diagnosis. Fast and accurate identification of pathogens is important for the treatment of these patients. Metagenomics next-generation sequencing (mNGS) is a powerful tool to identify all kinds of pathogens, especially for rare and complex infections. CASE PRESENTATION: A 64-year-old male patient was admitted to the intensive care unit (ICU) with unconsciousness, dyspnea, and swelling in the mandible and neck. Computed tomography (CT) scan results combined with clinical laboratory examination indicated DNM. Vancomycin and imipenem were used, and vacuum sealing drainage was applied for debridement and drainage of the infected area. The positive mNGS results of drainage fluid confirmed the presence of mixed infection caused by Streptococcus anginosus, Prevotella oris, and several other anaerobes. The antibiotics were adjusted to piperacillin/tazobactam and tinidazole according to the mNGS results and antimicrobial susceptibility testing of cultured pathogens. After 11 days of antibiotic therapy, the infection symptoms of the neck and mediastinum improved, and the patient was transferred out of the ICU on the 26th day after negative result of drainage fluid culture. CONCLUSION: This case suggested that mNGS is a promising technology for precise and fast pathogens identification with high sensitivity, which may guide the diagnosis of infectious diseases in the future trend.

Energy delivery guided by indirect calorimetry in critically ill patients: a systematic review and meta-analysis.

BACKGROUND: The use of indirect calorimetry (IC) is increasing due to its precision in resting energy expenditure (REE) measurement in critically ill patients. Thus, we aimed to evaluate the clinical outcomes of an IC-guided nutrition therapy compared to predictive equations strategy in such a patient population. METHODS: We searched PubMed, EMBASE, and Cochrane library databases up to October 25, 2020. Randomized controlled trials (RCTs) were included if they focused on energy delivery guided by either IC or predictive equations in critically ill adults. We used the Cochrane risk-of-bias tool to assess the quality of the included studies. Short-term mortality was the primary outcome. The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity. RESULTS: Eight RCTs with 991 adults met the inclusion criteria. The overall quality of the included studies was moderate. Significantly higher mean energy delivered per day was observed in the IC group, as well as percent delivered energy over REE targets, than the control group. IC-guided energy delivery significantly reduced short-term mortality compared with the control group (risk ratio = 0.77; 95% CI 0.60 to 0.98; I2 = 3%, P = 0.03). IC-guided strategy did not significantly prolong the duration of mechanical ventilation (mean difference [MD] = 0.61 days; 95% CI - 1.08 to 2.29; P = 0.48), length of stay in ICU (MD = 0.32 days; 95% CI - 2.51 to 3.16; P = 0.82) and hospital (MD = 0.30 days; 95% CI - 3.23 to 3.83; P = 0.87). Additionally, adverse events were similar between the two groups. CONCLUSIONS: This meta-analysis indicates that IC-guided energy delivery significantly reduces short-term mortality in critically ill patients. This finding encourages the use of IC-guided energy delivery during critical nutrition support. But more high-quality studies are still needed to confirm these findings.

Cytotoxic and Anti-Inflammatory Sesquiterpenes from the Whole Plants of Centipeda minima.

Sixteen new sesquiterpene lactones (1-16) along with 13 known analogues (17-29) were isolated from the whole plants of Centipeda minima. The structures of 1-16 were delineated by the combination of NMR spectroscopic experiments, HRESIMS, single-crystal X-ray diffraction analyses, and ECD spectra. Compounds 23-26 showed potent cytotoxicity against Hela, HCT-116, and HepG2 cells with IC50 values of 0.8-2.6, 0.4-3.3, and 1.1-2.6 µM, respectively. Compounds 8, 15, and 24 exhibited significant inhibitory activity on the production of nitric oxide in the lipopolysaccharide-activated RAW 264.7 mouse macrophage cell line, with IC50 values ranging from 0.1 to 0.2 µM.

Injectable Filler Technique for Face Lifting Based on Dissection of True Facial Ligaments.

BACKGROUND: Strengthening weakened ligament tissues with injectable fillers to improve their supportive effect may achieve the aesthetic goal of face lifting. OBJECTIVES: The aim of the study was to design an injectable technique for enhancing the true facial ligaments and dissect the ligaments to provide anatomical guidance for effective injection. METHODS: Six true facial ligaments were chosen as target anatomical sites for injection. Specimens were dissected, and 3-dimensional (3D) images were reconstructed to confirm the exact location of each injection site and to confirm that the proposed injection routes will not cause dangerous vascular damage. A total of 5 patients received the injections; 3D images were taken before and after the injections for comparison and clinical outcome assessments. RESULTS: The injection technique was designed to target 6 true facial ligaments, as follows. Site 1 targeted the temporal ligamentous adhesion region to lift the lateral ends of the eyebrows. Site 2 targeted the region of the lateral orbital thickening to lift the lateral canthus. Site 3 and site 4 targeted the zygomatic retaining ligaments and zygomatic cutaneous ligaments, respectively, to augment the soft tissues of the midface. Site 5 targeted the region of the maxillary ligament to lessen the nasolabial folds, and site 6 targeted the mandibular ligament to reduce the marionette line. CONCLUSIONS: This site-specific injection technique targeting the true ligaments may lead to increased efficiency and accuracy of face rejuvenation and exert a lifting effect.

Injury-preconditioning secretome of umbilical cord mesenchymal stem cells amplified the neurogenesis and cognitive recovery after severe traumatic brain injury in rats.

Traumatic brain injury (TBI) is a dominant cause of death and permanent disability worldwide. Although TBI could significantly increase the proliferation of adult neural stem cells in the hippocampus, the survival and maturation of newborn cells is markedly low. Increasing evidence suggests that the secretome derived from mesenchymal stem cells (MSCs) would be an ideal alternative to MSC transplantation. The successive and microenvironmentally responsive secretion in MSCs may be critical for the functional benefits provided by transplanted MSCs after TBI. Therefore, it is reasonable to hypothesize that the signaling molecules secreted in response to local tissue damage can further facilitate the therapeutic effect of the MSC secretome. To simulate the complex microenvironment in the injured brain well, we used traumatically injured brain tissue extracts to pretreat umbilical cord mesenchymal stem cells (UCMSCs) in vitro and stereotaxically injected the secretome from traumatic injury-preconditioned UCMSCs into the dentate gyrus of the hippocampus in a rat severe TBI model. The results revealed that compared with the normal secretome, the traumatic injury-preconditioned secretome could significantly further promote the differentiation, migration, and maturation of newborn cells in the dentate gyrus and ultimately improve cognitive function after TBI. Cytokine antibody array suggested that the increased benefits of secretome administration were attributable to the newly produced proteins and up-regulated molecules from the MSC secretome preconditioned by a traumatically injured microenvironment. Our study utilized the traumatic injury-preconditioned secretome to amplify neurogenesis and improve cognitive recovery, suggesting this method may be a novel and safer candidate for nerve repair. Cover Image for this issue: doi: 10.1111/jnc.14741.