Gut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids.

A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host-microbe interactions in the gut remain largely unknown. Here we report that the gut commensal Christensenella minuta modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of C. minuta alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for C. minuta and acylated bile acids in metabolic diseases.

Exploring the Effect of Anti-immigration Rhetoric on Emergency Department Use by Undocumented Adults.

An unwelcoming policy climate can create barriers to health care access and produce a 'Chilling Effect' among immigrant communities. For undocumented immigrants, barriers may be unique and have a greater impact. We used administrative emergency department (ED) data from 2015 to 2019 for a Midwestern state provided under a data use agreement with the state hospital association. General linear modelling was used to estimate the impact of anti-immigrant rhetoric on ED visit intensity among non-elderly adults who were likely Hispanic/Latino with undocumented status. Compared to 2015, the average ED visit intensity among adults who were likely Hispanic/Latino with undocumented status was significantly higher during 2016-2019 when anti-immigrant rhetoric was heightened. The magnitude of this change increased over time (0.013, 0.014, 0.021, and 0.020, respectively). Additionally, this change over time was not observed in the comparison groups. Our findings suggest that anti-immigrant rhetoric may alter health care utilization for adults who are likely Hispanic/Latino with undocumented status. Limitations to our findings include the use of only those likely to be Hispanic/Latino, data from only one Midwestern state and the loss of data due to non-classification using the NYU ED algorithm. Further research should focus on validating these findings and investigating these identification methods and anti-immigrant rhetoric effects among other undocumented groups including children and adults of different race or ethnicity such as black, both those that identify as Hispanic/Latino and those that do not. Developing strategies to improve health care access for undocumented Hispanic/Latino adults also warrants future research.

Fear of Deportation and Hispanic Early Adolescent Substance Use: a Moderated Mediation Model of Stress and Hope.

Reports of deportation can create a state of chronic fear in children living in mixed-status immigrant families over their own or a loved one's potential deportation. One indicator of health disparities among youth is elevated rates of alcohol, tobacco, and other drug use (ATOD). Yet little is known about the effects of fear of deportation (FOD) on ATOD or what might promote resilience. We explore the associations between FOD and ATOD use, how stress mediates this relationship, and whether hope moderates the mediated pathway from FOD to ATOD. Participants were 200 first- and second-generation 7th grade Hispanic youth (49% female) assessed across three waves of data. A moderated mediation model tested the indirect effect of FOD on ATOD through stress and whether hope moderated these associations. FOD was measured by the Family Fear of Deportation Scale. Snyder's Children's Hope Scale measured hope. Stress was measured by a short version of Pediatric Psychological Stress Measure. ATOD was adapted from the Monitoring the Future project. FOD was not directly associated with ATOD use. However, this path was fully mediated by stress. Hope significantly moderated the path from FOD to stress such that a one unit increase in hope completely offset the effects of FOD on stress. Hope did not moderate the path from stress to ATOD use. Interventions that increase awareness of deportation trauma, alleviate stress, and promote hope may help prevent, delay initiation into, and/or decrease ATOD among Hispanic first- and second-generation youth.

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

Research progress in the application of proteomics technology in brain injury.

The aim of this article is to review the application progress of proteomics technology in brain injury research in recent years, point out the current problems that need to be overcome, and explore the application prospects of proteomics analysis in brain injury. This study also aims to retrieve all literature on brain injury and proteomics and summarize it. Through searching and screening, the widespread application of proteomics technology in the treatment of traumatic brain injury (TBI) and the use of a large number of TBI biomarkers were discovered. The pathways mediated by some biomarkers and the physiological and pathological mechanisms of occurrence were elucidated. The current classification of brain injury is mainly based on subjective evaluation of clinical symptoms, combined with objective imaging. However, its practical value is often limited when applied to prognosis evaluation in brain injury. Proteomics technology can make up for this deficiency and provide a reference for the prevention and treatment of brain injury.

Hydrophilic magnetic Ti3C2Tx-based nanocomposite as an efficient boron adsorbent: Synthesis, characterization, and application.

It is widely recognized that wastewater containing boron is an environmental issue. Therefore, the development of adsorbents with excellent adsorption capacity, stability, and recyclability is essential in water treatment applications. A Fe3O4/PDA/Ti3C2Tx/PEI/DHHA nanocomposite has been prepared that can be used to separate and recover boric acid by adjusting the pH of the solution, based on the affinity theory of boric acid and cis-diol. Through series characterization, it was determined that the adsorbent possessed good magnetic properties, high hydrophilicity and high loading capacities. In this study, 4-formylphenylboronic acid (FPBA) was selected as the model compound. The nanocomposite exhibited an adsorption equilibrium time of 10 h and an adsorption capacity of 98.99 mg/g at pH = 8.5 and 25 °C. The Langmuir isothermal model and the quasi-secondary kinetic model are both appropriate for describing the adsorption process. Thermodynamic results suggest that adsorption is a spontaneous chemisorption process. Furthermore, the nanocomposite retains good regeneration performance after five adsorption-desorption cycles.

Safety and effectiveness of rehabilitation training for stroke complicated with muscular call vein thrombosis: An observational study.

This study aimed to explore the safety and effectiveness of rehabilitation treatment for stroke patients with muscular call vein thrombosis (MCVT) in the lower limbs. A total of 173 patients were recruited with stroke complicated by MCVT, including 130 who received rehabilitation training and 43 who did not receive rehabilitation training. The t test and chi-square test were used to analyze the basic data of the 2 groups. There were no significant differences in the Fugl-Meyer Assessment scores between 2 groups at the beginning of recruitment (P = .149). There was a significant difference in the Fugl-Meyer Assessment scores of the lower limbs in patients with MCVT after 3 weeks of rehabilitation treatment (P < .001), and there was a significant difference in the rate of MCVT recanalization and extension between the 2 groups (χ2 = 11.646, P = 0001). Combined with anticoagulation therapy, rehabilitation training did not increase the thrombosis progression of MCVT and was effective in the recovery of lower limb motor function in stroke patients.

Evaluation of Recovery Efficacy of Inspiratory Muscle Training After Lobectomy Based on Computed Tomography 3D Reconstruction.

BACKGROUND: Progressive resistance inspiratory muscle training is the principle of inspiratory air-flow resistance loading training to restore diaphragm function, increase alveolar compliance, and further improve respiratory function. However, there is a lack of research on the effectiveness of progressive resistance inspiratory training in post-lobectomy rehabilitation and the accurate assessment of lung volumes. METHODS: In this study, 79 subjects diagnosed with lung cancer and undergoing thoracoscopic lobectomy were retrospectively analyzed. The subjects were divided into a control group (n = 40) and an observation group (n =39) according to the different training modalities. The control group received conventional respiratory training. The observation group received progressive resistance inspiratory muscle training based on conventional breathing training. The primary outcome indicators were the following: lung function and lung volume. The secondary outcome indicators were the following: the number of postoperative hospital days, duration of drain retention, and incidence of postoperative pulmonary complications. RESULTS: Baseline data on age, sex, body mass index, smoking history, education level, underlying disease, type of pathology, lung cancer stages, surgical site, preoperative lung volume, and preoperative lung function were not statistically different between the 2 groups (P > .05). The subjects in the observation group had median (interquartile range [IQR]) lung volumes at 1 month after surgery (3.22 [3.12-3.37] L vs 3.14 [2.95-3.24] L; P = .031), median (IQR) FEV1 (2.11 [1.96-2.21] L vs 2.01 [1.81-2.12] L; P = .031), and mean ± SD peak expiratory flow (5.07 ± 0.62 L/s vs 4.66 ± 0.64 L/s; P = .005) were higher than those in the control group. The median (IQR) postoperative hospital stays (5 [4-5] d vs 5 [4-6] d; P = .030) and the median (IQR) chest drain retention times were shorter in the observation group versus the control group (74 [72-96] h vs 96 [84-96] h; P = .02). There was no significant difference in the incidence of postoperative atelectasis (5.1% vs 10.0%; P = .41) and pneumonia (7.7% vs 12.5%; P = .48). CONCLUSIONS: Progressive resistance inspiratory muscle training was effective in improving lung volume and lung function, and in reducing the length of hospital stay and chest drain closure time after lobectomy.

First-in-human application of double-stranded RNA bacteriophage in the treatment of pulmonary Pseudomonas aeruginosa infection.

A double-stranded RNA (dsRNA) phage phiYY is able to kill a pyomelanin-producing Pseudomonas aeruginosa strain, which was isolated from a 40-year-old man with interstitial lung disease (ILD) and chronic lung infection. Phage therapy was used as a last resort for this patient. The three-course nebulized phiYY treatment was used to reduce the bacterial burden and clinical symptoms of the patient. Recurrences of P. aeruginosa infections were observed 1-3 days post phage therapy. The recurrent isolates exhibited distinct antibiotic-susceptibility profiles compared with the original strain yet were still susceptible to phiYY. This assay represents the application of dsRNA phage in the treatment of chronic lung infection, albeit the safety and efficacy of the dsRNA phage require further assessment.

Fabrication of an Ag-based SERS nanotag for histamine quantitative detection.

A crucial issue in analytical science and physiology is the detection of histamine with high sensitivity, specificity and credibility, which served as an important neurotransmitter in biofluids. Despite the high sensitivity of surface-enhanced Raman spectroscopy (SERS) at the level of single molecule, there are still challenges in providing high sensitivity for histamine with a small cross section. For the selective detection of histamine using SERS, a highly sensitive sandwich structure substrate combining Fe3O4 and an Ag-based SERS nanotag was developed. The Fe3O4@SiO2-COOH served as a capture component for enriching histamine. Upon functionalized Ag nanoparticles with glycine (Gly) and (3-Aminopheyonyl) boronic acid (APBA), they were then used to connect with histamine and serve as a SERS nanotag, respectively. A linear relationship between the Raman intensity and the histamine concentration was observed over the range 10-4-10-8 M with a limit of detection of 7.24 × 10-9 M. This methodology also exhibited good selectivity in the presence of other neurotransmitters. With our new approach, histamine can be detected sensitively and reliably in fish samples, which indicates the potential prospect of an effective method for analyzing histamine in complex specimens.

Economic Pressure and Parent Acculturative Stress: Effects on Rural Midwestern Low-Income Latinx Child Behaviors.

Contrary to the visible Latinx population growth in rural America, rural Latinx households have experienced far greater economic disparities compared to Whites. Family economic stress predicts parents' emotional distress, lower family functioning, and places children at high risk for behavior problems. However, few studies have examined the combined effects of economic and acculturative stress on rural Latinx child behaviors, nor the family stress process among rural Latinx immigrant families in the Midwest, a new settlement area for Latinx and other immigrants (Kandel & Cromartie, 2004). Guided by the family stress model (FSM), we examined the relationships among economic pressure, parent acculturative stress, maternal depressive symptoms, parenting competence and child internalizing and externalizing behaviors using a sample of 148 rural low-income Latinx immigrant mothers in a Midwestern state. Structural equation modeling was performed to test these relationships. Results revealed that higher levels of economic pressure and parent acculturative stress were related to higher levels of maternal depressive symptoms, which in turn were associated with lower parenting competence and eventually linking to higher levels of child externalizing behaviors. Maternal depressive symptoms were positively associated with child internalizing behaviors. Parent acculturative stress was also found to be directly linked to child internalizing and externalizing behaviors. Intervention programs that aim to promote health and well-being among rural Latinx immigrant mothers and their children may find it beneficial to incorporate information and strategies that lessen parent acculturative stress and depression, promote parenting competence, and connect families to resources to help reduce economic pressure.

Gut microbial signatures and differences in bipolar disorder and schizophrenia of emerging adulthood.

INTRODUCTION: Gut microbial disturbance has been established as potential pathogenesis of mental disorders. However, the signatures and differences regarding patients with schizophrenia (SCH) or bipolar disorder (BD) in emerging adulthood as well as their subtypes have been poorly addressed. METHODS: In the present study, stool samples obtained from 63 emerging adult patients with schizophrenia (SCH), 50 with bipolar disorder (BD), and 40 healthy controls (HC) were analyzed by 16 S rRNA gene sequencing; psychiatric symptoms and psychological, social, and professional functioning were also assessed. RESULTS: We found that gut microbiota composition was remarkably changed in the patients with SCH and BD. Moreover, the distinct gut microbiome signatures and their potential function in bipolar depression (BP-D) and SCH with predominantly negative symptoms (SCH-N) as well as bipolar mania (BP-M) and SCH with predominantly positive symptoms (SCH-P) were also observed. Furthermore, we identified diagnostic potential biomarkers that can distinguish BD from HC (38 genera, AUC = 0.961), SCH from HC (32 genera, AUC = 0.962), and BD from Scheme (13 genera, AUC = 0.823). Potential diagnostic biomarkers that can distinguish BD-D from SCH-N (16 genera, AUC = 0.969) and BD-M from SCH-P (31 genera, AUC = 0.938) were also identified. CONCLUSION: This study provides further understanding of abnormal gut microbiome in emerging adulthood patients with SCH and BD and lay the potential foundation for the development of microbe-based clinical diagnosis for BD and SCH.

Spectrophotometric Detection of the BRCA1 Gene via Exponential Isothermal Amplification and Hybridization Chain Reaction of Surface-Bound Probes.

In this work, we demonstrated an ultrasensitive approach with a dual-amplification strategy for DNA assay based on isothermal exponential amplification (EXPAR) and the hybridization chain reaction (HCR). In the presence of target DNA, the hairpin probe DNA (HP1) recognized and partially hybridized with the target DNA to form double-stranded structures containing the full recognition sequences for nicking endonuclease and then initiated EXPAR. Under the reaction of EXPAR, a large number of single-stranded DNA (ssDNA) was produced in the circle of nicking, polymerization, and strand displacement. The resulting ssDNA can bind to the surface-bound probe on the well of the microplate and trigger the hybridization chain reaction, resulting in the production of numerous double-stranded DNA concatamers with biotin labeling. In the presence of streptavidin-conjugated horseradish peroxidase (HRP), the amplified signal can be detected by a spectrophotometer via HRP-catalyzed substrate 3,3'5,5'-tetramethylbenzidine (TMB). This proposed dual-amplification method provides a detection limit of 74.48 aM, which also exhibits good linearity ranging from 0.1 fM to 100 pM.

Pediatric acute myeloid leukemia patients with i(17)(q10) mimicking acute promyelocytic leukemia: Two case reports.

BACKGROUND: Chromosome i(17)(q10) abnormality is mainly associated with chronic myeloid leukemia (CML), myelodysplastic syndrome/myeloproliferative tumors (MDS/MPD), and acute myeloid leukemia (AML). The role of i(17)(q10) in AML is still unknown, the differences between AML and acute promyelocytic leukemia (APL)-like AML with i(17)(q10) need more research. This study aimed to investigate the clinical characteristics and laboratory evidence of 2 AML cases with i(17)(q10), similar to APL phenotype. CASE SUMMARY: Both pediatric patients were males; case 1 had newly diagnosed AML, and case 2 showed relapsed tumor after 1 year of drug withdrawal. Bone marrow cell morphology, chromosome karyotype analysis, Fully-instrumented submersible housing test, immunological assays, molecular biological methods, and blood tumor panoramic gene test were performed. All-trans retinoic acid (ATRA) combined with arsenic acid (As2O3) were used in the first course of treatment. Bone marrow was dominated by abnormal promyelocytic granulocytes. Karyotype test revealed i(17)(q10) isochromosome. Immunological phenotype mainly included positive expressions of CD9, CD13, CD33, and CD38. Case 1 suffered intracranial hemorrhage after re-chemotherapy and died on D162. For case 2, on D145 and D265, bone marrow promyelocytic granulocytes accounted for 2%. Flow cytometric residual lesion detection showed no abnormal immunophenotype cells. The copy number of WT1 gene in two cases were 1087 and 1010, respectively, and the expression rates were 55.29% and 59.5%, respectively. CONCLUSION: ATRA, As2O3, and chemotherapy may be ineffective in treating APL-like AML with i(17)(q10) but without t(15;17) and PML-RARA fusion gene.

Comprehensive RNA-seq reveals molecular changes in kidney malignancy among people living with HIV.

To heighten the awareness of kidney malignancy in patients with HIV infection to facilitate the early diagnosis of kidney cancer, the differentially expressed mRNAs were analyzed in this malignant tumor using RNA sequencing. We identified 2,962 protein-coding transcripts in HIV-associated kidney cancer. KISS1R, CAIX, and NPTX2 mRNA expression levels were specifically increased in HIV-associated kidney cancer while UMOD and TMEM213 mRNA were decreased in most cases based on real-time PCR analyses. These findings were similar to those noted for the general population with renal cell carcinoma. Immunohistochemical staining analysis also showed that a total of 18 malignant kidney cases among the people living with HIV (PLWH) exhibited positive staining for KISS1R and CAIX. Pathway analysis of the differentially expressed mRNAs in HIV-associated kidney cancer revealed that several key pathways were involved, including vascular endothelial growth factor-activated receptor activity, IgG binding, and lipopolysaccharide receptor activity. Altogether, our findings reveal the identified molecular changes in kidney malignancy, which may offer a helpful explanation for cancer progression and open up new therapeutic avenues that may decrease mortality after a cancer diagnosis among PLWH.

Acupuncture for Female Infertility: Discussion on Action Mechanism and Application.

A higher incidence of female infertility has been reported with an unexpectedly early appearance in recent years. The female infertility treatment and application of assisted reproductive technology have recently gained immense interest from scientists. Many studies have discussed the beneficial effects of acupuncture on female infertility. With advancements in science and medical technology, acupuncture-related research has increased in investigating its effectiveness in treating female infertility. This review focuses on a compilation of research in recent years on acupuncture for female infertility treatment and the exploration of the underlying mechanism. For this purpose, literature was searched using various search engines like PubMed, Web of Science, and Google Scholar. The search was refined by only focusing on recent studies on acupuncture effectiveness and mechanism in female infertility and evaluating pregnancy outcomes.

[Influence of coexisting components in Coptidis Rhizoma on excretion of magnoflorine in rat bile, urine, and feces].

Magnoflorine is an important aporphine alkaloid in Coptidis Rhizoma. As reported previously, coexisting components in Coptidis Rhizoma can change the pharmacokinetic characteristics of magnoflorine. To illustrate the interactional links of magnoflorine with its coexisting components in Coptidis Rhizoma, the present study investigated the influence of coexisting components in Coptidis Rhizoma on the excretion of magnoflorine in rat bile, urine, and feces. The rats were dosed with magnoflorine(30 mg·kg~(-1)) and water decoction of Coptidis Rhizoma(equivalent to 30 mg·kg~(-1) magnoflorine) via intragastric administration, and magnoflorine(10 mg·kg~(-1)) by intravenous administration, respectively, and the excretion of magnoflorine in rat bile, urine, and feces in 24 h was observed. The excretion rates of magnoflorine in bile and urine in 24 h were 0.90% and 37.11% respectively after intravenous administration of magnoflorine, which suggested that urination was the main excretive way of magnoflorine. The excretion rates of magnoflorine in feces were 8.77% and 6.18% respectively after intragastric administration of magnoflorine and water decoction of Coptidis Rhizoma, which indicated that defecation was the main excretion route of magnoflorine. The cumulative excretion rates of magnoflorine in the bile, urine, and feces in the Coptidis Rhizoma water decoction group were 77.78%, 79.44%, and 70.47% of those in the magnoflorine group. The results showed that the cumulative excretion rates of magnoflorine in rat bile, urine, and feces were not high, suggesting that magnoflorine was metabolized significantly in rats. The coexisting components of Coptidis Rhizoma could inhibit the excretion of magnoflorine in rat bile, urine, and feces, which was consistent with the decrease in the elimination rate of magnoflorine in the pharmacokinetics of Coptidis Rhizoma water decoction. It indicated interactions between drugs. This study is expected to provide references for the development of magnoflorine-containing new drugs and rational clinical medication of Coptidis Rhizoma.

Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants.

SARS-CoV-2 and its variants, such as the Omicron continue to threaten public health. The virus recognizes the host cell by attaching its Spike (S) receptor-binding domain (RBD) to the host receptor, ACE2. Therefore, RBD is a primary target for neutralizing antibodies and vaccines. Here, we report the isolation and biological and structural characterization of a single-chain antibody (nanobody) from RBD-immunized alpaca. The nanobody, named DL28, binds to RBD tightly with a K D of 1.56 nM and neutralizes the original SARS-CoV-2 strain with an IC50 of 0.41 µg mL-1. Neutralization assays with a panel of variants of concern (VOCs) reveal its wide-spectrum activity with IC50 values ranging from 0.35 to 1.66 µg mL-1 for the Alpha/Beta/Gamma/Delta and an IC50 of 0.66 µg mL-1 for the currently prevalent Omicron. Competition binding assays show that DL28 blocks ACE2-binding. However, structural characterizations and mutagenesis suggest that unlike most antibodies, the blockage by DL28 does not involve direct competition or steric hindrance. Rather, DL28 may use a "conformation competition" mechanism where it excludes ACE2 by keeping an RBD loop in a conformation incompatible with ACE2-binding.

Implementation of sodium alginate-Fe3O4 to localize undiagnosed small pulmonary nodules for surgical management in a preclinical rabbit model.

Many methods are used to locate preoperative small pulmonary nodules. However, deficiencies of complications and success rates exist. We introduce a novel magnetic gel for small pulmonary nodules localization in rabbit model, and furtherly evaluate its safety and feasibility. Rabbits were used as the experimental objects. A magnetic gel was used as a tracer magnet, mixed as sodium alginate-Fe3O4 magnetic fluid and calcium gluconate solution. In short-term localization, a coaxial double-cavity puncture needle was applied to inject the gel into the lung after thoracotomy, and a pursuit magnet made of Nd-Fe-B permanent magnetic materials was used to attract the gel representing location of the nodule. In long-term localization, the gel was injected under X-ray guidance. Imaging changes to the lung were observed under X-ray daily. Thoracotomy was performed to excise tissue containing the gel, and hematoxylin-eosin staining was used to observe the tissue on postoperative days 1, 3, 5, and 7. Observe tissues morphology of heart, liver, spleen, and kidney in the same way. The gel was formed after injection and drew lung tissue to form a protrusion from the lung surface under the applied magnetic field. No complication was observed. The shape and position of the gel had not changed when viewed under X-ray. Pathological analysis showed the gel had a clear boundary without diffusion of magnetic fluid. All tissues retained good histologic morphology and no magnetic fluid was observed. Our study preliminarily suggested that the technique using sodium alginate-Fe3O4 magnetic gel to locate small pulmonary nodules with guidance of X-ray, and to search for them under an applied magnetic field during the operation is safe and feasible.