From Molecular to Behavior: Higher Order Occipital Cortex in Major Depressive Disorder.

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.

Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder.

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.

Respiratory Variations in Peak Peripheral Artery Velocities and Waveforms for Rapid Assessment of Fluid Responsiveness in Traumatic Shock Patients.

BACKGROUND This study aimed to assess the correlation between the variability of the end-inspiratory and end-expiratory blood flow waveform and fluid responsiveness (FR) in traumatic shock patients who underwent mechanical ventilation by evaluating peripheral arterial blood flow parameters. MATERIAL AND METHODS A cohort of 60 patients with traumatic shock requiring mechanical ventilation-controlled breathing received ultrasound examinations to assess the velocity of carotid artery (CA), femoral artery (FA) and brachial artery (BA). A rehydration test was performed in which of 250 mL of 0.9% saline was administered within 30 min between the first and second measurement of cardiac output by echocardiography. Then, all patients were divided into 2 groups, a responsive group (FR+) and a non-responsive group (FR-). The velocity of end-inspiratory and end-expiratory peripheral arterial blood flow of all patients was ultrasonically measured, and the variability were measured between end-inspiratory and end-expiratory. RESULTS The changes in the end-inspiratory and end-expiratory carotid artery blood flow velocity waveforms of the FR+ groups were significantly different from those of the FR- group (P<0.001). A statistically significant difference in ΔVmax (CA), ΔVmax (BA), and ΔVmax (FA) between these 2 groups was found (all P<0.001). The ROC curve showed that DVmax (CA) and ΔVmax (BA) were more sensitive values to predict FR compared to ΔVmax (FA). The sensitivity of ΔVmax (CA), ΔVmax (FA), and ΔVmax (BA) was 70.0%, 86.7%, and 93.3%, respectively. CONCLUSIONS The study showed that periodic velocity waveform changes in the end-inspiratory and end-expiratory peripheral arterial blood flow can be used for quick assessment of fluid responsiveness.

Synthetic Studies toward Bazzanin K: Regioselective and Chemoselective Three-Component Suzuki Coupling.

The terphenyl substructure of the chiral cyclophane natural product bazzanin K was constructed. The key step involved sequential Suzuki couplings of a nonsymmetric dibromobenzene, which can be performed as a two-step process or as a one-pot three-component coupling. The key step represented a regioselective coupling of a dibromobenzene, as well as a chemoselective coupling of phenyl bromides in the presence of phenyl chlorides. Terphenyl intermediates displayed atropdiastereoisomerism, and they were converted to a single phenanthrene target by way of ring-closing metathesis.

Total Synthesis of (-)-Cephalotaxine and (-)-Homoharringtonine via Furan Oxidation-Transannular Mannich Cyclization.

Homoharringtonine and its congener cephalotaxine were synthesized. Oxidative ring-opening of a furan unveils an amine-tethered dicarbonyl, which undergoes spontaneous transannular Mannich cyclization. The cascade builds the full cephalotaxine substructure in a single operation in 60 % yield. A Noyori reduction enabled synthesis of the title compounds with excellent enantioselectivity (krel =278).

Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis.

CONTEXT: Short-chain fatty acids (SCFAs) have been reported to be associated with the pathogenesis of irritable bowel syndrome (IBS), but the results are conflicting. OBJECTIVE: Here, a systematic review of case-control studies detecting fecal SCFAs in IBS patients compared with healthy controls (HCs) and self-controlled studies or randomized controlled trials (RCTs) investigating fecal SCFA alterations after interventions were identified from several databases. DATA SOURCES: A systematic search of databases (PubMed, Web of Science, and Embase) identified 21 studies published before 24 February 2023. Data extractions: Three independent reviewers completed the relevant data extraction. DATA ANALYSIS: It was found that the fecal propionate concentration in IBS patients was significantly higher than that in HCs, while the acetate proportion was significantly lower. Low-FODMAP diets significantly reduced the fecal propionate concentration in the IBS patients while fecal microbiota transplantation and probiotic administration did not significantly change the fecal propionate concentration or acetate proportion. CONCLUSIONS: The results suggested that the fecal propionate concentration and acetate proportion could be used as biomarkers for IBS diagnosis. A low-FODMAP diet intervention could potentially serve as a treatment for IBS while FMT and probiotic administration need more robust trials.

Mechanistic Insights of Copper Catalyzed Trifluoromethyl Aziridine Opening: Regioselective and Stereospecific Aryl Grignard Addition.

The copper catalyzed regioselective and stereospecific opening of CF3-aziridines is reported. This method focuses on the synthesis of α-CF3-ß-arylethylamines, which can be potential key intermediates in the synthesis of synthetic analogues and biologically active molecules. Density functional theory calculations reveal the nature of the active copper species and the role of the LiClMgX2 (X = Cl or I) as a Lewis acid. Further, the computed mechanism accounts for the high regioselectivity of this transformation.

Case report: Treatment-resistant depression with acute psychosis in an adolescent girl with Cushing's syndrome.

Cushing's syndrome (CS) is a rare disease with multiple somatic signs and a high prevalence of co-occurring depression. However, the characteristics of depression secondary to CS and the differences from major depression have not been described in detail. In this case, we report a 17-year-old girl with treatment-resistant depression with a series of atypical features and acute psychotic episodes, which is a rare condition secondary to CS. This case showed a more detailed profile of depression secondary to CS and highlighted the differences with major depression in clinical features, and it will improve insight into the differential diagnosis especially when the symptoms are not typical.

Mucin Binding Protein of Lactobacillus casei Inhibits HT-29 Colorectal Cancer Cell Proliferation.

Many Lactobacillus casei strains are reported to exhibit anti-proliferative effects on colorectal cancer cells; however, the mechanism remains largely unknown. While there has been considerable interest in bacterial small metabolites such as short chain fatty acids, prior reports suggested that larger-sized molecules mediate the anti-proliferative effect of L. casei. Here, other possible ways of communication between gut bacteria and its host are investigated. LevH1 is a protein displayed on the surface of L. casei, and its mucin binding domain is highly conserved. Based on previous reports that the cell-free supernatant fractions decreased colorectal cell proliferation, we cloned the mucin binding domain of the LevH1 protein, expressed and purified this mucin binding protein (MucBP). It has a molecular weight of 10 kDa, is encoded by a 250 bp gene, and is composed primarily of a ß-strand, ß-turns, and random coils. The amino acid sequence is conserved while the 36th amino acid residue is arginine in L. casei CAUH35 and serine in L. casei IAM1045, LOCK919, 12A, and Zhang. MucBP36R exhibited dose-dependent anti-proliferative effects against HT-29 cells while a mutation of 36S abolished this activity. Predicted structures suggest that this mutation slightly altered the protein structure, thus possibly affecting subsequent communication with HT-29 cells. Our study identified a novel mode of communication between gut bacteria and their host.

Key Influencing Factors and Optimization Strategy of Epidemic Resilience in Urban Communities-A Case Study of Nanjing, China.

COVID-19 has posed a significantly severe impact on both people's lives and the global economic development. Increasing the community epidemic resilience will considerably improve the national public health emergency response capacity from bottom to top. This study identifies the influencing factors of community epidemic resilience through systematic literature review under the 4R framework, then obtains the relationships of influencing factors through Interpretive structural model, and finally assesses the performance of epidemic resilience using PROMETHEE II method through empirical cases in Nanjing, China. The results show that: (1) Eight factors influencing the epidemic resilience of community are identified, and the economic level plays the root role; (2) Community epidemic resilience can be improved from robustness, rapidity, redundancy and resourcefulness aspects; (3) Through the empirical analysis, the epidemic resilience ranking of community can be displayed (Community D > T > S > F); (4) Additionally, the performance and sensitivity analysis of influencing factors in each community can be demonstrated. (5) Finally, four implications are proposed, namely, allocating public resources rationally, significantly increasing the economic level, ensuring the accuracy of information delivery and conducting disaster learning.

Research Progress and Improvement Ideas of Anti-Epidemic Resilience in China's Urban Communities.

In the post-epidemic era, China's urban communities are at the forefront of implementing the whole chain of accurate epidemic prevention and control. However, the uncertainty of COVID-19, the loopholes in community management and people's overly optimistic judgment of the epidemic have led to the frequent rebound of the epidemic and serious consequences. Existing studies have not yet formed a panoramic framework of community anti-epidemic work under the concept of resilience. Therefore, this article first summarizes the current research progress of resilient communities from three perspectives, including ideas and perspectives, theories and frameworks and methods and means, and summarizes the gap of the current research. Then, an innovative idea on the epidemic resilience of urban communities in China is put forward: (1) the evolution mechanism of community anti-epidemic resilience is described through the change law of dynamic networks; (2) the anti-epidemic resilience of urban communities is evaluated or predicted through the measurement criteria; (3) a simulation platform based on Multi-Agent and dynamic Bayesian networks simulates the interactive relationship between "epidemic disturbance-cost constraint--epidemic resilience"; (4) the anti-epidemic strategies are output intelligently to provide community managers with decision-making opinions on community epidemic prevention and control.

Modeling the occupational health risk of workers caused by environmental release during the production of PC components.

Prefabricated construction is one of the solutions to the problem of balancing environmental improvements with the new buildings in the construction industry. Some work originally done on site is transferred to the front end, and the occupational health risks to industrial workers during the production of prefabricate concrete components are thus aggravated. This study aims to propose a framework to simulate the occupational health risks of workers in prefabricate concrete component plants from the perspective of risk identification, risk assessment, and risk control. Through the following 4 steps, including environmental release monitoring, diffusion and human inhalation mechanism analysis, occupational health risk evaluation, and full-path health risk simulation, this study maps physical entities to virtual reality. The proposed method tends to address the root causes behind occupational health risks, such as the lack of measurement, assessment and prevention criteria, and providing new ideas for theoretical research and innovative practice of HSE management and risk management in the construction industry.

Efficacy and Safety of Remimazolam Besylate versus Dexmedetomidine for Sedation in Non-Intubated Older Patients with Agitated Delirium After Orthopedic Surgery: A Randomized Controlled Trial.

Purpose: The purpose of the present study was to investigate the efficacy and safety of remimazolam besylate compared with dexmedetomidine for the relief of agitated delirium in non-intubated older patients after orthopedic surgery. Patients and methods: Seventy-five patients were randomly divided into two groups. Patients assigned to the remimazolam group received a loading dose of 0.075 mg/kg remimazolam besylate over 1 minute, followed by a continuous infusion of 0.1 to 0.3 mg/kg/h. Subjects randomized to the dexmedetomidine group received a loading infusion of 0.5 µg/kg dexmedetomidine over 10 minutes, followed by a maintenance dose of 0.2 to 0.7 µg/kg/h. Meanwhile, RASS score-guided dose titration was followed. To assess the efficacy of the study drugs in terms of time to resolution of agitation, time to first achievement of target sedation, percentage of time within the target sedation range, and time to delirium resolution. Safety of the sedatives was evaluated by adverse events during hospitalization. Results: Time to resolution of agitation did not differ between the two groups. The time to first achievement of target sedation was 19.0 (9.5 to 31.0) minutes for remimazolam besylate vs 43.5 (15.0 to 142.5) minutes for dexmedetomidine (P < 0.001). Percentage of time within the target sedation range was 77.8% for remimazolam besylate-treated patients and 67.4% for dexmedetomidine-treated patients (P = 0.001). Patients in the remimazolam group had longer time to delirium resolution (29.5 [21.3 to 32.5] hours) than those in the dexmedetomidine group (22.8 [18.9 to 28.5] hours) (P = 0.042). Patients sedated with remimazolam besylate had more oversedation (P = 0.036) but less hypotension (P = 0.007). Conclusion: Compared with dexmedetomidine, remimazolam besylate was equally effective in relieving agitation, and resulted in earlier achievement of sedation goal and more controllable sedation. Remimazolam may be an ideal agent for obtaining rapid tranquillisation.

Copper Catalyzed Regioselective and Stereospecific Aziridine Opening with Pyridyl Grignard Nucleophiles.

Copper catalyzed regioselective and stereospecific coupling between aziridines and in situ generated pyridine Grignard reagents is reported. This method provides ß-pyridylethylamines with diverse structures and functionalities from aziridines and iodopyridines. ß-Pyridylethylamines are potential scaffolds for the synthesis of biologically active compounds often found in pharmaceuticals. The synthesis of challenging chiral dihydroazaindoles was also achieved through mild one-pot reaction conditions via aziridine opening followed by nucleophilic cyclization.

Rapid Eye Movement Sleep Deprivation Combined With Fluoxetine Protects Against Depression-Induced Damage and Apoptosis in Rat Hippocampi via A1 Adenosine Receptor.

Background: Rapid eye movement sleep deprivation (REMSD) and fluoxetine affect depression, yet the detailed molecular mechanisms were not clear. Methods: Rat depression chronic unpredictable stress was constructed, and the body weight of rats was measured. The efficacy of REMSD and fluoxetine on the pleasure experience, exploration, and cognition of rats with depression was determined by the Sucrose preference test, the open field test, and Morris water task, respectively. The effects of REMSD and fluoxetine on depression-induced damage and apoptosis in rat hippocampi were detected using hematoxylin-eosin staining and terminal transferase-mediated biotin 2'-deoxyuridine, 5'-triphosphate nick end labeling. A1 adenosine receptor content was measured by immunohistochemistry. Relative expressions of the A1 adenosine receptor, proteins related to apoptosis (B Bcl-2-associated X protein; B-cell lymphoma 2), phosphoinositide 3-kinase, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific two were quantified by quantitative real-time polymerase chain reaction and Western blot as needed. Results: Depression decreased rat weight. REMSD combined with fluoxetine increased body weight, prompted rat behavior, alleviated depression-induced damage, attenuated apoptosis, and promoted A1 adenosine receptor level in rat hippocampi. Furthermore, the combined therapy upregulated expressions of A1 adenosine receptor, B-cell lymphoma 2, and phosphoinositide 3-kinase but downregulated those of B-cell lymphoma 2-associated X protein, P38 mitogen-activated protein kinase, cFos, and adenosine deaminase RNA specific 2 in the hippocampi of rats with depression. Conclusion:REMSD combined with fluoxetine protected rats against depression-induced damage and apoptosis in the hippocampus via the A1 adenosine receptor, providing a possible treatment strategy for depression.

Melatonin ameliorated CUMS-induced depression-like behavior via restoring endoplasmic reticulum stress in rat hippocampus.

Melatonin is a hormone synthesized and secreted by the pineal gland with the effect of regulating sleep rhythm. Circadian and sleep disturbances may be central for understanding the pathophysiology and treatment of depression. Recently, the melatonergic system has been implicated in the pathophysiology and treatment of depression. In this study, we observed the effects of melatonin on depression-like behavior induced by chronic unpredictable mild stress (CUMS) in rats, and its molecular mechanism was explored. Adult male Sprague-Dawley rats were exposed to CUMS for 4 weeks. Melatonin or saline was injected intraperitoneally. Behavioral changes of Sprague-Dawley rats were detected by the open field test, sugar preference test, elevated O maze test and forced swimming test. In addition, the plasma corticosterone level and the expression of endoplasmic reticulum stress-related protein in the hippocampus of rats were measured. Compared with the control group, the CUMS-exposed Sprague-Dawley rats showed depression-like behavior, which was significantly improved by melatonin treatment. Moreover, CUMS induced endoplasmic reticulum stress and JNK phosphorylation in the hippocampus. Melatonin treatment could significantly reverse the endoplasmic reticulum stress and JNK phosphorylation induced by CUMS. These results suggest that melatonin improves depression-like behavior by inhibiting endoplasmic reticulum stress induced by CUMS. This study demonstrates that melatonin can improve depression-like behavior induced by CUMS, which may be related to the inhibition of endoplasmic reticulum stress and JNK phosphorylation in rat hippocampus.

The value of AGR2 and KRT5 as an immunomarker combination in distinguishing lung squamous cell carcinoma from adenocarcinoma.

With the advancement of tumor subtype-specific treatments, precise histopathologic distinction between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is of significant clinical importance. Nevertheless, the current markers are insufficiently precise in poorly differentiated tissue. This study aimed to establish a histology-specific immunomarker combination to subclassify non-small cell lung cancer (NSCLC) specimens. Based on previous work, we assessed the differential expression of anterior gradient 2 (AGR2) and keratin 5 (KRT5) in ADC and SCC by analyzing public datasets and postoperative specimens. Subsequently, we established a train set (n = 188) and a validation set (n = 42) comprised of NSCLC surgical specimens for training and verifying the subtype-identification capabilities of the two biomarkers separately and in combination, and contrasted the diagnostic utility of AGR2-KRT5 with that of the classic immunomarker combination, TTF1-P40. Differential expression of the two genes was statistically significant in ADC and SCC samples, both at the mRNA and protein levels. The specificity and sensitivity of AGR2 to detect ADC in the training set were 97.0% and 94.4%, while the sensitivity and specificity of KRT5 to determine SCC were 93.9% and 98.9%, respectively. The accuracies of AGR2-KRT5 in ADC, SCC, and across all samples were 93.3%, 92.0% and 92.6% respectively. In the validation cohort, the predictive accuracy of AGR2-KRT5 was up to 100% for ADC and 86.7% for SCC. Compared with TTF1-P40 in ADC samples, AGR2-KRT5 had 8.4% higher accuracy. In summary, the AGR2-KRT5 immunomarker combination reliably distinguished SCC from ADC, and was more accurate than TTF1-P40 in ADC.

[Measures and effects of schistosomiasis elimination in Wujin District, Changzhou City].

OBJECTIVE: To understand the measures and effects of schistosomiasis elimination in Wujin District, Changzhou City, so as to provide the reference for other similar areas. METHODS: The data of schistosomiasis prevention and control were collected and analyzed in Wujin District, Changzhou City from 1995 to 2015. RESULTS: From 1995 to 2015, the accumulated area for investigating Oncomelania hupensis snail habitats was 15 934.01 hm2 in Wujin District, and the accumulated area with snail habitats was 34.61 hm2, but no schistosome-infected snails were found. The area of snail control by molluscicides was 234.59 hm2, and the area of snail control by environmental reform was 84.48 hm2 in 18 key points. There were 259.3 thousand person-times receiving the examinations for schistosomiasis, and there were 17 314 head of livestock receiving the examinations for schistosomiasis, but no schistosome-infected cases were found. There were 204 2 person-times receiving the extensive chemotherapy. The popularizing rate of sanitary toilets was 99.25% in the whole district. The awareness rate of schistosomiasis control knowledge was 98.08% and the formation rate of proper behaviors was 97.82% in the population. CONCLUSIONS: In Wujin District, the aim of schistosomiasis elimination has been performed through the active control measures. However, there are still social and natural risk factors of re-endemic of schistosomiasis, and therefore, the schistosomiasis monitoring work still should be strengthened.

CSF miR-16 is decreased in major depression patients and its neutralization in rats induces depression-like behaviors via a serotonin transmitter system.

BACKGROUND: Animal and cell line studies demonstrated that miR-16 may be associated with major depressive disorder (MDD) via regulation of the expression of serotonin transporter (SERT) gene. However, human studies about miR-16 of patients with MDD are still lacking. The aim of this study was to investigate the possible involvement of miR-16 in the mechanism of MDD in humans. METHODS: Thirty-six drug-free patients with MDD and 30 healthy controls aged between 18 and 45 years old were recruited. 24-item Hamilton depression scale test was performed for each subject. MiR-16 in cerebrospinal fluid (CSF) and blood, as well as serotonin in CSF were assayed by the qRT-PCR or ELISA method. To confirm the role of CSF miR-16 in MDD, animal study about intracerebroventricular injection of anti-miR-16 was also performed. Depression-like behaviors, CSF miR-16 and serotonin, blood miR-16, and raphe SERT protein of rats were also tested. RESULTS: CSF miR-16 in MDD patients was significantly lower than that in controls. It was negatively correlated with Hamilton scores and positively associated with CSF serotonin. However, blood miR-16 was not significantly different between two groups and it was not statistically correlated with CSF miR-16. In animal study, anti-miR-16-treated rats were evaluated to exhibit depression-like behaviors, extremely lower CSF miR-16, significantly higher CSF serotonin, and obviously higher raphe SERT protein than control rats. LIMITATION: We did not detect SERT protein in human brain due to the impossibility of sample collection. CONCLUSION: Our study suggested that CSF miR-16 participated in the physiopathology of MDD via the modulation of serotonin transmitter system in brain.