Neuromodulation treatments for post-traumatic stress disorder: A systematic review and network meta-analysis covering efficacy, acceptability, and follow-up effects.

Neuromodulation treatments are novel interventions for post-traumatic stress disorder (PTSD), but their comparative effects at treatment endpoint and follow-up and the influence of moderators remain unclear. We included randomized controlled trials (RCTs) that explored neuromodulation, both as monotherapy and in combination, for treating patients with PTSD. 21 RCTs with 981 PTSD patients were included. The neuromodulation treatment was classified into nine protocols, including subtypes of transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), cervical vagal nerve stimulation (VNS), and trigeminal nerve stimulation (TNS). This Bayesian network meta-analysis demonstrated that (1) dual-tDCS (SMD = -1.30), high-frequency repetitive TMS (HF-rTMS) (SMD = -0.97), intermittent theta burst stimulation (iTBS) (SMD = -0.93), and low-frequency repetitive TMS (LF-rTMS) (SMD = -0.76) were associated with significant reductions in PTSD symptoms at the treatment endpoint, but these effects were not significant at follow-up; (2) no difference was found between any active treatment with sham controls; (3) regarding co-morbid additions, synchronized TMS (sTMS) was significantly associated with reductions of depression symptoms at treatment endpoint (SMD = -1.80) and dual-tDCS was associated with reductions in anxiety symptoms at follow-up (SMD = -1.70). Findings suggested dual-tDCS, HF-rTMS, iTBS, and LF-rTMS were effective for reducing PTSD symptoms, while their sustained efficacy was limited.

The Rejuvenation Effect of Bio-Oils on Long-Term Aged Asphalt.

Generally, rejuvenators are used to supply missing components of aged asphalt, reverse the aging process, and are widely used in asphalt maintenance and recycling. However, compared with traditional rejuvenators, bio-oil rejuvenators are environmentally friendly, economical and efficient. This study looks into the effect of the three different bio-oils, namely sunflower oil, soybean oil, and palm oil, on the physical properties, rheological properties and chemical components of aged asphalt at different dosages. The asphalt physical properties and Dynamic Shear Rheological (DSR) test results show that with the increase in bio-oil, the physical properties and rheological properties of rejuvenated asphalt are close to those of virgin asphalt, but the high-temperature rutting resistance needs to be further improved. The results of Fourier Transform Infrared Spectroscopy (FTIR) show that the carbonyl and sulfoxide indices of rejuvenated asphalt are much lower than those of aged asphalt. Moreover, the rejuvenation efficiency of aged asphalt mixed with sunflower oil is better than that with soybean oil and palm oil at the same dosage.

The de novo missense mutation F224S in GABRB2, identified in epileptic encephalopathy and developmental delay, impairs GABAAR function.

Genetic variants in genes encoding subunits of the γ-aminobutyric acid-A receptor (GABAAR) have been found to cause neurodevelopmental disorders and epileptic encephalopathy. In a patient with epilepsy and developmental delay, a de novo heterozygous missense mutation c.671 T > C (p.F224S) was discovered in the GABRB2 gene, which encodes the ß2 subunit of GABAAR. Based on previous studies on GABRB2 variants, this new GABRB2 variant (F224S) would be pathogenic. To confirm and investigate the effects of this GABRB2 mutation on GABAAR channel function, we conducted transient expression experiments using GABAAR subunits in HEK293T cells. The GABAARs containing mutant ß2 (F224S) subunit showed poor trafficking to the cell membrane, while the expression and distribution of the normal α1 and γ2 subunits were unaffected. Furthermore, the peak current amplitude of the GABAAR containing the ß2 (F224S) subunit was significantly smaller compared to the wild type GABAAR. We propose that GABRB2 variant F224S is pathogenic and GABAARs containing this ß2 mutant reduce response to GABA under physiological conditions, which could potentially disrupt the excitation/inhibition balance in the brain, leading to epilepsy.

[Research progress in molecular pharmacognosy of Andrographis paniculata].

Molecular pharmacognosy as an emerging interdisciplinary subject based on molecular biology and Chinese materia medica aims to study the synthesis and molecular regulation of secondary metabolites in medicinal plants. Andrographis Herba, the dried aboveground part of Andrographis paniculata, has liver-protecting, bile secretion-promoting, heat-clearing, toxin-removing, antimicrobial, and anti-inflammatory effects. The quality instability caused by plant varieties, environment, and technology in the production of A. paniculata is a limiting factor for the sustainable development of this industry. Based on the research methods of molecular pharmacognosy and omics, the regulation of secondary metabolites of A. paniculata has become the key solution to the quality problems of A. paniculata. This paper summarized the recent research achievements in the molecular pharmacognosy of A. paniculata, including molecular identification of the resources, genetic diversity, multi-omics, biosynthesis of active compounds, and germplasm resource innovation, and prospected the future development trend in this field. In-depth research of molecular pharmacognosy of A. paniculata will provide more scientific and effective technical support for the development of its medicinal value, give new insights into the cultivation of new A. paniculata varieties, and promote the high-quality sustainable development of this industry.

Safety of one 8.5-Fr pigtail catheter for postoperative continuous open gravity drainage after uniportal video-assisted thoracoscopic surgery pneumonectomy.

OBJECTIVES: Uniportal video-assisted thoracoscopic surgery pneumonectomy (U-VATS-P) is feasible and safe from a perioperative standpoint. How to choose the proper chest tube and drainage method is important in enhanced recovery after surgery (ERAS) protocols. In this study, we aimed to assess the safety of one 8.5-Fr (1Fr = 0.333 mm) pigtail catheter for postoperative continuous open gravity drainage after U-VATS-P. METHODS: We retrospectively reviewed a single surgeon's experience with U-VATS-P for lung cancer from May 2016 to September 2022. Patients were managed with one 8.5-Fr pigtail catheter for postoperative continuous open gravity drainage after U-VATS-P. The clinical characteristics and perioperative outcomes of the patients were retrospectively analyzed. RESULTS: In total, 77 patients had one 8.5-Fr pigtail catheter placed for postoperative continuous open gravity drainage after U-VATS-P for lung cancer. The mean age was 60.9±7.39 (40-76) years; The mean FEV1 was 2.1±0.6 (l/s), and the mean FEV1% was 71.2±22.7. The median operative time was 191.38±59.32 min; the mean operative hemorrhage was 109.46±96.56 ml; the mean duration of postoperative chest tube drainage was 6.80±2.33 days; the mean drainage volumes in the first three days after operation were 186.31±50.97, 321.97±52.03, and 216.44±35.67 ml, respectively; and the mean postoperative hospital stay was 7.90±2.58 days. No patient experienced complications resulting from chest tube malfunction. Ten patients experienced minor complications. One patient with nonlife-threatening empyema and bronchopleural fistula required short rehospitalization for anti-inflammatory therapy and reintubation. Three patients with chylothorax were treated with intravenous nutrition. Four patients had atrial fibrillation that was controlled by antiarrhythmic therapy. Two patients had more thoracic hemorrhagic exudation after the operation, which was found in time and was cured effectively, so they were discharged from the hospital uneventfully after early hemostatic therapy and nutritional support. CONCLUSIONS: All patients in this study received early postoperative rehabilitation, and the rate of relevant complications was low. We therefore recommend a single 8.5-Fr pigtail catheter for postoperative continuous open gravity drainage as an effective, safe and reliable drainage method for the management of U-VATS-P.

Mechanistic insights into phosphoactivation of SLAC1 in guard cell signaling.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.

Regulation and mechanism of enzyme metabolism in germinated hemp seeds by ultrasound combined with exogenous calcium chloride treatment.

γ-aminobutyric acid (GABA) plays an important role in anti-anxiety by inhibiting neurotransmitter in the central nervous system (CNS) of mammals, which is generated in the germinating seeds. The key enzymes activity of GABA metabolism pathway and nutrients content in hemp seeds during germination were studied after treated with ultrasound and CaCl2. The mechanism of exogenous stress on key enzymes in GABA metabolism pathway was investigated by molecular dynamics simulation. The results showed that ultrasonic combined with 1.5 mmol·L-1CaCl2 significantly increased the activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) in seeds, and promoted the conversion of glutamate to GABA, resulting in the decrease of glutamate content and the accumulation of GABA. Molecular dynamics simulations revealed that Ca2+ environment enhanced the activity of GAD and GABA-T enzymes by altering their secondary structure, exposing their hydrophobic residues. Ultrasound, germination and CaCl2 stress improved the nutritional value of hemp seeds.

MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network.

The membrane-associated RING-CH 8 protein (MARCH8), a member of the E3 ubiquitin ligase family, has broad-spectrum antiviral activity. However, some viruses hijack MARCH8 to promote virus replication, highlighting its dual role in the viral lifecycle. Most studies on MARCH8 have focused on RNA viruses, leaving its role in DNA viruses largely unexplored. Pseudorabies virus (PRV) is a large DNA virus that poses a potential threat to humans. In this study, we found that MARCH8 inhibited PRV replication at the cell-to-cell fusion stage. Interestingly, our findings proved that MARCH8 blocks gB cleavage by recruiting furin but this activity does not inhibit viral infection in vitro. Furthermore, we confirmed that MARCH8 inhibits cell-to-cell fusion independent of its E3 ubiquitin ligase activity but dependent on the interaction with the cell-to-cell fusion complex (gB, gD, gH, and gL). Finally, we discovered that the distribution of the cell-to-cell fusion complex is significantly altered and trapped within the trans-Golgi network. Overall, our results indicate that human MARCH8 acts as a potent antiviral host factor against PRV via trapping the cell-to-cell fusion complex in the trans-Golgi network.

Chiral phosphoric acid-catalyzed asymmetric epoxidation of alkenyl aza-heteroarenes using hydrogen peroxide.

The synthesis of chiral α-azaheteroaryl oxiranes via enantioselective catalysis is a formidable challenge due to the required complex stereoselectivity and diverse N-heterocyclic structures. These compounds play a crucial role in developing bioactive molecules, where precise chirality significantly influences biological activity. Here we show that using chiral phosphoric acid as a catalyst, our method efficiently addresses these challenges. This technique not only achieves high enantio- and diastereoselectivity but also demonstrates superior chemo- and stereocontrol during the epoxidation of alkenyl aza-heteroarenes. Our approach leverages a synergistic blend of electrostatic and hydrogen-bonding interactions, enabling the effective activation of both substrates and hydrogen peroxide. The resulting chiral oxiranes exhibit enhanced diversity and functionality, aiding the construction of complex chiral azaaryl compounds with contiguous stereocenters. Kinetic and density functional theory studies elucidate the mechanism, highlighting chiral phosphoric acid's pivotal role in this intricate enantioselective process.

A new 3,4-dinorsteroid from the marine sponge Cliona sp.

A new steroid, 2a-oxa-2-oxo-5ß-hydroxy-3,4-dinor-24-methylcholesta-22E-ene (1), together with 10 known ones (2-11), was isolated from the marine sponge Cliona sp. The structures of these compounds were determined by the spectroscopic methods (UV, IR, MS, and NMR) and X-ray diffraction analysis. Compound 1 was the third example of 3,4-dinorsteroid with a hemiketal at C-5 that was isolated from the natural source. In addition, the antibacterial activities of these compounds were also evaluated. However, none of them exhibited significant inhibition effects.

MARCH1 and MARCH2 inhibit pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in trans-Golgi network.

The membrane-associated RING-CH (MARCH) family of proteins are members of the E3 ubiquitin ligase family and are essential for a variety of biological functions. Currently, MARCH proteins are discovered to execute antiviral functions by directly triggering viral protein degradation or blocking the furin cleavage of viral class I fusion proteins. Here, we report a novel antiviral mechanism of MARCH1 and MARCH2 (MARCH1/2) in the replication of Pseudorabies virus (PRV), a member of the Herpesviridae family. We discovered MARCH1/2 restrict PRV replication at the cell-to-cell fusion step. Furthermore, MARCH1/2 block gB cleavage, and this is dependent on their E3 ligase activity. Interestingly, the blocking of gB cleavage by MARCH1/2 does not contribute to their antiviral activity in vitro. We discovered that MARCH1/2 are associated with the cell-to-cell fusion complex of gB, gD, gH, and gL and trap these viral proteins in the trans-Golgi network (TGN) rather than degrading them. Overall, we conclude that MARCH1/2 inhibit PRV by trapping the viral cell-to-cell fusion complex in TGN.

Single-Cell Transcriptome Landscape and Cell Fate Decoding in Human Brain Organoids after Transplantation.

Human stem cells and derivatives transplantation are widely used to treat nervous system diseases, while the fate determination of transplanted cells is not well elucidated. To explore cell fate changes of human brain organoids before and after transplantation, human brain organoids are transplanted into prefrontal cortex (PFC) and hippocampus (HIP), respectively. Single-cell sequencing is then performed. According to time-series sample comparison, transplanted cells mainly undergo neural development at 2 months post-transplantation (MPT) and then glial development at 4MPT, respectively. A different brain region sample comparison shows that organoids grafted to PFC have obtained cell fate close to those of host cells in PFC, other than HIP, which may be regulated by the abundant expression of dopamine (DA) and acetylcholine (Ach) in PFC. Meanwhile, morphological complexity of human astrocyte grafts is greater in PFC than in HIP. DA and Ach both activate the calcium activity and increase morphological complexity of astrocytes in vitro. This study demonstrates that human brain organoids receive host niche factor regulation after transplantation, resulting in the alignment of grafted cell fate with implanted brain regions, which may contribute to a better understanding of cell transplantation and regenerative medicine.

Marcytoglobosins A and B, Cytochalasans From a Marine Sponge Associated Chaetomium globosum 162105 Fungus.

Two new cytochalasans, marcytoglobosins A (1) and B (2) were isolated from the marine sponge associated fungus Chaetomium globosum 162105, along with six known compounds (3-8). The complete structures of two new compounds were determined based on 1D/2D NMR and HR-MS spectroscopic analyses coupled with ECD calculations. All eight isolates were evaluated for their antibacterial activity. Among them, compounds 3-8 displayed antibacterial effects against Staphylococcus epidermidis, Bacillus thuringiensis, Pseudomonas syringae pv. Actinidiae, Vibrio alginolyticus, and Edwardsiella piscicida with minimum inhibitory concentration (MIC) values ranging from 10 to 25 µg/mL.

The circadian clock affects starvation resistance through the pentose phosphate pathway in silkworm, Bombyx mori.

Disruption of the circadian clock can affect starvation resistance, but the molecular mechanism is still unclear. Here, we found that starvation resistance was significantly reduced in the core gene BmPer deficient mutant silkworms (Per-/-), but the mutant's starvation resistance increased with larval age. Under natural physiological conditions, the weight of mutant 5th instar larvae was significantly increased compared to wild type, and the accumulation ability of triglycerides and glycogen in the fat bodies was upregulated. However, under starvation conditions, the weight consumption of mutant larvae was increased and cholesterol utilization was intensified. Transcriptome analysis showed that beta-oxidation was significantly upregulated under starvation conditions, fatty acid synthesis was inhibited, and the expression levels of genes related to mitochondrial function were significantly changed. Further investigations revealed that the redox balance, which is closely related to mitochondrial metabolism, was altered in the fat bodies, the antioxidant level was increased, and the pentose phosphate pathway, the source of reducing power in cells, was activated. Our findings suggest that one of the reasons for the increased energy burden observed in mutants is the need to maintain a more robust redox balance in metabolic tissues. This necessitates the diversion of more glucose into the pentose phosphate pathway to ensure an adequate supply of reducing power.

The exploration of a compound cone-beam CT contrast agent for diagnosis of human extracted cracked tooth.

Objectives: This study aims to investigate the use of sodium iodide (NaI), dimethyl sulfoxide (DMSO), ethyl alcohol, and ethyl acetate as cone-beam CT (CBCT) contrast agents for diagnosing cracked teeth. The optimal delay time for detecting the number of crack lines beyond the dentino-enamel junction (Nd), the number of cracks extending from the occlusal surface to the pulp cavity (Np), and the depth of the crack lines was explored. Methods: 14 human extracted cracked teeth were collected, 12 were used for enhanced scanning, and 2 were used for exploring the characteristic of crack lines. The teeth were scanned in 3 CBCT enhanced scanning (ES) modes: ES1 using meglumine diatrizoate (MD); ES2 using NaI and DMSO, ES3 using NaI, DMSO, ethyl alcohol and ethyl acetate. Three delay times (15mins, 30mins, and 60mins) were set for scanning. Nd, Np, and depth of crack lines were evaluated. Results: There were totally 24 crack lines on 12 cracked teeth. Nd was 10 in ES1 at 60mins, 24 in ES2 at 60mins and 24 in ES3 at 15mins. Np was 1 in ES1 at 60mins, 10 in ES2 at 60mins and 21 in ES3 at 60mins, and there were significantly different among them (p < 0.01). The average depth presented on ES3 was significantly deeper than ES1 and ES2 (p < 0.01). Conclusion: NaI, DMSO, ethyl alcohol and ethyl acetate show potential as contrast agents for enhanced CBCT scanning in diagnosis of cracked teeth and their depth in vivo. A delay time of 15 min is necessary to confirm the existence of crack lines, while a longer delay time is required to ascertain if these crack lines extend to the pulp cavity.

Successful Treatment of Severe Case of Lipid Overload Syndrome with Pancreatitis and Pneumonia: A Case Report.

Background: Fat overload syndrome is a rare and severe adverse reaction triggered by the infusion of a single source of lipid emulsion, resulting in elevated blood triacylglycerol (TG) levels. The majority of literature reports focus on cases of fat overload syndrome in patients with mild symptoms. This case is significant because it demonstrates the diagnostic and therapeutic experience and provide valuable insights for the management for severe fat overload syndrome. Case Presentation: We present a case report of a female patient who developed fat overload syndrome following prolonged and excessive infusion of lipid emulsion after colon resection surgery. In the setting of compromised immune function and malnutrition, the patient's pulmonary infection and respiratory distress symptoms have further exacerbated. Hence, in addition to severe pancreatitis, the patient has also contracted severe pneumonia. Upon admission, tracheal intubation, plasma exchange and blood perfusion were performed. Subsequently, comprehensive treatment was provided, including anti-infection, antispasmodic, acid suppression, enzyme inhibition, as well as targeted supportive measures to stabilize electrolytes and nutritional status. After treatment, there was a progressive reduction in blood lipid levels. After assessing the relevant risks, it was deemed necessary to perform an emergency computed tomography (CT)-guided percutaneous drainage tube placement procedure targeting the necrotic area of the pancreas while the patient was still intubated. Finally, the patient was discharged from the hospital. Conclusion: The case highlights the association between fat overload syndrome and pancreatitis as well as the use of lipid emulsions and suggests the treatment strategies for severe fat overload syndrome.

Two new withanolides from Physalis minima L.

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

Geminal-dithiol-based precursors for reactive sulfur species.

Caged gem-dithiols have been developed as the donors of reactive sulfur species (RSS), but the chemistry of free gem-dithiols as RSS donors has not been well understood. Herein, we report the study of a free gem-dithiol, 1,3-diphenylpropane-2,2-dithiol, as the precursor for several RSS. It releases H2S under physiological conditions and can be converted to a mono-S-nitrosothiol, which serves as a NO donor. Furthermore, it can be converted to 3,3-dibenzyldithiirane, which is an active sulfur transfer reagent and can induce S-persulfidation.