Palladium-Catalyzed Cascade Reaction in Water to Imidazo[1,2-a]pyridazines as Switchable DSEgens, AIEgens, and ACQgens.

Dual-state emission (DSE) luminophores exhibit strong emissions in both solution and solid states, filling the gaps between aggregation-induced emissions (AIE) and aggregation-caused quenching (ACQ). However, limited design concepts and complicated synthetic strategies restrict the discovery of novel DSE molecules. Developing efficient and green methodologies to access novel DSE scaffolds via rational design remains highly desirable. In this work, we report a water-promoted Pd-catalyzed cascade reaction for the synthesis of multi-substituted imidazo[1,2-a]pyridazine derivatives with DSE properties. The intramolecular interactions of the neighboring benzene rings restrict molecular motion, leading to emissions in the solid state (quantum yield: 11 %), and the newly constructed core structure of imidazo[1,2-a]pyridazine ensures considerable planarity, allowing for emissions in solution. Further removal of the neighboring phenyl groups resulted in ACQgens, while additional methyl groups led to AIEgens. Subsequent live cell imaging investigations suggested that the novel DSEgens could serve as specific lipid droplet (LD) probes in a wide concentration range.

Room-Temperature Phosphorescence in Pure Organic Materials: Halogen Bonding Switching Effects.

Organic room-temperature phosphorescence (ORTP), when combined with external stimuli-responsive capability, is very attractive for sensors and bio-imaging devices, but remains challenging. Herein, by doping two ß-iminoenamine-BF2 derivatives (S-2CN and S-2I) into a 4-iodoaniline (I-Ph-NH2 ) crystalline matrix, the formation of S-2CN⋅⋅⋅I-Ph-NH2 and S-2I⋅⋅⋅I-Ph-NH2 halogen bonds leads to bright-red RTP emissions from these two host-guest doped crystals (hgDCs) with quantum efficiencies up to 13.43 % and 15.96 %, respectively. Upon treatment with HCl, the competition of I-Ph-NH2 ⋅HCl formation against S-2I⋅⋅⋅I-Ph-NH2 halogen bonding switches off the red RTP from S-2I/I-Ph-NH2 hgDCs, whereas the stable halogen-bonded S-2CN⋅⋅⋅I-Ph-NH2 ensures red RTP from S-2CN/I-Ph-NH2 hgDCs remains unchanged. A security protection luminescence pattern by using these different HCl-responsive RTP behaviors was designed.

Intravenous lidocaine suppresses dexamethasone-induced perineal pruritus during anesthesia induction: a randomized controlled, double blind study.

Previous studies have found that intravenous dexamethasone may produce perineal pruritus in some patients when administered as premedicant in the preoperative period. This randomized controlled, double-blind study evaluated the efficacy of pretreatment of lidocaine on the incidence and severity of dexamethasone-induced perineal pruritus. 400 patients were enrolled in this study and allocated randomly into four groups (n=100, in each). Then, patients received intravenously anesthesia induction as the following sequence of medications: injecting 0.9% sodium chloride (placebo) 10 mL in group I, lidocaine 0.5mg/kg in group II, lidocaine 1mg/kg in group III, and lidocaine 1.5mg/kg in group IV, 1 minute later, injecting 10mg dexamethasone in all groups. The severity of perineal pruritus was graded based on the VAS as none (VAS 0), mild (VAS 1-3), moderate (4-6), or severe (VAS 7 to 10), and recorded the occurrence, the severity and the duration of perineal pruritus. Occurrence of perineal pruritus was significantly reduced in group III and group IV (8%, 9% vs 40% and 33% in Groups I and II, respectively, p<0.05). The incidence of perineal pruritus of females was higher than males in groups I and II (P<0.05). The duration of perineal pruritus was shorter in group IV compared to groups I, II and III (p<0.05). We conclude that pretreatment 1mg/kg or 1.5mg/kg lidocaine may effectively reduce the incidence of perineal pruritus.

[Experimental study on Dendrobium candidum polysaccharides on promotion of hair growth].

OBJECTIVE: To observe the effect and mechanism of Dendrobium candidum polysaccharides (DCP) in promoting hair growth, in order to lay a foundation for the development and utilization of D. candidum. METHOD: The water-extraction and alcohol-precipitation method was adopted to extract DCP, and the phenol-sulphuric acid method was used to determine its content. Thirty C57BL6J mice were collected to establish the hair loss model with hair removal cream. They were randomly divided into the control group, the positive control group and the DCP group, and given 0.2 mL of ultra-pure water, minoxidil tincture and DCP (5.0 g x L(-1)) 21 days. The mice hair growth scoring standard was adopted to evaluate the hair growth of C57BL/6J mice at 7, 14 d. The hairs in unit hair-losing areas of treated C57BL/6J mice at 21 d were weighed to evaluate the effect of DCP on the promotion of hair growth. MTT assay and RT-PCR method were used to evaluate the effect of DCP on the proliferatin of HaCaT cells and the mRNA expression of VEGF in HaCaT cells. RESULT: The extraction percent of DCP was 29.87%, and its content was 79.65%. The average scores for the hair growth and weight of C57BL/6J mice of DCP group were much higher than the control group. The survival rate and mRNA expression of VEGF of HaCaT cells were much higher than the control group. CONCLUSION: DCP has the effect in promoting hair growth. Its mechanism may be related to the up-regulation of the mRNA expression of VEGF.

Efficacy and safety of neuromodulation for apathy in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Non-pharmacological interventions, including noninvasive neuromodulation, may alleviate apathy in individuals with Alzheimer's disease. This systematic review and meta-analysis investigated the efficacy and safety of neuromodulation for apathy in elderly patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). METHODS: The Cochrane Central Register of Controlled Trials, EMBASE, and PubMed databases were searched for randomized controlled trials (RCTs) of neuromodulation for apathy in AD or MCI. The primary outcome was change in apathy based on the Apathy Evaluation Scale. Secondary outcomes were change in global cognition and trial discontinuation. RESULTS: The meta-analysis included four RCTs involving 89 patients (aged 65.6-80.5 years) with apathy in AD or MCI. Findings showed no significant improvement in apathy (SMD = 0.57, 95% CI = -0.22-1.36; P = 0.16) or global cognition (SMD = 0.83, 95% CI = -0.11-1.78; P = 0.08) with neuromodulation compared to sham. Subgroup analyses showed significant improvement in apathy with high-frequency rTMS at 120% RMT compared to sham (SMD = 1.36, [95% CI = 0.61-2.12]; P = 0.0004), but not with rTMS at 80% RMT. For global cognition, high-frequency rTMS resulted in significant enhancement (SMD = 1.34 [95% CI = 0.59-2.10]; P = 0.0005), but no notable difference was observed with tDCS compared to sham. There was no significant difference in trial discontinuation in patients with AD or MCI treated with neuromodulation compared to sham. CONCLUSION: High-frequency rTMS at 120% RMT for four weeks may be efficacious and safe for the treatment of apathy in elderly patients with AD or MCI. High-frequency rTMS may also improve global cognition in these patients. This implies rTMS has potential as an intervention for apathy in AD and MCI. Large well conducted RCTs are warranted to explore this effect further.

Research on improved YOLOV7-SSWD digital meter reading recognition algorithms.

Meter reading recognition is an important link for robots to complete inspection tasks. To solve the problems of low detection accuracy and inaccurate localization of current meter reading recognition algorithms, the YOLOV7-SSWD (YOLOV7-SiLU-SimAM-Wise-IoU-DyHeads) model is proposed, a novel detection model based on the multi-head attention mechanism, which is improved on the YOLOV7-Tiny model. First, the Wise-IoU loss function is used to solve the problem of sample quality imbalance and improve the model's detection accuracy. Second, a new convolutional block is constructed using the SiLU activation function and applied to the YOLOV7-Tiny model to enhance the model's generalization ability. The dynamic detection header is then built as the header of YOLOV7-Tiny, which realizes the fusion of multi-scale feature information and improves the target recognition performance. Finally, we introduce SimAM to improve the feature extraction capability of the network. In this paper, the importance of each component is fully verified by ablation experiments and comparative analysis. The experiments showed that the mAP and F1-scores of the YOLOV7-SSWD model reached 89.8% and 0.84. Compared with the original network, the mAP increased by 8.1% and the F1-scores increased by 0.1. The YOLOV7-SSWD algorithm has better localization and recognition accuracy and provides a reference for deploying inspection robots to perform automatic inspections.

Research progress of robot and laparoscope in postoperative complications of rectal cancer.

Rectal cancer is one of the most common malignant tumours worldwide, and it is also one of the major diseases that seriously threatens human life and health. At present, the main treatment for rectal cancer is still surgical treatment. The surgical methods have been rapidly developed from the previous open surgery to the current minimally invasive surgery. At present, there are two main minimally invasive surgeries: robotic surgery and laparoscopic surgery. Due to the particularity of rectal cancer surgery, more and more studies have shown that robotic rectal cancer surgery has more advantages than laparoscopic rectal cancer surgery. However, whether the incidence of postoperative complications after robotic rectal cancer surgery is lower than that after laparoscopy is not uniformly conclusive in the current study. Therefore, in this paper, we searched Pubmed, Cochrane Library, Embase and other databases, collected the latest published meta-analysis on postoperative complications of robots and laparoscopy in rectal cancer, and assessed the quality of the included meta-analysis by AMSTAR-2 evaluation tool, so as to explore the current research status and research quality of postoperative complications of robots and laparoscopy in rectal cancer. The results showed that compared with laparoscopic rectal cancer surgery, robotic rectal cancer surgery could improve the postoperative urinary and reproductive function of male patients, but it could not be proved that robotic rectal cancer surgery could reduce the incidence of postoperative complications, anastomotic leakage, urinary retention, intestinal obstruction, anastomotic bleeding, incision infection, pulmonary infection, venous thrombosis and abdominal abscess; however, the overall quality of meta-analysis of the results of each complication was low or very low. Therefore, multicenter, large-sample, high-quality prospective randomised controlled studies and high-quality meta-analysis are still needed to prove the advantages of robotic rectal cancer surgery in postoperative complications in the future.

Organ donation after brain death from autoimmune glial fibrillary acidic protein astrocytopathy: A case report.

Background: No reports of organ donation have been documented in patients suffering from severe autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Case presentation: A 27-year-old male patient developed a fever and headache, followed a week later by weakness and unsteadiness in his limbs. He attended his local hospital, but no cause was found. Thirteen days later, he became unconscious and was promptly moved to the intensive care unit for symptomatic support treatment, with no improvement. He was then transferred to our hospital, where he suffered a cardiac arrest on the same day. The family abandoned treatment and opted for organ donation, for financial reasons. Cell-based assays demonstrated GFAP antibodies in the cerebrospinal fluid. Two kidney recipients and one liver recipient showed no abnormal reactions 15 months after receiving organ transplants. Conclusions: We report a case of organ donation following brain death in a patient diagnosed with GFAP astrocytopathy, highlighting the need for vigilance regarding the potential occurrence of cardiac arrest in patients with this condition. Considering the potential of GFAP astrocytopathy is crucial when observing deteriorating symptoms, seizures, and consciousness disturbances subsequent to a suspected viral infection. Successful organ donation from patients with GFAP astrocytopathy may be feasible given the exclusion of systemic infection and the absence of peripheral organ involvement.

Distillers' grains organic fertilizer alters soil bacterial composition and co-occurrence patterns in a tobacco-growing field.

In recent years, numerous studies have indicated that the combination of organic and inorganic fertilizers can effectively improve soil fertility and soil productivity. Distillers' grain (DG), the primary by-product of Chinese spirits production, has a high utilization value for producing organic fertilizer. We investigated the effects of distillers' grain organic fertilizer (DGOF) on soil chemical properties and microbial community composition, as well as the effects of chemical properties on the abundance of keystone species. The results indicated that the application of DGOF significantly increased tobacco yield by 14.8% and mainly affected the composition rather than the alpha diversity of the bacterial community. Ten amplicon sequence variants (ASVs) were identified as keystone species in the bacterial communities, and most of their relative abundance was influenced by the DGOF addition through affecting soil chemical properties. Our results elucidated the alterations in soil chemical properties and microbial community composition resulting from DGOF application, which is of great importance to better understand the relationship between DGOF and soil microorganisms in the flue-cured tobacco cultivation field.

Discontinuity of deep medullary veins in SWI is associated with deep white matter hyperintensity volume and cognitive impairment in cerebral small vessel disease.

BACKGROUND: Discontinuation of the deep medullary veins (DMVs) may be an early imaging marker for identifying cognitive impairment caused by cerebral small vessel disease (CSVD). However, this method lacks mechanistic exploration. We aimed to investigate whether the DMV score is related to CSVD imaging markers and cognitive impairment in patients with CSVD. METHODS: This retrospective study included patients with CSVD who completed DMV score and cognition (e.g., MMSE, MoCA) assessments, and underwent MRI scanning (T2-FLAIR for white matter hyperintensities (WMH) volume, T1-weighted MRI for brain parenchymal fractions (BPF) analysis, and SWI for assessment of DMV score). The CSVD imaging markers were quantitatively assessed using the AccuBrain® system. We assessed the diagnostic value of neuroimaging biomarkers for detecting CSVD-related cognitive impairment. In addition, we explored the relationship between the DMV score, CSVD imaging markers, and cognition using mediation analysis. RESULTS: Ninety-four patients with CSVD were divided into a cognitive impairment group (n = 39) and a non-cognitive impairment group (n = 55). Higher DMV scores, larger WMH volumes, and smaller BPF were observed in the cognitive impairment group than those in the non-cognitive impairment group. Receiver operating characteristics (ROC) analysis revealed that the discovery value of the integration of patient age, BPF, whole WMH volume, and DMV score for cognitive impairment was 0.742, with a sensitivity and specificity of 79.5 % and 61.5 %, respectively. Mediation analysis showed mediation by WMH and BPF in the relationship between DMV score and cognitive impairment (all P < 0.05). LIMITATIONS: This study did not evaluate the DMV score in subregions according to DMV anatomy. CONCLUSIONS: The DMV score is significantly associated with cognitive impairment in patients with CSVD, and this association is mediated through WMH and BPF.

Lower serum uric acid and impairment of right cerebral hemisphere structural brain networks are related to depressive symptoms in cerebral small vessel disease: A cross-sectional study.

Cerebral small vessel disease (SVD) may be associated with an increased risk of depressive symptoms. Serum uric acid (SUA), an antioxidant, may be involved in the occurrence and development of depressive symptoms, but the mechanism remains unknown. Moreover, the relationship between structural brain networks and SUA has not been explored. This study examined the relationship between SUA and depressive symptoms in patients with SVD using graph theory analysis. We recruited 208 SVD inpatients and collected fasting blood samples upon admission. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). Magnetic resonance imaging was used to evaluate SVD, and diffusion tensor images were used to analyze structural brain networks using graph theory. Patients with depressive symptoms (n = 34, 25.76%) compared to those without (334.53 vs 381.28 µmol/L, p = 0.017) had lower SUA levels. Graph theoretical analyses showed a positive association of SUA with betweenness centrality, nodal efficiency, and clustering coefficients and a negative correlation with the shortest path length in SVD with depressive symptoms group. HAMD scores were significantly associated with nodal network metrics in the right cerebral hemisphere. Our findings suggested that lower SUA levels are significantly associated with disrupted structural brain networks in the right cerebral hemisphere of patients with SVD who have depressive symptoms.

Aza-dicyclopenta[a,g]naphthalenes: controllable seesaw-like emissive behavior and narrowband AIEgens.

Molecular motions significantly influence the emissive behavior and properties of organic fluorescent molecules. However, achieving controllable emission remains a major challenge for fluorophores. In the case of aggregation-induced emission luminogens (AIEgens), the desired properties of aggregated emission and narrowband spectrum demand molecular motion patterns that inherently oppose each other. A nitrogen-containing dicyclopenta[a,g]naphthalene scaffold was discovered as a controllable luminogenic structure through a highly efficient one-step intermolecular cascade reaction. By carefully balancing molecular motions and introducing additional nitrogen atoms into the skeleton, pyrrole-conjugated dicyclopenta[a,g]naphthalenes with aggregation-caused quenching (ACQ) could be transformed into dual-state emission luminogens (DSEgens). This transformation was achieved by incorporating an additional weak H-bond "lock." Furthermore, the DSEgens could be converted into AIEgens with an exciting narrow full-width-at-half-maximum (FWHM, <50 nm) by methylation. This unprecedented discovery is attributed to the contribution of the weak H-bond "lock," which overcomes the limitations of broad band emission in AIEgens caused by restrictions of intramolecular motion. Specific organelle probes were developed by replacing the methyl group of the onium product with different positioning groups. This study emphasizes the delicate balance of molecular motions in controlling luminescence and demonstrates a successful approach to designing organic luminogens with controllable emission and narrowband AIEgens.

Multi-scale detection of pulmonary nodules by integrating attention mechanism.

The detection of pulmonary nodules has a low accuracy due to the various shapes and sizes of pulmonary nodules. In this paper, a multi-scale detection network for pulmonary nodules based on the attention mechanism is proposed to accurately predict pulmonary nodules. During data processing, the pseudo-color processing strategy is designed to enhance the gray image and introduce more contextual semantic information. In the feature extraction network section, this paper designs a basic module of ResSCBlock integrating attention mechanism for feature extraction. At the same time, the feature pyramid structure is used for feature fusion in the network, and the problem of the detection of small-size nodules which are easily lost is solved by multi-scale prediction method. The proposed method is tested on the LUNA16 data set, with an 83% mAP value. Compared with other detection networks, the proposed method achieves an improvement in detecting pulmonary nodules.

Optimal parameter determination of repetitive transcranial magnetic stimulation for treating treatment-resistant depression: A network meta-analysis of randomized controlled trials.

Background: Many studies have shown the efficacy of repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD). However, the choice of different parameters has been a challenging issue. Methods: PubMed, Cochrane, and Embase databases were searched for relevant studies until June 20, 2022. The treatment efficacy was evaluated by the relative risk (RR) using the pairwise test for response and remission rates. Subgroup and sensitivity analyses were conducted to explore the primary outcome differences and to assess the reliability of the results. Results: Thirty-seven trials comprising 2120 participants with TRD were included. The more efficacious interventions compared to sham controls included high-frequency left followed by low-frequency right sup-threshold (HFL-LFR-sup-rTMS, RR = 5.29, 95% CI: 1.24-22.50), high-frequency left sup-threshold (HFL-sup-rTMS, RR = 2.97, 95% CI: 1.74-5.05), low-frequency right sup-threshold (LFR-sup-rTMS, RR = 2.72, 95% CI: 1.50-4.90), low-frequency right followed by high-frequency left sup-threshold (LFR-HFL-sup-rTMS, RR = 2.71, 95% CI: 1.62-4.53), and high-frequency left sub-threshold (HFL-sub-rTMS, RR = 1.91, 95% CI: 1.18-3.10) rTMS. The estimated relative ranking of treatments suggested that HFL-LFR-sup-rTMS (84.4%) might be the most efficacious among all rTMS strategies. No treatments showed a lower acceptability than the sham control. Limitations: Subgroup analysis was not conducted to compare the efficacy of rTMS treatment between bipolar and unipolar depression, and small-study effects possibly introduced bias. Conclusion: Treatment with HFL-LFR-sup-rTMS, HFL-sup-rTMS, LFR-sup-rTMS, LFR-HFL-sup-rTMS, or HFL-sub-rTMS is more efficacious than the sham control. HFL-LFR-sup-rTMS and HFL-sup-rTMS may be the two best among the most efficacious rTMS treatments. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42022334481].

Bacterial Community Composition and Function of Tropical River Ecosystem along the Nandu River on Hainan Island, China.

Microorganisms play a pivotal role in nutrient cycling in aquatic ecosystems. Understanding bacterial diversity and its functional composition are crucial for aquatic ecology and protection. We investigated the bacterial community structure using 16S rRNA gene amplicons high-throughput sequencing in this study. Results showed that 105 amplicon sequence variants (ASVs) account for 43.8% of the total sequences shared by the Nandu River's lower, middle, and upper reach and the Songtao Reservoir. The dominant bacterial phylum in the Nandu River and its connected Songtao Reservoir were Proteobacteria and Actinobacteriota, respectively. The highest Chao1 and Shannon index values were found in the lower reach of the Nandu River. Beta diversity analysis showed the divergence in bacterial communities in the Nandu River and Songtao Reservoir, but not in different reaches. Among the water properties, based on the Mantel test, dissolved oxygen, total nitrogen, and nitrite significantly affected the bacterial communities. The functional profiles predicted by Tax4Fun2 showed that metabolism was the most abundant function group. The relative abundance of genetic information processing was significantly higher in the Songtao Reservoir than in the Nandu River, while the relative abundance of human diseases was significantly lower in the Songtao Reservoir than in the Nandu River. The appearance of the xenobiotics biodegradation and metabolism function group requires us to pay more attention to possible water pollution, especially at the upper reach of the Nandu River.

A GRIP-1-EZH2 switch binding to GATA-4 is linked to the genesis of rhabdomyosarcoma through miR-29a.

Terminal differentiation failure is an important cause of rhabdomyosarcoma genesis, however, little is known about the epigenetic regulation of aberrant myogenic differentiation. Here, we show that GATA-4 recruits polycomb group proteins such as EZH2 to negatively regulate miR-29a in undifferentiated C2C12 myoblast cells, whereas recruitment of GRIP-1 to GATA-4 proteins displaces EZH2, resulting in the activation of miR-29a during myogenic differentiation of C2C12 cells. Moreover, in poorly differentiated rhabdomyosarcoma cells, EZH2 still binds to the miR-29a promoter with GATA-4 to mediate transcriptional repression of miR-29a. Interestingly, once re-differentiation of rhabdomyosarcoma cells toward skeletal muscle, EZH2 was dispelled from miR-29a promoter which is similar to that in myogenic differentiation of C2C12 cells. Eventually, this expression of miR-29a results in limited rhabdomyosarcoma cell proliferation and promotes myogenic differentiation. We thus establish that GATA-4 can function as a molecular switch in the up- and downregulation of miR-29a expression. We also demonstrate that GATA-4 acts as a tumor suppressor in rhabdomyosarcoma partly via miR-29a, which thus provides a potential therapeutic target for rhabdomyosarcoma.

Direct Transition-Metal Free Benzene C-H Functionalization by Intramolecular Non-Nitroarene Nucleophilic Aromatic Substitution of Hydrogen to Diverse AIEgens.

Direct C(sp2 )-H functionalization through nitroarene-triggered nucleophilic aromatic substitution of hydrogen (SNArH ) has attracted growing attention, owing to its high efficiency and low carbon footprint. In this study, non-nitro-group-assisted SN ArH has been developed for direct benzene functionalization in one pot under mild conditions. The electron-withdrawing carbonyl group and the halide or trifluoromethyl group on the phenyl ring enable the σH adduct formation to fulfill the intramolecular C(sp2 )-C(sp3 ) bond construction. Notably, the cyano group serves as both the electron-withdrawing group to activate the C(sp3 )-H bond and the leaving group to fulfill the ß-elimination. Three series of pyrrolo[1,2-b]isoquinolinones, as well as unexpected rearrangement products 3-(1H-pyrrol-2-yl)-1H-inden-1-ones are regioselectively obtained through a simple and efficient base-catalyzed one-pot strategy. Mechanistic studies indicate that the σH adduct from carbanion addition to hydrogen serves as the sole intermediate for all of the aforementioned transformations. These molecules show intense luminescence and the subsequent one-step structural modification results in the aggregation-induced emission (AIE) derivatives with redshifted full-color tunable fluorescence, large Stokes shifts, and good quantum yields. Further living cell imaging investigations suggest their potential application as specific bioprobes for lipid droplet localization and visualization.

Comparative efficacy and acceptability of neuromodulation procedures in the treatment of treatment-resistant depression: a network meta-analysis of randomized controlled trials.

BACKGROUND: Nearly half of the patients with depression experience suboptimal benefits from antidepressants. Neuromodulation therapies, a kind of technology that can regulate neuronal firing activity by electrical or magnetic stimulation, were introduced to improve this situation. However, the results from clinical trials have been inconsistent. METHODS: We followed the extension of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to perform this network meta-analysis (NMA). The results were evaluated by relative risk (RR) for the response, remission, and discontinuation rates. RESULTS: In total, 49 trials with 2,941 patients were included in this study. Bilateral theta burst stimulation (TBS, RR 5.00, 95% CI 1.11-22.44), priming transcranial magnetic stimulation (pTMS, RR 2.97, 95% CI 1.20-7.39), low-frequency right repetitive transcranial magnetic stimulation (TMS) (LFR-rTMS, RR 2.62, 95% CI 1.56-4.39), high-frequency left repetitive TMS (HFL-rTMS, RR 2.18, 95% CI 1.52-3.13), and bilateral repetitive TMS (BL-rTMS, RR 3.08, 95% CI 1.78-5.31) were demonstrated to have higher response rates than sham control. BL-rTMS (RR 3.12, 95% CI 1.06-9.09) was found to have a higher response rate than deep brain stimulation in this NMA. All measures had the non-inferiority acceptability than the sham-control. BL-rTMS was more acceptable than bitemporal ECT (BT-ECT, RR 0.18, 95% CI 0.03-0.89), while pTMS was more acceptable than BT-ECT (RR 0.08, 95% CI 0.01-0.55), HFL-rTMS (RR 0.34, 95% CI 0.12-0.93), and deep TMS (RR 0.15, 95% CI 0.02-0.96). CONCLUSION: Besides electroconvulsive therapy (ECT), rTMS, priming TMS, and bilateral TBS proved effective for patients with treatment-resistant depression (TRD). BL-rTMS showed high efficacy and acceptability, and bilateral TBS had the potential to be the most efficacious neuromodulation measures.

Privileged Biorenewable Secologanin-Based Diversity-Oriented Synthesis for Pseudo-Natural Alkaloids: Uncovering Novel Neuroprotective and Antimalarial Frameworks.

Bioprivileged molecules hold great promise for supplementing petrochemicals in sustainable organic synthesis of a diverse bioactive products library. Secologanin, a biorenewable monoterpenoid glucoside with unique structural elements, is the key precursor for thousands of natural monoterpenoid alkaloids. Inspired by its inherent highly congested functional groups, a secologanin-based diversity-oriented synthesis (DOS) strategy for novel pseudo-natural alkaloids was developed. All the reactive units of secologanin were involved in these operation simplicity protocols under mild reaction conditions, including the one-step enantioselective transformation of exocyclic C8, C8/C11, and C8/C9/C10 as well as the chemoenzymatic manipulation of endocyclic C2/C6 via the attack by various nucleophiles. A combinatory scenario of the aforementioned reactions further provided diverse polycyclic products with multiple chiral centers. Preliminary activity screening of these newly constructed molecules led to the discovery of antimalarial and highly potent neuroprotective skeletons. The application of green biorenewable secologanin in diversity-oriented pseudo-natural monoterpenoid alkaloid synthesis might encourage the pursuit of valuable bioactive frameworks.

Rhodium(iii)-catalyzed cascade reactions of benzoic acids with dioxazolones: discovery of 2,5-substituted benzoxazinones as AIE molecules.

A rhodium-catalyzed cascade reaction of benzoic acids with 1,4,2-dioxazol-5-ones was studied. The carboxyl group enabled a double C-H amidation followed by further intramolecular cyclization to afford 2,5-substituted benzoxazinones, which exhibited aggregation-induced emission (AIE) properties with a promising excited-state intramolecular proton-transfer (ESIPT) phenomenon.