Owing to the wide and growing demand for primary alcohols, the development of efficient catalysts with high regioselectivity remains a worthwhile pursuit. However, according to Markovnikov's rule, it ...is a challenge to obtain primary alcohols with high yields and regioselectivity from terminal alkenes or alkynes. Herein, we report the synthesis of a photosensitizing two‐dimensional (2D) metal–organic framework (MOF) from cyclic trinuclear copper(I) units (Cu‐CTUs) and a boron dipyrro‐methene (Bodipy) ligand. The MOF features broadband light absorption, excellent photoinduced charge separation efficiency, and photochemical properties. By integrating the copper‐catalyzed hydroboration and photocatalyzed aerobic oxidation, it can catalyze terminal alkenes and alkynes to produce primary alcohols via a one‐pot tandem reaction with excellent regioselectivity, good overall yields in two‐step reactions (up to 85 %), broad substrate compatibility (32 examples) and good reusability under mild conditions.
A Cu‐CTU‐based photosensitizing covalent metal–organic framework (JNM‐20) was constructed. The MOF possessed broadband light absorption, excellent photoinduced charge‐separation efficiency, and photochemical properties, allowing the production of primary alcohols from terminal alkenes and alkynes with excellent anti‐Markovnikov selectivity, good overall yields, broad substrate compatibility, and good reusability via tandem catalysis.
lKetamine functioned as a prophylactic agent against postpartum depression.lKetamine relieved suicidal ideation in women with postpartum depression.lThe antidepressant efficacy of ketamine was more ...obvious in some subgroups. (e.g., women with antenatal depressive symptom and antenatal suicidal ideation).
This study aimed to explore the effect of prophylactic ketamine administration on postpartum depression in Chinese woman undergoing cesarean section. This randomized controlled study included 654 Chinese women undergoing cesarean section. At 10 min after child birth, patients in the ketamine group were given 0.5 mg/kg ketamine, whereas patients in the control group received standard postpartum care. At the end of operation, all patients were armed with a patient-controlled intravenous analgesia device. The primary outcome was the prevalence of postpartum depression (PPD), as assessed by the Edinburgh Postnatal Depression Scale (EPDS), and the secondary outcomes included the safety assessment and the Numerical Rating Scale (NRS) of postoperative pain. The prevalence of postpartum blues and postpartum depression were significantly lower in the ketamine group than in the control group. Logistic analysis showed that ketamine administration protected against postpartum depression, and PPD-associated risk factors included stress during pregnancy, antenatal depressive symptom and antenatal suicidal ideation. In addition, the antidepressive effect of prophylactic ketamine was stronger in mothers with a history of moderate stress during pregnancy, antenatal depressive symptom and antenatal suicidal ideation. Our findings suggest that ketamine functions as a prophylactic agent against PPD.
Allylic amines are versatile building blocks in organic synthesis and exist in bioactive compounds, but their synthesis via hydroaminoalkylation of alkynes with amines has been a formidable ...challenge. Here, we report a late transition metal Ni-catalyzed hydroaminoalkylation of alkynes with N-sulfonyl amines, providing a series of allylic amines in up to 94% yield. Double ligands of N-heterocyclic carbene (IPr) and tricyclohexylphosphine (PCy
) effectively promote the reaction.
Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data ...analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
Most patients with triple negative breast cancer (TNBC) do not respond to anti-PD1/PDL1 immunotherapy, indicating the necessity to explore immune checkpoint targets. B7H3 is a highly glycosylated ...protein. However, the mechanisms of B7H3 glycosylation regulation and whether the sugar moiety contributes to immunosuppression are unclear. Here, we identify aberrant B7H3 glycosylation and show that N-glycosylation of B7H3 at NXT motif sites is responsible for its protein stability and immunosuppression in TNBC tumors. The fucosyltransferase FUT8 catalyzes B7H3 core fucosylation at N-glycans to maintain its high expression. Knockdown of FUT8 rescues glycosylated B7H3-mediated immunosuppressive function in TNBC cells. Abnormal B7H3 glycosylation mediated by FUT8 overexpression can be physiologically important and clinically relevant in patients with TNBC. Notably, the combination of core fucosylation inhibitor 2F-Fuc and anti-PDL1 results in enhanced therapeutic efficacy in B7H3-positive TNBC tumors. These findings suggest that targeting the FUT8-B7H3 axis might be a promising strategy for improving anti-tumor immune responses in patients with TNBC.
Abstract
BACKGROUND:
Improved understanding of rod fracture (RF) in adult spinal deformity could be valuable for implant design, surgical planning, and patient counseling.
OBJECTIVE:
To evaluate ...symptomatic RF after posterior instrumented fusion for adult spinal deformity.
METHODS:
A multicenter, retrospective review of RF in adult spinal deformity was performed. Inclusion criteria were spinal deformity, age older than 18 years, and more than 5 levels posterior instrumented fusion. Rod failures were divided into early (⩽12 months) and late (>12 months).
RESULTS:
Of 442 patients, 6.8% had symptomatic RF. RF rates were 8.6% for titanium alloy, 7.4% for stainless steel, and 2.7% for cobalt chromium. RF incidence after pedicle subtraction osteotomy (PSO) was 15.8%. Among patients with a PSO and RF, 89% had RF at or adjacent to the PSO. Mean time to early RF (63%) was 6.4 months (range, 2-12 months). Mean time to late RF (37%) was 31.8 months (range, 14-73 months). The majority of RFs after PSO (71%) were early (mean, 10 months). Among RF cases, mean sagittal vertical axis improved from preoperative (163 mm) to postoperative (76.9 mm) measures (P < .001); however, 16 had postoperative malalignment (sagittal vertical axis >50 mm; mean, 109 mm).
CONCLUSION:
Symptomatic RF occurred in 6.8% of adult spinal deformity cases and in 15.8% of PSO patients. The rate of RF was lower with cobalt chromium than with titanium alloy or stainless steel. Early failure was most common after PSO and favored the PSO site, suggesting that RF may be caused by stress at the PSO site. Postoperative sagittal malalignment may increase the risk of RF.
The synthesis of atomically precise copper nanoclusters (Cu‐NCs) with high chemical stability is a prerequisite for practical applications, yet still remains a long‐standing challenge. Herein, we ...have prepared a pyrazolate‐protected Cu‐NC (Cu8), which exhibited exceptional chemical stability either in solid‐state or in solution. The crystals of Cu8 are still suitable for single crystal X‐ray diffraction analysis even after being treated with boiling water, 8 wt % H2O2, high concentrated acid (1 M HCl) or saturated base (≈20 M KOH), respectively. More importantly, the structure of Cu8 in solution also remained intact toward oxygen, organic acid (100 eq. HOAc) or base (400 eq. dibutylamine) confirmed by 1H NMR and UV/Vis analysis. Taking advantage of high alkali‐resistant, Cu8 illustrates excellent catalytic activity for the synthesis of indolizines, and it can be reused for at least 10 cycles without losing catalytic performance.
An atomically precise pyrazolate‐protected copper nanocluster exhibits extraordinary chemical stability toward oxygen, heat, oxidant (8 wt % H2O2), acid (1 M HCl) and base (20 M KOH). It has been used as stable homogeneous catalysts for synthesis of indolizine with exceptional catalytic activity, delivering superior TOF (3380 h−1) compared to other reported catalysts.
Antibody (Ab)‐based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of ...target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab‐based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag‐X (S‐X) to form the SpaCC‐S‐X complex, which binds non‐covalently to an Ab to form the Ab‐SpaCC‐S‐X protein complex. The “X” can be a variety of small molecules such as fluoresceins, cell‐penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab‐SpaCC‐S‐FITC(−TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab‐SpaCC‐SN3‐MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab‐DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab‐SpaCC‐SN3‐Ap boosted the tumor‐killing function of T‐cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy.
The medial prefrontal cortex (mPFC) is essential for social behaviors, yet whether and how it encodes social memory remains unclear.
We combined whole-cell patch recording, morphological analysis, ...optogenetic/chemogenetic manipulation, and the TRAP (targeted recombination in active populations) transgenic mouse tool to study the social-associated neural populations in the mPFC.
Fos-TRAPed prefrontal social-associated neurons are excitatory pyramidal neurons with relatively small soma sizes and thin-tufted apical dendrite. These cells exhibit intrinsic firing features of dopamine D1 receptor–like neurons, show persisting firing pattern after social investigation, and project dense axons to nucleus accumbens. In behaving TRAP mice, selective inhibition of prefrontal social-associated neurons does not affect social investigation but does impair subsequent social recognition, whereas optogenetic reactivation of their projections to the nucleus accumbens enables recall of a previously encountered but “forgotten” mouse. Moreover, chemogenetic activation of mPFC-to-nucleus accumbens projections ameliorates MK-801–induced social memory impairments.
Our results characterize the electrophysiological and morphological features of social-associated neurons in the mPFC and indicate that these Fos-labeled, social-activated prefrontal neurons are necessary and sufficient for social memory.
In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor‐associated regulatory factors. LncRNA growth arrest‐specific transcript 5 (Gas5) acts as an anti‐oncogene ...in most cancers. Whether Gas5 acts as an oncogene or anti‐oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription‐polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull‐down experiments and analyzed by mass spectrometry. A series of novel Gas5‐interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose‐regulated protein (GRP78) was identified as a direct target of Gas5 by Rip‐qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5‐mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.
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