SCREE: a comprehensive pipeline for single-cell multi-modal CRISPR screen data processing and analysis.

Single-cell CRISPR screens have been widely used to investigate gene regulatory circuits in diverse biological systems. The recent development of single-cell CRISPR screens has enabled multimodal profiling of perturbed cells with both gene expression, chromatin accessibility and protein levels. However, current methods cannot meet the analysis requirements of different types of data and have limited functions. Here, we introduce Single-cell CRISPR screens data analysEs and perturbation modEling (SCREE) as a comprehensive and flexible pipeline to facilitate the analyses of various types of single-cell CRISPR screens data. SCREE performs read alignment, sgRNA assignment, quality control, clustering and visualization, perturbation enrichment evaluation, perturbation efficiency modeling, gene regulatory score calculation and functional analyses of perturbations for single-cell CRISPR screens with both RNA, ATAC and multimodal readout. SCREE is available at https://github.com/wanglabtongji/SCREE.

Pulse pressure variation guided goal-direct fluid therapy decreases postoperative complications in elderly patients undergoing laparoscopic radical resection of colorectal cancer: a randomized controlled trial.

OBJECTIVE: The use of goal-directed fluid therapy (GDFT) has been shown to reduce complications and improve prognosis in high-risk abdominal surgery patients. However, the utilization of pulse pressure variation (PPV) guided GDFT in laparoscopic surgery remains a subject of debate. We hypothesized that utilizing PPV guidance for GDFT would optimize short-term prognosis in elderly patients undergoing laparoscopic radical resection for colorectal cancer compared to conventional fluid therapy. METHODS: Elderly patients undergoing laparoscopic radical resection of colorectal cancer were randomized to receive either PPV guided GDFT or conventional fluid therapy and explore whether PPV guided GDFT can optimize the short-term prognosis of elderly patients undergoing laparoscopic radical resection of colorectal cancer compared with conventional fluid therapy. RESULTS: The incidence of complications was significantly lower in the PPV group compared to the control group (32.8% vs. 57.1%, P = .009). Additionally, the PPV group had a lower occurrence of gastrointestinal dysfunction (19.0% vs. 39.3%, P = .017) and postoperative pneumonia (8.6% vs. 23.2%, P = .033) than the control group. CONCLUSION: Utilizing PPV as a monitoring index for GDFT can improve short-term prognosis in elderly patients undergoing laparoscopic radical resection of colorectal cancer. REGISTRATION NUMBER: ChiCTR2300067361; date of registration: January 5, 2023.

Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

STRIDE: accurately decomposing and integrating spatial transcriptomics using single-cell RNA sequencing.

The recent advances in spatial transcriptomics have brought unprecedented opportunities to understand the cellular heterogeneity in the spatial context. However, the current limitations of spatial technologies hamper the exploration of cellular localizations and interactions at single-cell level. Here, we present spatial transcriptomics deconvolution by topic modeling (STRIDE), a computational method to decompose cell types from spatial mixtures by leveraging topic profiles trained from single-cell transcriptomics. STRIDE accurately estimated the cell-type proportions and showed balanced specificity and sensitivity compared to existing methods. We demonstrated STRIDE's utility by applying it to different spatial platforms and biological systems. Deconvolution by STRIDE not only mapped rare cell types to spatial locations but also improved the identification of spatially localized genes and domains. Moreover, topics discovered by STRIDE were associated with cell-type-specific functions and could be further used to integrate successive sections and reconstruct the three-dimensional architecture of tissues. Taken together, STRIDE is a versatile and extensible tool for integrated analysis of spatial and single-cell transcriptomics and is publicly available at https://github.com/wanglabtongji/STRIDE.

Photocoupled Electroreduction of CO2 over Photosensitizer-Decorated Covalent Organic Frameworks.

Introducing an external visible-light field would be a promising strategy to improve the activity of the electrocatalytic CO2 reduction reaction (CO2RR), but it still remains a challenge due to the short excited-state lifetime of active sites. Herein, Ru(bpy)3Cl2 struts as powerful photosensitive donors were immobilized into the backbones of Co-porphyrin-based covalent organic frameworks (named Co-Bpy-COF-Rux, x is the molar ratio of Ru and Co species, x = 1/2 and 2/3) via coordination bonds, for the photo-coupled CO2RR to produce CO. The optimal Co-Bpy-COF-Ru1/2 displays a high CO Faradaic efficiency of 96.7% at -0.7 V vs reversible hydrogen electrode (RHE) and a CO partial current density of 16.27 mA cm-2 at -1.1 V vs RHE under the assistance of light, both of which were far surpassing the values observed in the dark. The significantly enhanced activity is mainly attributed to the incorporation of a Ru(bpy)3Cl2 donor with long excited-state lifetime and concomitantly giant built-in electric field in Co-Bpy-COF-Ru1/2, which efficiently accelerate the photo-induced electron transfer from Ru(bpy)3Cl2 to the cobalt-porphyrin under the external light. Thus, the cobalt-porphyrin active sites have a longer excited-state lifetime to lower the rate-determining steps' energy occurring during the actual photo-coupled electrocatalytic CO2RR process. This is the first work of porphyrin-based COFs for photo-coupled CO2RR, opening a new frontier for the construction of efficient photo-coupled electrocatalysts.

Tandem Photocatalysis of CO2 to C2H4 via a Synergistic Rhenium-(I) Bipyridine/Copper-Porphyrinic Triazine Framework.

The photocatalytic conversion of CO2 into C2+ products such as ethylene is a promising path toward the carbon neutral goal but remains a big challenge due to the high activation barrier for CO2 and similar reduction potentials of many possible multi-electron-transfer products. Herein, an effective tandem photocatalysis strategy has been developed to support conversion of CO2 to ethylene by construction of the synergistic dual sites in rhenium-(I) bipyridine fac-[ReI(bpy)(CO)3Cl] (Re-bpy) and copper-porphyrinic triazine framework [PTF(Cu)]. With these two catalysts, a large amount of ethylene can be produced at a rate of 73.2 µmol g-1 h-1 under visible light irradiation. However, ethylene cannot be obtained from CO2 by use of either component of the Re-bpy or PTF(Cu) catalysts alone; with a single catalyst, only monocarbon product CO is produced under similar conditions. In the tandem photocatalytic system, the CO generated at the Re-bpy sites is adsorbed by the nearby Cu single sites in PTF(Cu), and this is followed by a synergistic C-C coupling process which ultimately produces ethylene. Density functional theory calculations demonstrate that the coupling process between PTF(Cu)-*CO and Re-bpy-*CO to form the key intermediate Re-bpy-*CO-*CO-PTF(Cu) is vital to the C2H4 production. This work provides a new pathway for the design of efficient photocatalysts for photoconversion of CO2 to C2 products via a tandem process driven by visible light under mild conditions.

Real-Time Imaging of Single Viral mRNA Translation in Live Cells Using CRISPR/dCas13.

Translation is one of the many critical cellular activities regulated by viruses following host-cell invasion, and studies of viral mRNA translation kinetics and subcellular localization require techniques for the dynamic, real-time visualization of translation. However, conventional tools for imaging mRNA translation often require coding region modifications that may affect native translation. Here, we achieve dynamic imaging of translation with a tool that labels target mRNAs with unmodified coding regions using a CRISPR/dCas13 system with specific complementary paired guide RNAs. This system enables a real-time dynamic visualization of the translation process and is a promising tool for further investigations of the mechanisms of translation.

Maize (Zea mays L.) planted at higher density utilizes dynamic light more efficiently.

In nature, plants are exposed to a dynamic light environment. Fluctuations in light decreased the photosynthetic light utilization efficiency (PLUE) of leaves, and much more severely in C4 species than in C3 species. However, little is known about the plasticity of PLUE under dynamic light in C4 species. Present study focused on the influence of planting density to the photosynthesis under dynamic light in maize (Zea mays L.), a most important C4 crop. In addition, the molecular mechanism behind photosynthetic adaptation to planting density were also explored by quantitative proteomics analysis. Results revealed that as planting density increases, maize leaves receive less light that fluctuates more. The maize planted at high density (HD) improved the PLUE under dynamic light, especially in the middle and later growth stages. Quantitative proteomics analysis showed that the transfer of nitrogen from Rubisco to RuBP regeneration and C4 pathway related enzymes contributes to the photosynthetic adaptation to lower and more fluctuating light environment in HD maize. This study provides potential ways to further improve the light energy utilization efficiency of maize in HD.

Thermo-, Electro-, and Photocatalytic CO2 Conversion to Value-Added Products over Porous Metal/Covalent Organic Frameworks.

ConspectusThe continuing increase of the concentration of atmospheric CO2 has caused many environmental issues including climate change. Catalytic conversion of CO2 using thermochemical, electrochemical, and photochemical methods is a potential technique to decrease the CO2 concentration and simultaneously obtain value-added chemicals. Due to the high energy barrier of CO2 however, this method is still far from large-scale applications which requires high activity, selectivity, and stability. Therefore, development of efficient catalysts to convert CO2 to different products is urgent. With their well-engineered pores and chemical compositions, high surface area, elevated CO2 adsorption capability, and adjustable active sites, porous crystalline frameworks including metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) are potential materials for catalytic CO2 conversion. Here, we summarize our recent work on MOFs and COFs for thermocatalytic, electrocatalytic, and photocatalytic CO2 conversion and describe the structure-activity relationships that could guide the design of effective catalysts.The first section of this paper describes imidazolium-functionalized porous MOFs, including porous liquid and cationic MOFs with nucleophilic halogen ions, which can promote thermocatalytically CO2 cycloaddition reaction with epoxides toward cyclic carbonates at one bar pressure. A porous liquid MOF takes on the role of a CO2 reservoir to tackle the low local CO2 concentrations in gas-liquid-solid heterogeneous reactions. Imidazolium-functionalized MOFs with halogen ions for CO2 cycloaddition could avoid the use of cocatalysts, and this leads to milder and more facile experimental conditions and separation processes.In a section dealing with the electrocatalytic CO2 reduction reaction (CO2RR), we developed a series of conductive porous framework materials with fast electron transmission capabilities, which afford high current densities and outperform the traditional MOF and COF catalysts that have been reported. The intrinsically conductive two-dimensional 2D MOFs and COFs nanosheets based on the fully π-conjugated phthalocyanine motif with excellent electron transport capability were prepared, and strong electron transporters were also integrated into metalloporphyrin-based COFs for CO2RR. Cu2O quantum dots and Cu nanoparticles (NPs) can be uniformly dispersed on porous conductive MOFs/COFs to afford synergistic and/or tandem electrocatalysts, which can achieve highly selective production of CH4 or C2H4 in CO2RR.A third section describes our efforts to facilitate electron-hole separation in CO2 photocatalysis. Our focus is on regulation of coordination spheres in MOFs, fabrication of the architecture of MOF heterojunctions, and engineering MOF films to facilitate photocatalytic CO2 reduction.Finally, we discuss several problems associated with the studies of MOFs and COFs for CO2 conversion and consider some prospects of the fabrication of effective porous frameworks for CO2 adsorption and conversion.

Nanotheranostics in cancer lymph node metastasis: The long road ahead.

Lymph node metastasis (LNM) significantly impacts the prognosis of cancer patients. Despite significant advancements in diagnostic techniques and treatment modalities, clinical challenges continue to persist in the realm of LNM. These include difficulties in early diagnosis, limited treatment efficacy, and potential side effects and injuries associated with treatment. Nanotheranostics, a field within nanotechnology, seamlessly integrates diagnostic and therapeutic functionalities. Its primary goal is to provide precise and effective disease diagnosis and treatment simultaneously. The development of nanotheranostics for LNM offers a promising solution for the stratified management of patients with LNM and promotes the advancement of personalized medicine. This review introduces the mechanisms of LNM and challenges in its diagnosis and treatment. Furthermore, it demonstrates the advantages and development potential of nanotheranostics, focuses on the challenges nanotheranostics face in its application, and provides an outlook on future trends. We consider nanotheranostics a promising strategy to improve clinical effectiveness and efficiency as well as the prognosis of cancer patients with LNM.

Identification and characterization of two SERPINC1 mutations causing congenital antithrombin deficiency.

BACKGROUND: Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. METHODS: Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. RESULTS: The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. CONCLUSIONS: The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

Dynamic regulation of excitatory and inhibitory synaptic transmission by growth hormone in the developing mouse brain.

Normal sensory and cognitive function of the brain relies on its intricate and complex neural network. Synaptogenesis and synaptic plasticity are critical to neural circuit formation and maintenance, which are regulated by coordinated intracellular and extracellular signaling. Growth hormone (GH) is the most abundant anterior pituitary hormone. Its deficiencies could alter brain development and impair learning and memory, while GH replacement therapy in human patients and animal models has been shown to ameliorate cognitive deficits caused by GH deficiency. However, the underlying mechanism remains largely unknown. In this study, we investigated the neuromodulatory function of GH in young (pre-weaning) mice at two developmental time points and in two different brain regions. Neonatal mice were subcutaneously injected with recombinant human growth hormone (rhGH) on postnatal day (P) 14 or 21. Excitatory and inhibitory synaptic transmission was measured using whole-cell recordings in acute cortical slices 2 h after the injection. We showed that injection of rhGH (2 mg/kg) in P14 mice significantly increased the frequency of mEPSCs, but not that of mIPSCs, in both hippocampal CA1 pyramidal neurons and L2/3 pyramidal neurons of the barrel field of the primary somatosensory cortex (S1BF). Injection of rhGH (2 mg/kg) in P21 mice significantly increased the frequency of mEPSCs and mIPSCs in both brain regions. Perfusion of rhGH (1 µM) onto acute brain slices in P14 mice had similar effects. Consistent with the electrophysiological results, the dendritic spine density of CA1 pyramidal neurons and S1BF L2/3 pyramidal neurons increased following in vivo injection of rhGH. Furthermore, NMDA receptors and postsynaptic calcium-dependent signaling contributed to rhGH-dependent regulation of both excitatory and inhibitory synaptic transmission. Together, these results demonstrate that regulation of excitatory and inhibitory synaptic transmission by rhGH occurs in a developmentally dynamic manner, and have important implication for identifying GH treatment strategies without disturbing excitation/inhibition balance.

Effect of glutamine on the systemic innate immune response in broiler chickens challenged with Salmonella pullorum.

BACKGROUND: The objective of this study was to evaluate the effects of glutamine on the growth performance and systemic innate immune response in broiler chickens challenged with Salmonella pullorum. A total of 600 one-day-old Arbor Acres broiler chickens were assigned randomly to 6 dietary treatments with 10 replicates for a 21-day feeding experiment. The experimental treatments were as follows: the control treatment (birds fed the basal diet), the Gln1 treatment, and the Gln 2 treatment (birds fed the basal diet supplemented with 0.5%, and 1.0% Glutamine, respectively). At 3 d of age, half of the birds from each treatment were challenged oral gavage with 2.0 × 104 CFU/mL of S. pullorum suspension (1.0 mL per bird) or an equivalent amount of sterile saline alone, which served as a control. RESULTS: The results showed that S. pullorum infection had adverse effects on the average daily feed intake, average daily gain, and feed conversion ratio of broiler chickens compared with those of the CON treatment on d 7, decreased the spleen and bursa of fabricius relative weights (except on d 21), serum immunoglobulin A (IgA),immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations, and spleen melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology gene 2 (LGP2) mRNA expression levels, and increased the mRNA expression levels of spleen Nodinitib-1 (NOD1), Toll-like receptors 2,4 (TLR2, TLR4), DNA-dependent activator of IFN-regulatory factors (DAI), mitochondrial antiviral-signaling protein (MAVS), P50, P65, and RelB on d 4, 7, 14, and 21. Supplementation with Gln improved the relative weights of the spleen and bursa of Fabricius (except on d 21), increased the serum IgA, IgG, and IgM concentrations and the mRNA expression levels of spleen MDA5 and LGP2, and decreased the mRNA expression levels of spleen NOD1, TLR2, TLR4, DAI, MAVS, P50, P65, and RelB of S. pullorum-challenged broiler chickens. CONCLUSION: These results indicate that Gln might stimulate the systemic innate immune responses of the spleen in broiler chickens challenged with S. pullorum.

Han family with essential tremor caused by the P421L variant of the TENM4 gene in China.

BACKGROUND: Essential tremor (ET) is an autosomal dominant inheritance disorder. Mutations in fusion sarcoma (FUS), mitochondrial serine peptidase 2 (HTRA2), teneurin transmembrane protein 4 (TENM4), sortilin1 (SORT1), SCN11A, and notch2N-terminal-like (NOTCH2NLC) genes are associated with familial ET. METHODS: A proband with ET was tested using whole-exome sequencing and repeat-primed polymerase chain reaction. Subsequently, the family members were screened for the suspected mutation, and the results were verified using Sanger sequencing. The relationship between pedigree and phenotype was also analyzed, and structural and functional changes in the variants were predicted using bioinformatics analysis. RESULTS: In a family with ET, the proband (III4) and the proband's father (II1), grandfather (I1), uncle (II2), and cousin (III5) all presented with involuntary tremors of both upper limbs. The responsible mutation was identified as TENM4 c.1262C > T (p.P421L), which showed genetic co-segregation in the family survey. AlphaFold predicted a change in the spatial position of TENM4 after the P421L mutation, which may have affected its stability. AlphaFold also predicted P421L to be a deleterious variation, which would lead to lower degrees of freedom of the TENM4 protein, thereby affecting the protein's structure and stability. According to the bioinformatics analysis, TENM4 (p.P421L) may reduce the signal reaching the nucleus by affecting the expression of TENM4 messenger RNA (mRNA), thereby impairing the normal oligodendrocyte differentiation process and leading to impaired myelination. CONCLUSION: This study revealed that the TENM4 (p.P421L) pathogenic missense variation was responsible for ET in the proband.

Calcineurin inhibitors or cyclophosphamide in the treatment of membranous nephropathy superimposed with FSGS lesions: a retrospective study from China.

BACKGROUND: Cyclophosphamide (CTX) and calcineurin inhibitors (CNIs) based regimens are recommended as immunosuppressive therapies for patients with idiopathic membranous nephropathy (IMN). Focal and segmental glomerular sclerosis (FSGS) lesions, which are common in membranous nephropathy (MN), are poor predictors of outcome. This study compared the differences of prognosis between two regimens in patients with IMN combined with FSGS lesions. METHODS: This retrospective study enrolled 108 patients with biopsy-proven IMN, accompanied with FSGS lesions, nephrotic syndrome and an estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2 who were treated with CTX or CNIs. We used propensity score matching (PSM) for balancing the confounding variables. RESULTS: During follow-up, 10 patients (10/55 [18.2%]; nine males) in the CNIs group showed a 50% decline in eGFR; eight had a not otherwise specified variant. Patients initially treated with CNIs had a significantly higher risk of progression to the primary outcome and a lower probability of complete or total remission. The relapse rate was higher in patients who initially received CNIs- than in those who received CTX-based treatment. Before PSM, age and 24-h urine protein level differed significantly between the groups. The PSM model included data from 72 patients. Worse outcomes were also noted among patients who initially received CNIs than those who received CTX-based treatments after matching. CONCLUSIONS: Patients with MN combined with FSGS lesions have a higher risk of renal functional decline and a higher rate of relapse after CNIs than after CTX therapy.

Study on the Dynamic Changes in Non-Volatile Metabolites of Rizhao Green Tea Based on Metabolomics.

The processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based on UHPLC-Q Exactive MS. Totals of 529, 349, and 206 non-volatile metabolites were identified using three different detection modes, of which 112 secondary metabolites were significantly changed. Significant variations in secondary metabolites were observed during processing, especially during the drying stage, and the conversion intensity levels of non-volatile metabolites were consistent with the law of "Drying > Fixation > Rolling". The DOT method was used to screen tea-quality-related compounds that contributed significantly to the taste of Rizhao green tea, including (-)-epicatechin gallate, (-)-epicatechin gallate, gallic acid, L-theanine, and L-leucine, which make important contributions to taste profiles, such as umami and bitterness. Metabolic pathway analysis revealed that purine metabolism, caffeine metabolism, and tyrosine metabolism perform key roles in the processing of Rizhao green tea in different processing stages. The results of this study provide a theoretical basis for tea processing and practical advice for the food industry.

Boosting Electroreduction of CO2 over Cationic Covalent Organic Frameworks: Hydrogen Bonding Effects of Halogen Ions.

We present the first example of charged imidazolium functionalized porphyrin-based covalent organic framework (Co-iBFBim-COF-X) for electrocatalytic CO2 reduction reaction, where the free anions (e.g., F- , Cl- , Br- , and I- ) of imidazolium ions nearby the active Co sites can stabilize the key intermediate *COOH and inhibit hydrogen evolution reaction. Thus, Co-iBFBim-COF-X exhibits higher activity than the neutral Co-BFBim-COF, following the trend of F-

Atomically Precise Copper Nanoclusters for Highly Efficient Electroreduction of CO2 towards Hydrocarbons via Breaking the Coordination Symmetry of Cu Site.

We propose an effective highest occupied d-orbital modulation strategy engendered by breaking the coordination symmetry of sites in the atomically precise Cu nanocluster (NC) to switch the product of CO2 electroreduction from HCOOH/CO to higher-valued hydrocarbons. An atomically well-defined Cu6 NC with symmetry-broken Cu-S2 N1 active sites (named Cu6 (MBD)6 , MBD=2-mercaptobenzimidazole) was designed and synthesized by a judicious choice of ligand containing both S and N coordination atoms. Different from the previously reported high HCOOH selectivity of Cu NCs with Cu-S3 sites, the Cu6 (MBD)6 with Cu-S2 N1 coordination structure shows a high Faradaic efficiency toward hydrocarbons of 65.5 % at -1.4 V versus the reversible hydrogen electrode (including 42.5 % CH4 and 23 % C2 H4 ), with the hydrocarbons partial current density of -183.4 mA cm-2 . Theoretical calculations reveal that the symmetry-broken Cu-S2 N1 sites can rearrange the Cu 3d orbitals with d x 2 - y 2 ${d_{x^2 - y^2 } }$ as the highest occupied d-orbital, thus favoring the generation of key intermediate *COOH instead of *OCHO to favor *CO formation, followed by hydrogenation and/or C-C coupling to produce hydrocarbons. This is the first attempt to regulate the coordination mode of Cu atom in Cu NCs for hydrocarbons generation, and provides new inspiration for designing atomically precise NCs for efficient CO2 RR towards highly-valued products.

Mice and Rats Exhibit Striking Inter-species Differences in Gene Response to Acute Stroke.

Neuroprotection in acute stroke has not been successfully translated from animals to humans. Animal research on promising agents continues largely in rats and mice which are commonly available to researchers. However, controversies continue on the most suitable species to model the human situation. Generally, putative agents seem less effective in mice as compared with rats. We hypothesized that this may be due to inter-species differences in stroke response and that this might be manifest at a genetic level. Here we used whole-genome microarrays to examine the differential gene regulation in the ischemic penumbra of mice and rats at 2 and 6 h after permanent middle cerebral artery occlusion (pMCAO; Raw microarray CEL data files are available in the GEO database with an accession number GSE163654). Differentially expressed genes (adj. p ≤ 0.05) were organized by hierarchical clustering, correlation plots, Venn diagrams and pathway analyses in each species and at each time-point. Emphasis was placed on genes already known to be associated with stroke, including validation by RT-PCR. Gene expression patterns in the ischemic penumbra differed strikingly between the species at both 2 h and 6 h. Nearly 90% of significantly regulated genes and most pathways modulated by ischemia differed between mice and rats. These differences were evident globally, among stroke-associated genes, immediate early genes, genes implicated in stress response, inflammation, neuroprotection, ion channels, and signal transduction. The findings of this study may have significant implications for the choice of species for screening putative stroke therapies.

Tailoring Hybrid Aluminoborate Frameworks by Incorporating Multicomponent Cadmium-Amine Complexes with Various Conformations.

Inorganic-organic hybrid aluminoborates represent a subclass of porous materials, which rely on effective construction method and structure-directing agents. Herein, we prepared a series of hybrid aluminoborates through covalent decoration of unsaturated Cd2+ complexes, whose formation take advantage of chelating amine and long-chain diamine as mixed ligands. These isolated compounds, that is, [Cd(en)(1,4-dab)0.5][AlB5O10] (1a; its analogue with discrete complex [Cd(en)(dien)H2O][AlB5O10] is denoted as 1b), [Cd(1,2-dap)1.5(1,4-dabH)0.5]{Al[B5O8(OH)2](B5O10)0.5} (2), and [Cd(en)(1,3-dap)][AlB5O10] (3) feature open frameworks (1a, 1b, and 3) or a sandwich-like porous layer (2) that are constructed by AlO4 tetrahedra and [B5O10]5-/[B5O8(OH)2]3- clusters. However, they exhibit different structural features in interconnection, channel environment, and topology as a result of diversified interactions between unsaturated complexes and aluminoborate frameworks, that is, through forming two Cd-O bonds with (i) a pair of neighboring BO3 and AlO4, (ii) the same AlO4, or (iii) the same BO3. The variation in connection mode exerts essential influence on binding effects and steric hindrance that are reflected by changes in interatomic distance, bond angle, window configuration, and interlinkage of units. In addition, the incorporation of unsaturated Cd2+ complexes endows these aluminoborate materials with photoluminescence function. Compound 3 with a noncentrosymmetric structure exhibits second harmonic generation (SHG) response approximately 0.7 times that of KDP. The preparation strategy for hybrid aluminoborates proposed here combines well molecular design with templating assembly, whose synergistic effect would be crucial for drawing a rational pathway for inorganic synthesis, especially with focus on structural and functional innovation.