Single-cell and spatial sequencing identifies senescent and germinal tumor cells in adamantinomatous craniopharyngiomas.

Adamantinomatous craniopharyngioma (ACP) is a clinically aggressive tumor without effective treatment method. Previous studies proposed a paracrine tumorigenesis model, in which oncogenic ß-catenin induces senescence in pituitary stem cells and the senescent cells lead the formation of paracrine tumors through secretion of pro-tumorigenic factors. However, there lacks characterization on senescent cells in ACPs. Here, we profiled 12 ACPs with single-cell RNA and TCR-sequencing to elucidate the cellular atlas in ACPs and 3 of them were also subject to spatial sequencing to localize different subpopulations of the tumor cells. In total, we obtained the transcriptome profiles of 70,682 cells. Tumor cells, which were unambiguously identified through the cellular mutation status of the driver CTNNB1 mutations, were clustered into 6 subsets. The whorl-like cluster (WC) cells show distinct molecular features from the other tumor cells and the palisading epithelium (PE) cells consists of a proliferating subset. Other than typical PE and WC, we identified two novel subpopulations of the tumor cells. In one subpopulation, the cells express a high level of cytokines, e.g., FDCSP and S100A8/A9, and are enriched with the senescence-associated secretory phenotype (SASP) factors. Hematoxylin and eosin staining reveals that these SASP cells lack an ordered structures and their nuclei are elongated. In the other subpopulation, the cell sizes are small and they are tightly packed together with an unusual high density expressing a high level of mitochondrial genes (median 10.9%). These cells are the origin of the tumor developmental trajectories revealed by RNA velocity and pseudo-time analysis. Single-cell RNA and TCR analysis reveals that some ACPs are infiltrated with clonally expanded cytotoxic T cells. We propose a hypothesis that WC and PE are formed via different negative regulation mechanisms of the overactivated WNT/ß-catenin signaling which provides a new understanding on the tumorigenesis of ACPs. The study lays a foundation for future studies on targeting senescent cells in ACPs with senolytic compounds or other therapeutic agents.

Visual monitoring of cisplatin-regulated caspase-3 activity in living cells based on a reduced graphene oxide-loaded fluorescent probe.

Cisplatin (DDP) is a potent chemotherapeutic drug, which can regulate tumor cell apoptosis by up-regulating caspase-3 activity. Thus, monitoring caspase-3 activity in breast cancer cells can directly illustrate the efficiency of DDP treatment. In this study, by using reduced graphene oxide (rGO) as a quencher of a fluorescence labeled peptide, we developed an "off to on" method to monitor the effect of DDP on caspase-3 in breast cancer cells. In this method, the rGO quenched fluorescence with an ultra-high level of efficiency. Caspase-3 hydrolyzed the polypeptide probe, generating two segments of different lengths. The release of a short segment marked with fluorophores led to the recovery of the fluorescence signal (Ex/Em = 450/521 nm). Under the optimal conditions, the linear range of caspase-3 was 0.4-7 U mL-1 and the limit of detection was 0.33 U mL-1. The upregulating effect of DDP on intracellular caspase-3 activity was visualized with the "off to on" method and flow cytometry assay showed that caspase-3 activity increased along with the apoptosis rate of tumor cells. The above results show the practical application of the method for evaluating the efficacy of drugs against cancer cells.

Seismic response of mountain tunnel induced by fault slip.

With the rapid development of Chinese transportation networks, such as the Sichuan-Tibet railway, numerous tunnels are under construction or planned in mountainous regions. Some of these tunnels must traverse or be situated near active fault zones, which could suffer damage from fault slip. In this study, the seismic response of a mountain tunnel subjected to coseismic faulting was analyzed using a fault-structure system in a two-step process. Firstly, a nonuniform slip model was proposed to calculate the ground deformations and internal displacements induced by a specific active fault on a geological scale, considering nonuniform slips on the fault plane. The 1989 Loma Prieta and 2022 Menyuan earthquakes were chosen as case studies to validate the proposed slip model. Secondly, the calculated displacement of the Menyuan earthquake was used as the input load for the discrete-continuous coupling analysis of the Daliang tunnel on an engineering scale. The simulated deformation of the Daliang tunnel aligned with the on-site damage observations following the Menyuan earthquake. Lastly, the effects of different fault conditions on the tunnel seismic response were investigated. The results indicate that the distribution of the peak longitudinal strain of the lining is governed by fault mechanisms, and the degree of fault slip significantly influences the response of the tunnel. A tunnel passing through an active fault with a wider fault fracture zone and smaller dip angle experience less damage.

Nutritional support clinical efficacy in tuberculosis: quasi-experimental study.

OBJECTIVE: This study aimed to investigate the impact of nutritional support on the clinical efficacy in hospitalised tuberculosis patients with nutritional risk. METHODS: We selected a total of 266 eligible patients with tuberculosis for the experimental and 190 patients for control groups. The patients in intervention group received adjusted dietary structure, enteral nutrition via oral intake or gastric tube, total parenteral nutrition and combined enteral and parenteral nutrition. We recorded various factors, including age, sex, underlying disease, tuberculosis type, nutritional risk at admission, serum albumin (ALB), body mass index, complications during hospitalisation, nutritional support status, serum ALB before discharge and length of hospital stay. RESULTS: The incidences of nutritional risk in the control and experimental groups were 64.41% and 64.72%, respectively, with no statistically significant differences in baseline characteristics. The occurrence rates of complications and secondary infections in the experimental group were 57.89% and 51.5%, respectively, which were significantly lower than the control group's rates of 70.00% and 56.31%. These differences were statistically significant. The experimental group had a significantly shorter hospital stay (16.5±7.54 days) compared with the control group (19.55±7.33 days). Furthermore, the serum ALB levels of patients in the experimental group were higher on discharge than at admission. CONCLUSION: Hospitalised patients with tuberculosis often face a high incidence of nutritional risk. However, the implementation of standardised nutritional support treatment has shown promising results in improving the nutritional status of tuberculosis patients with nutritional risk. This approach not only helps reduce the occurrence of complications but also enhances short-term prognosis and improves overall clinical efficacy.

X-Box binding protein 1 downregulates SIRT6 to promote injury in pancreatic ductal epithelial cells.

OBJECTIVE: Acute pancreatitis (AP) stands as a frequent cause for clinical emergency hospital admissions. The X-box binding protein 1 (XBP1) was found to be implicated in pancreatic acinar cell apoptosis. The objective is to unveil the potential mechanisms governed by XBP1 and SIRT6 in the context of AP. METHODS: Caerulein-treated human pancreatic duct epithelial (HPDE) cells to establish an in vitro research model. The levels and regulatory role of SIRT6 in the treated cells were evaluated, including its effects on inflammatory responses, oxidative stress, apoptosis, and endoplasmic reticulum stress. The relationship between XBP1 and SIRT6 was explored by luciferase and ChIP experiments. Furthermore, the effect of XBP1 overexpression on the regulatory function of SIRT6 on cells was evaluated. RESULTS: Caerulein promoted the decrease of SIRT6 and the increase of XBP1 in HPDE cells. Overexpression of SIRT6 slowed down the secretion of inflammatory factors, oxidative stress, apoptosis level, and endoplasmic reticulum stress in HPDE cells. However, XBP1 negatively regulated SIRT6, and XBP1 overexpression partially reversed the regulation of SIRT6 on the above aspects. CONCLUSION: Our study illuminates the role of XBP1 in downregulating SIRT6 in HPDE cells, thereby promoting cellular injury. Inhibiting XBP1 or augmenting SIRT6 levels holds promise in preserving cell function and represents a potential therapeutic avenue in the management of AP.

Decreasing Greenhouse Gas Emissions from the Municipal Solid Waste Sector in Chinese Cites.

Municipal solid waste (MSW) management systems play a crucial role in greenhouse gas (GHG) emissions in China. Although the government has implemented many policies to improve the MSW management system, the impact of these improvements on city-level GHG emission reduction remains largely unexplored. This study conducted a comprehensive analysis of both direct and downstream GHG emissions from the MSW sector, encompassing sanitary landfill, dump, incineration, and biological treatment, across 352 Chinese cities from 2001 to 2021 by adopting inventory methods recommended by the Intergovernmental Panel on Climate Change (IPCC). The results reveal that (1) GHG emissions from the MSW sector in China peaked at 70.6 Tg of CO2 equiv in 2018, followed by a significant decline to 47.6 Tg of CO2 equiv in 2021, (2) cities with the highest GHG emission reduction benefits in the MSW sector were historical emission hotspots over the past 2 decades, and (3) with the potential achievement of zero-landfilling policy by 2030, an additional reduction of 203.7 Tg of CO2 equiv is projected, with the emission reduction focus toward cities in South China (21.9%), Northeast China (17.8%), and Southwest China (17.3%). This study highlights that, even without explicit emission reduction targets for the MSW sector, the improvements of this sector have significantly reduced GHG emissions in China.

Efficacy and Safety of Insulin Degludec/Insulin Aspart versus Biphasic Insulin Aspart 30 in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

Background: We systematically reviewed and analyzed the efficacy and safety of insulin degludec/insulin as-part (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes (T2D). Methods: We used computers to search the Embase, PubMed, Clinical Trials, and the Cochrane Library database, and collected randomized controlled trials (RCTs) on the treatment of IDegAsp versus BIAsp 30 in T2D patients. The research period was from the establishment of the database to May 19, 2023. We used Review Manager 5.20 statistical software for systematic meta-analysis. Results: We included 8 RCTs with 2281 participants. IDegAsp was better to BIAsp30 in improving fasting plasma glucose (FPG) levels (P<0.001) and reducing the endpoint daily average insulin dose (P<0.01). Furthermore, compared with BIAsp30, IDegAsp significantly reduced the risk of nocturnal hypoglycemic events (P<0.001). However, there was no significant difference in the improvement of body weight change (P=0.99), glycosylated hemoglobin (P=0.50), the overall risk of hypoglycemic events (P=0.57) and adverse events (P=0.89) between the two groups. Conclusion: Compared with BIAsp30, IDegAsp could significantly reduce FPG levels, insulin dosage, and the risk of nocturnal hypoglycemic events in T2D patients, without increasing the overall risk of adverse events.

In Situ Aggregated Nanomanganese Enhances Radiation-Induced Antitumor Immunity.

Radiosensitizers play a pivotal role in enhancing radiotherapy (RT). One of the challenges in RT is the limited accumulation of nanoradiosensitizers and the difficulty in activating antitumor immunity. Herein, a smart strategy was used to achieve in situ aggregation of nanomanganese adjuvants (MnAuNP-C&B) to enhance RT-induced antitumor immunity. The aggregated MnAuNP-C&B system overcomes the shortcomings of small-sized nanoparticles that easily flow back into blood vessels and diffuse into surrounding tissues, and it also prolongs the retention time of nanomanganese within cancer cells and tumors. The MnAuNP-C&B system significantly enhances the radiosensitization effect in RT. Additionally, the pH-responsive disassembly of MnAuNP-C&B triggers the release of Mn2+, further promoting RT-induced activation of the STING pathway and eliciting robust antitumor immunity. Overall, our study presents a smart strategy wherein in situ aggregation of nanomanganese effectively inhibits tumor growth through radiosensitization and the activation of antitumor immunity.

Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.

PURPOSE: Diffuse midline glioma (DMG), H3 K27M-mutant is a type of diffuse high-grade glioma that occurs in the brain midline carrying an extremely poor prognosis under the best efforts of surgery, radiation, and other therapies. For better therapy, we explored the efficacy and toxicity of a novel therapy that combines apatinib and temozolomide in DMG. METHODS: A retrospective analysis of 32 patients with DMG who underwent apatinib plus temozolomide treatment was performed. Apatinib was given 500 mg in adults, 250 mg in pediatric patients once daily. Temozolomide was administered at 200 mg/m2/d according to the standard 5/28 days regimen. The main clinical data included basic information of patients, radiological and pathological characteristics of tumors, treatment, adverse reactions, prognosis. RESULTS: The objective response rate was 24.1%, and the disease control rate was 79.3%. The median PFS of all patients was 5.8 months, and median OS was 10.3 months. A total of 236 cycles of treatment were available for safety assessment and the toxicity of the combination therapy was relatively well tolerated. The most common grade 3 toxicities were myelosuppression including leukopenia (5.08%), neutropenia (4.24%), lymphopenia (2.12%), thrombocytopenia (1.69%) and anemia (1.27%). Grade 4 toxicities included neutropenia (2.12%), thrombocytopenia (2.12%) and proteinuria (1.69%). All the adverse events were relieved after symptomatic treatment or dose reduction. CONCLUSIONS: Apatinib plus temozolomide could be an effective regimen with manageable toxicities and favorable efficacy and may outperform temozolomide monotherapy, particularly in newly diagnosed adults with tumors located outside the pons. The novel therapy deserves further investigation in adult DMG patients.

Unlocking Efficiency: Minimizing Energy Loss in Electrocatalysts for Water Splitting.

Catalysts play a crucial role in water electrolysis by reducing the energy barriers for hydrogen and oxygen evolution reactions (HER and OER). Research aims to enhance the intrinsic activities of potential catalysts through material selection, microstructure design, and various engineering techniques. However, the energy consumption of catalysts has often been overlooked due to the intricate interplay among catalyst microstructure, dimensionality, catalyst-electrolyte-gas dynamics, surface chemistry, electron transport within electrodes, and electron transfer among electrode components. Efficient catalyst development for high-current-density applications is essential to meet the increasing demand for green hydrogen. This involves transforming catalysts with high intrinsic activities into electrodes capable of sustaining high current densities. This review focuses on current improvement strategies of mass exchange, charge transfer, and reducing electrode resistance to decrease energy consumption. It aims to bridge the gap between laboratory-developed, highly efficient catalysts and industrial applications regarding catalyst structural design, surface chemistry, and catalyst-electrode interplay, outlining the development roadmap of hierarchically structured electrode-based water electrolysis for minimizing energy loss in electrocatalysts for water splitting.

Challenges and Opportunities for Single-Atom Electrocatalysts: From Lab-Scale Research to Potential Industry-Level Applications.

Single-atom electrocatalysts (SACs) are a class of promising materials for driving electrochemical energy conversion reactions due to their intrinsic advantages, including maximum metal utilization, well-defined active structures, and strong interface effects. However, SACs have not reached full commercialization for broad industrial applications. This review summarizes recent research achievements in the design of SACs for crucial electrocatalytic reactions on their active sites, coordination, and substrates, as well as the synthesis methods. The key challenges facing SACs in activity, selectivity, stability, and scalability, are highlighted. Furthermore, it is pointed out the new strategies to address these challenges including increasing intrinsic activity of metal sites, enhancing the utilization of metal sites, improving the stability, optimizing the local environment, developing new fabrication techniques, leveraging insights from theoretical studies, and expanding potential applications. Finally, the views are offered on the future direction of single-atom electrocatalysis toward commercialization.

Synthesis of micro-crosslinked adamantane-containing matrix resins designed for deep-UV lithography resists and their application in nanoimprint lithography.

A certain type of photoresist used for deep-UV lithography (DUVL) can also be used for other types of photolithography. Thus, to meet the requirements of two or more lithography technologies simultaneously, it is necessary to design a variety of corresponding functional groups in the molecules of materials and obtain the required properties. Herein, we designed four matrix resins based on acrylate for DUVL, employing alkyl sulfide, adamantane, methyladamantane, and hydroxyl as dangling groups and a microcrosslinking network by adding a small amount of crosslinker. These polymers were used in the thermal nanoimprint lithography (NIL) process, and distinct patterns with a resolution of 100 nm were observed. The acrylate copolymers designed for DUVL in this work can be used as thermal NIL resists and to obtain good patterns. It was found that ethylene dimethacrylate (EDMA) and adamantane endowed the matrix resins with good thermal stability and that PMMHM demonstrated the best patterning performance among the four resins. These polymers can be applied in the manufacturing of high-density integrated circuits, nano-transistors, optoelectronic devices and other components in the future.

Stacking Fault-Enriched MoNi4/MoO2 Enables High-Performance Hydrogen Evolution.

Producing green hydrogen in a cost-competitive manner via water electrolysis will make the long-held dream of hydrogen economy a reality. Although platinum (Pt)-based catalysts show good performance toward hydrogen evolution reaction (HER), the high cost and scarce abundance challenge their economic viability and sustainability. Here, a non-Pt, high-performance electrocatalyst for HER achieved by engineering high fractions of stacking fault (SF) defects for MoNi4/MoO2 nanosheets (d-MoNi) through a combined chemical and thermal reduction strategy is shown. The d-MoNi catalyst offers ultralow overpotentials of 78 and 121 mV for HER at current densities of 500 and 1000 mA cm-2 in 1 M KOH, respectively. The defect-rich d-MoNi exhibits four times higher turnover frequency than the benchmark 20% Pt/C, together with its excellent durability (> 100 h), making it one of the best-performing non-Pt catalysts for HER. The experimental and theoretical results reveal that the abundant SFs in d-MoNi induce a compressive strain, decreasing the proton adsorption energy and promoting the associated combination of *H into hydrogen and molecular hydrogen desorption, enhancing the HER performance. This work provides a new synthetic route to engineer defective metal and metal alloy electrocatalysts for emerging electrochemical energy conversion and storage applications.

Enhanced immunosuppressive capability of mesenchymal stem cell-derived small extracellular vesicles with high expression of CD73 in experimental autoimmune uveitis.

BACKGROUND: Autoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73. METHODS: To investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73. RESULTS: Compared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion. CONCLUSION: Over-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.

MicroRNA-10 Family Promotes Renal Fibrosis through the VASH-1/Smad3 Pathway.

Renal fibrosis (RF) stands as a pivotal pathological process in the advanced stages of chronic kidney disease (CKD), and impeding its progression is paramount for delaying the advancement of CKD. The miR-10 family, inclusive of miR-10a and miR-10b, has been implicated in the development of various fibrotic diseases. Nevertheless, the precise role of miR-10 in the development of RF remains enigmatic. In this study, we utilized both an in vivo model involving unilateral ureteral obstruction (UUO) in mice and an in vitro model employing TGF-ß1 stimulation in HK-2 cells to unravel the mechanism underlying the involvement of miR-10a/b in RF. The findings revealed heightened expression of miR-10a and miR-10b in the kidneys of UUO mice, accompanied by a substantial increase in p-Smad3 and renal fibrosis-related proteins. Conversely, the deletion of these two genes led to a notable reduction in p-Smad3 levels and the alleviation of RF in mouse kidneys. In the in vitro model of TGF-ß1-stimulated HK-2 cells, the co-overexpression of miR-10a and miR-10b fostered the phosphorylation of Smad3 and RF, while the inhibition of miR-10a and miR-10b resulted in a decrease in p-Smad3 levels and RF. Further research revealed that miR-10a and miR-10b, through binding to the 3'UTR region of Vasohibin-1 (VASH-1), suppressed the expression of VASH-1, thereby promoting the elevation of p-Smad3 and exacerbating the progression of RF. The miR-10 family may play a pivotal role in RF.

Small extracellular vesicle-based delivery of interleukin-10 improves treatment of experimental autoimmune uveitis.

Non-infectious uveitis is an intraocular autoimmune disease mainly characterized by immune dysregulation of the eye, which may cause blindness if not well treated. Interleukin 10 (IL-10) is a potent cytokine with multiple immunoregulatory functions. However, it's in vivo activity is unstable owing to its inherent protein instability and short plasma half-life. Therefore, our previous research tried to establish IL-10-overexpressing MSC-sEVs (sEVs-IL10) using lentiviral transfection. While this approach indeed improved drug delivery, it also suffered from tedious procedures and limited loading efficiency. Accordingly, we constructed a novel MSC-sEVs-based delivery system for IL-10 (IL-10@sEVs) by sonication. The obtained formulation (IL-10@sEVs) had relatively higher loading efficiency and exerted a more profound immunomodulatory effect than sEVs-IL10 in vitro. Furthermore, IL-10@sEVs had significant therapeutic effects in a mouse model of experimental autoimmune uveitis (EAU) by decreasing the percentage of Th17 cells, increasing regulatory T cells in the eye, and draining lymph nodes. In summary, sonication outperforms conventional transfection methods for loading IL-10 into MSC-sEVs.

Design and Analysis of 5-DOF Compact Electromagnetic Levitation Actuator for Lens Control of Laser Cutting Machine.

In laser beam processing, the angle or offset between the auxiliary gas and the laser beam axis have been proved to be two new process optimization parameters for improving cutting speed and quality. However, a traditional electromechanical actuator cannot achieve high-speed and high-precision motion control with a compact structure. This paper proposes a magnetic levitation actuator which could realize the 5-DOF motion control of a lens using six groups of differential electromagnets. At first, the nonlinear characteristic of a magnetic driving force was analyzed by establishing an analytical model and finite element calculation. Then, the dynamic model of the magnetic levitation actuator was established using the Taylor series. And the mathematical relationship between the detected distance and five-degree-of-freedom was determined. Next, the centralized control system based on PID control was designed. Finally, a driving test was carried out to verify the five-degrees-of-freedom motion of the proposed electromagnetic levitation actuator. The results show it can achieve a stable levitation and precision positioning with a desired command motion. It also proves that the proposed magnetic levitation actuator has the potential application in an off-axis laser cutting machine tool.

Work Function-Guided Electrocatalyst Design.

The development of high-performance electrocatalysts for energy conversion reactions is crucial for advancing global energy sustainability. The design of catalysts based on their electronic properties (e.g., work function) has gained significant attention recently. Although numerous reviews on electrocatalysis have been provided, no such reports on work function-guided electrocatalyst design are available. Herein, a comprehensive summary of the latest advancements in work function-guided electrocatalyst design for diverse electrochemical energy applications is provided. This includes the development of work function-based catalytic activity descriptors, and the design of both monolithic and heterostructural catalysts. The measurement of work function is first discussed and the applications of work function-based catalytic activity descriptors for various reactions are fully analyzed. Subsequently, the work function-regulated material-electrolyte interfacial electron transfer (IET) is employed for monolithic catalyst design, and methods for regulating the work function and optimizing the catalytic performance of catalysts are discussed. In addition, key strategies for tuning the work function-governed material-material IET in heterostructural catalyst design are examined. Finally, perspectives on work function determination, work function-based activity descriptors, and catalyst design are put forward to guide future research. This work paves the way to the work function-guided rational design of efficient electrocatalysts for sustainable energy applications.

Manganese(I)-Catalyzed Enantioselective C(sp2)-C(sp3) Bond-Forming for the Synthesis of Skipped Dienes with Synergistic Aminocatalysis.

Mn(I)-catalyzed enantioselective C-C bond-forming reactions represent a great challenge in homogeneous catalysis primarily due to a limited understanding of its mechanistic principles. Herein, we have developed an interesting catalytic strategy that leverages a synergistic combination of a dimeric manganese(I) catalyst and a chiral aminocatalyst to address this issue. A range of conjugated dienals and trienals can exclusively proceed 1,4-hydroalkenylation by using readily available aromatic and aliphatic alkenyl boronic acids as coupling partners, producing a rich library of skipped diene aldehydes in synthetically useful yields and high levels of enantioselectivities. Notably, downstream transformations of these products can not only afford a concise approach to construct enantioenriched skipped trienes but also realize enantioselective total synthesis of analogues to (-)-Blepharocalyxin D in four steps. DFT calculations suggest the 1,4-hydroalkenylation is kinetically more favorable than 1,6-hydroalkenylation.