Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Mechanistic insights into the changes of biological activity and physicochemical characteristics in Lacticaseibacillus paracasei fortified milk powder during storage.

To clarify the change mechanism of biological activity and physicochemical characteristics in Lacticaseibacillus paracasei JY025 fortified milk powder (LFMP) during storage, morphological observation, JY025 survival, storage stability, and metabolomics of LFMP were determined during the storage period in this study. The results showed that the LFMP had a higher survival rate of JY025 compared with the bacterial powder of JY025 (LBP) during storage, which suggested that milk powder matrix could reduce strain JY025 mortality under prolonged storage in the LFMP samples. The fortification of strain JY025 also affected the stability of milk powder during the storage period. There was lower water activity and higher glass transition temperature in LFMP samples compared with blank control milk powder (BCMP) during storage. Moreover, the metabolomics results of LFMP indicated that vitamin degradation, Maillard reaction, lipid oxidation, tricarboxylic acid cycle, and lactobacilli metabolism are interrelated and influence each other to create complicated metabolism networks.

Association between surrogate marker of insulin resistance and bone mineral density in US adults without diabetes.

This study examines the relationship between TyG-BMI, an indicator of insulin resistance, and bone mineral density in US adults without diabetes, revealing a positive association. The findings suggest that higher TyG-BMI levels may be linked to a lower risk of osteoporosis, providing a basis for future research in this area. OBJECTIVE: Patients with osteoporosis are often diagnosed with type 2 diabetes or prediabetes. Insulin resistance is a prediabetic state, and triglyceride glucose-body mass index (TyG-BMI) has been recognized as a potential predictor of it, valuable in assessing prediabetes, atherosclerosis, and other diseases. However, the validity of TyG-BMI in osteoporosis studies remains inadequate. PURPOSE: The purpose of this study was to evaluate the relationship between TyG-BMI and BMD as well as the effect of TyG-BMI on the odds of developing osteoporosis in US adults without diabetes. METHODS: National Health and Nutrition Examination Survey data were obtained. The relationship between TyG-BMI and BMD was evaluated via multivariate linear regression models. Smoothed curve fitting and threshold effect analysis explored potential non-linear relationships, and age, gender, and race subgroup analyses were performed. In addition, multivariate logistic regression models were employed to analyze its potential role in the development of osteoporosis. RESULTS: In a study of 6501 participants, we observed a significant positive correlation between the TyG-BMI index and BMD, even after adjusting for covariates and categorizing TyG-BMI. The study identified specific TyG-BMI folding points-112.476 for the total femur BMD, 100.66 for the femoral neck BMD, 107.291 for the intertrochanter BMD, and 116.58 for the trochanter BMD-indicating shifts in the relationship's strength at these thresholds. While the association's strength slightly decreased after the folding points, it remained significant. Subgroup analyses further confirmed the positive TyG-BMI and BMD correlation. Multivariate linear regression analyses indicated a lower osteoporosis risk in participants with higher TyG-BMI levels, particularly in menopausal women over 40 and men over 60. CONCLUSION: This study suggests a positive correlation between BMD and TyG-BMI in US adults without diabetes. Individuals with higher levels of TyG-BMI may have a lower risk of osteoporosis.

Statin-Associated Liver Dysfunction and Muscle Injury: epidemiology, Mechanisms, and Management Strategies.

Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases.

Regulatory role of BNP in the spinal center of rats with nonbacterial prostatitis.

BACKGROUND: A growing body of evidence has shown that activating spinal cord glial cells (typically astrocytes and microglial cells) is closely related to hyperpathia and persistent pain. OBJECTIVE: To investigate the expression of GFAP and CR3/CD11b in cornu dorsale medullae spinalis of rats with nonbacterial prostatitis, to explore the therapeutic efficacy and action mechanism of intrathecal injection of BNP alleviating chronic neuropathic pain. METHODS: Eighteen male SPF SD rats were randomly divided into sham operation control group, nonbacterial prostatitis group (NBP) and intrathecal injection BNP group, the NBP model was established by intraprostatic injection of CFA, and the spinal cord of L6-S1 segment was extracted seven days after intrathecal injection of BNP; The expression of GFAP and CR3/CD11b in dorsal horn of spinal cord were detected by immunofluorescence and Western blot. RESULTS: The cumulative optical density values of GFAP and CR3/CD11b immunofluorescence assay in the NBP group were higher than those in the sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.01); The expression of GFAP and CR3/CD11b in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.01). Western blot results showed that the expression of GFAP and CR3/CD11B in NBP group were higher than those in sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.05). The expression of GFAP and CR3/CD11B in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.05). CONCLUSION: Intrathecal injection of BNP can down-regulate the expressions of GFAP and CR3/CD11b in L6-S1 spinal cord of NBP rat model and to further inhibit chronic pain caused by NBP.

Westerlies-driven transboundary transport of atmospheric mercury to the north-central Tibetan Plateau.

The transboundary mercury (Hg) pollution has caused adverse effects on fragile ecosystems of the Tibetan Plateau (TP). Yet, knowledge of transport paths and source regions of atmospheric Hg on the inland TP remains poor. Continuous measurements of atmospheric total gaseous mercury (TGM) were conducted in the central TP (Tanggula station, 5100 m a.s.l., June-October). Atmospheric TGM level at Tanggula station (1.90 ± 0.30 ng m-3) was higher than the background level in the Northern Hemisphere. The identified high-potential source regions of atmospheric TGM were primarily located in the northern South Asia region. TGM concentrations were lower during the Indian summer monsoon (ISM)-dominant period (1.81 ± 0.25 ng m-3) than those of the westerly-receding period (2.18 ± 0.40 ng m-3) and westerly-intensifying period (1.91 ± 0.26 ng m-3), contrary to the seasonal pattern in southern TP. The distinct TGM minima during the ISM-dominant period indicated lesser importance of ISM-transported Hg to Tanggula station located in the northern boundary of ISM intrusion, compared to stations in proximity to South and Southeast Asia source regions. Instead, from the ISM-dominant period to the westerly-intensifying period, TGM concentrations showed an increasing trend as westerlies intensified, indicating the key role of westerlies in transboundary transport of atmospheric Hg to the inland TP.

Visible-light-induced C(sp3)-H bromination of 4-methylthiophene derivatives with HBr/H2O2.

A convenient method to synthesize ethyl 4-(bromomethyl)thiophene-3-carboxylate derivatives has been developed via a visible-light-induced radical process in good yields and with wide functional group tolerance under air conditions and at ambient temperature. The present protocol has the advantages of a high atom economy, easy purification, and environmental friendliness as it employs HBr as the bromine source and the cheap and low-toxic H2O2 as the oxidant. The synthetic utility of this method is demonstrated by a gram scale reaction and its application in the innovative synthesis of the clinical drug relugolix.

An effector SsCVNH promotes the virulence of Sclerotinia sclerotiorum through targeting class III peroxidase AtPRX71.

Many plant pathogens secrete effector proteins into the host plant to suppress host immunity and facilitate pathogen colonization. The necrotrophic pathogen Sclerotinia sclerotiorum causes severe plant diseases and results in enormous economic losses, in which secreted proteins play a crucial role. SsCVNH was previously reported as a secreted protein, and its expression is significantly upregulated at 3 h after inoculation on the host plant. Here, we further demonstrated that deletion of SsCVNH leads to attenuated virulence. Heterologous expression of SsCVNH in Arabidopsis enhanced pathogen infection, inhibited the host PAMP-triggered immunity (PTI) response and increased plant susceptibility to S. sclerotiorum. SsCVNH interacted with class III peroxidase AtPRX71, a positive regulator of innate immunity against plant pathogens. SsCVNH could also interact with other class III peroxidases, thus reducing peroxidase activity and suppressing plant immunity. Our results reveal a new infection strategy employed by S. sclerotiorum in which the fungus suppresses the function of class III peroxidases, the major component of PTI to promote its own infection.

The safety and feasibility Assessment of Overlap Esophagojejunostomy with Self-pulling and Latter Transection Technique in Totally Laparoscopic Total Gastrectomy.

BACKGROUND: This study presents an innovative technique in totally laparoscopic total gastrectomy (TLTG) for Overlap esophagojejunostomy, termed self-pulling and latter transection (Overlap SPLT). It evaluates the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end esophagojejunostomy incorporating self-pulling and latter transection (FETE SPLT). METHODS: From September 2018 to September 2023, this study enrolled 68 gastric cancer patients who underwent totally laparoscopic total gastrectomy (TLTG) with Overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathological characteristics, surgical and postoperative outcomes data for Overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for Overlap SPLT was 25.3 ± 7.4minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0minutes, P = 0.031). Perioperatively, one anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = 0.682). No statistically significant differences were found between the two groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs. 5.8%, P = 0.676). CONCLUSION: The Overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between Overlap SPLT and FETE SPLT, but Overlap SPLT costed one additional stapler cartridge and required a longer duration.

Convergent High O2 Affinity but Distinct ATP-Mediated Allosteric Regulation of Hemoglobins in Oviparous and Viviparous Eremias Lizards from the Qinghai-Tibet Plateau.

The functional adaptation and underlying molecular mechanisms of hemoglobins (Hbs) have primarily concentrated on mammals and birds, with few reports on reptiles. This study aimed to investigate the convergent and species-specific high-altitude adaptation mechanisms of Hbs in two Eremias lizards from the Qinghai-Tibet Plateau. The Hbs of high-altitude E. argus and E. multiocellata were characterized by significantly high overall and intrinsic Hb-O2 affinity compared to their low-altitude populations. Despite the similarly low Cl- sensitivities, the Hbs of high-altitude E. argus exhibited higher ATP sensitivity and ATP-dependent Bohr effects than that of E. multiocellata, which could facilitate O2 unloading in respiring tissues. Eremias lizards Hbs exhibited similarly low temperature sensitivities and relatively high Bohr effects at lower temperatures, which could help to stably deliver and release O2 to cold extremities at low temperatures. The oxygenation properties of Hbs in high-altitude populations might be attributed to varying ratios of ß2/ß1 globin and substitutions on the ß2-type globin. Notably, the Asn12Ala in lowland E. argus could cause localized destabilization of the E-helix in the tetrameric Hb by elimination of hydrogen bonds, thereby resulting in its lowest O2 affinity. This study provides a valuable reference for the high-altitude adaptation mechanisms of hemoglobins in reptiles.

Correction: Cao et al. Fluorinated PEG-PEI Coated Magnetic Nanoparticles for siRNA Delivery and CXCR4 Knockdown. Nanomaterials 2022, 12, 1692.

In the original publication [...].

IL-33 Enhances the Total Production of IgG, IgG1, and IgG3 in Angiostrongylus cantonensis-Infected Mice.

The purpose of this study is to clarify the role of IL-33 in the immune response to angiostrongyliasis, especially in terms of antibody production and isotype switching. In our experiment, C57BL/6 mice were each infected with 35 infectious larvae and were divided into groups that received an intraperitoneal injection of IL-33, anti-IL-33 monoclonal antibody (mAb), or anti-ST2 mAb 3 days post-infection (dpi) and were subsequently administered booster shots at 5-day intervals with the same dose. Serum samples from each group were collected weekly for ELISA assays. The levels of total IgG, IgG1, and IgG3 were significantly increased in A. cantonensis-infected mice that were treated with IL-33, and the levels decreased significantly in infected groups treated with anti-IL-33 or anti-ST2 mAb. These results suggest that IL-33 may play a critical role in the pathogenesis of human angiostrongyliasis and could be useful for understanding protective immunity against this parasitic infection.

OsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate.

The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

Multi-metal ions co-regulated vanadium oxide cathode toward long-life aqueous zinc-ion batteries.

Interlayer intercalation engineering shows great feasibility to improve the structure stability of the layered oxides. Although high Zn-storage capability has been attained based on the pillar effect of multifarious intercalants, an in-depth understanding the synergistic effect of intercalated multiple metal ions is still in deficiency. Herein, alkali metal ion K+, alkaline earth metal ion Mg2+ and trivalent metal ion Al3+ are introduced into the VO interlayer of V2O5. Due to the different electronegativity and hydrated ion radius of K+, Mg2+ and Al3+, adjusting the relative proportions of these metal ions can achieve an appropriate interlayer spacing, stable layer structure and regular morphology, which facilitates the transport kinetics of Zn2+. Under the synergistic effect of pre-intercalated multi-metal ion, the optimal tri-metal ion intercalated hydrated V2O5 cathode exhibits a high specific capacity of 382.4 mAh g-1 at 0.5 A g-1, and long-term cycling stability with capacity retention of 86 % after 2000 cycles at the high current density of 10 A g-1. Ex-situ and kinetic characterizations reveal the fast charge transfer and reversible Zn2+ intercalation mechanism. The multi-ion engineering strategy provides an effective way to design desirable layered cathode materials for aqueous zinc-ion batteries.

Concentration properties of biopolymers via dead-end forward osmosis.

Extracellular polymeric substances (EPSs) in excess sludge of wastewater treatment plants are valuable biopolymers that can act as recovery materials. However, effectively concentrating EPSs consumes a significant amount of energy. This study employed novel energy-saving pressure-free dead-end forward osmosis (DEFO) technology to concentrate various biopolymers, including EPSs and model biopolymers [sodium alginate (SA), bovine serum albumin (BSA), and a mixture of both (denoted as BSA-SA)]. The feasibility of the DEFO technology was proven and the largest concentration ratios for these biopolymers were 94.8 % for EPSs, 97.1 % for SA, 97.8 % for BSA, and 98.4 % for BSA-SA solutions. An evaluation model was proposed, incorporating the FO membrane's water permeability coefficient and the concentrated substances' osmotic resistance, to describe biopolymers' concentration properties. Irrespective of biopolymer type, the water permeability coefficient decreased with increasing osmotic pressure, remained constant with increasing feed solution (FS) concentration, increased with increasing crossing velocity in the draw side, and showed little dependence on draw salt type. In the EPS DEFO concentration process, osmotic resistance was minimally impacted by osmotic pressure, FS concentration, and crossing velocity, and monovalent metal salts were proposed as draw solutes. The interaction between reverse diffusion metal cations and EPSs affected the structure of the concentrated substances on the FO membrane, thus changing the osmotic resistance in the DEFO process. These findings offer insights into the efficient concentration of biopolymers using DEFO.

Dynamic radiological features predict pathological response after neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant immunochemotherapy (NICT) plus esophagectomy has emerged as a promising treatment option for locally advanced esophageal squamous cell carcinoma (LA-ESCC). Pathologic complete response (pCR) is a key indicator associated with great efficacy and overall survival (OS). However, there are insufficient indicators for the reliable assessment of pCR. METHODS: 192 patients with LA-ESCC treated with NICT from December 2019 to October 2023 were recruited. According to pCR status, patients were categorized into pCR group (22.92%) and non-pCR group (77.08%). Radiological features of pretreatment and preoperative CT images were extracted. Logistic and COX regressions were trained to predict pathological response and prognosis, respectively. RESULTS: Four of the selected radiological features were combined to construct an ESCC preoperative imaging score (ECPI-Score). Logistic models revealed independent associations of ECPI-Score and vascular sign with pCR, with AUC of 0.918 in the training set and 0.862 in the validation set, respectively. After grouping by ECPI-Score, a higher proportion of pCR was observed among the high-ECPI group and negative vascular sign. Kaplan Meier analysis demonstrated that recurrence-free survival (RFS) with negative vascular sign was significantly better than those with positive (P = 0.038), but not for OS (P = 0.310). CONCLUSIONS: This study demonstrates dynamic radiological features are independent predictors of pCR for LA-ESCC treated with NICT. It will guide clinicians to make accurate treatment plans.

The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice.

Polycystic ovary syndrome (PCOS), an endocrine disorder afflicting 6-20% of women of reproductive age globally, has been linked to alterations in the gut microbiome. We previously showed that in PCOS, elevation of Bacteroides vulgatus in the gut microbiome was associated with altered bile acid metabolism. Here we show that B. vulgatus also induces a PCOS-like phenotype in female mice via an alternate mechanism independent of bile acids. We find that B. vulgatus contributes to PCOS-like symptoms through its metabolite agmatine, which is derived from arginine by arginine decarboxylase. Mechanistically, agmatine activates the farnesoid X receptor (FXR) pathway to subsequently inhibit glucagon-like peptide-1 (GLP-1) secretion by L cells, which leads to insulin resistance and ovarian dysfunction. Critically, the GLP-1 receptor agonist liraglutide and the arginine decarboxylase inhibitor difluoromethylarginine ameliorate ovarian dysfunction in a PCOS-like mouse model. These findings reveal that agmatine-FXR-GLP-1 signalling contributes to ovarian dysfunction, presenting a potential therapeutic target for PCOS management.

Continuous renal Surface Cooling Technique (CSCT) in robotic assisted kidney transplantation: technique and outcomes from a high-volume center, a prospective cohort study.

BACKGROUND: Robot-assisted kidney transplantation (RAKT) surgery is an advanced minimally invasive technique, albeit with extended surgical and kidney ischemia time. To safeguard kidney function, we have devised a continuous surface cooling method (CSCT) for intraoperative kidney cooling. MATERIALS AND METHODS: Patients receiving RAKT were divided into CSCT group and conventional group. The CSCT is a custom-designed apparatus composed of a single-layer plastic bag, featuring an inflow and an outflow that create a closed circuit for the continuous flow of cooling saline. The conventional group utilized ice slush for kidney graft cooling (Vattikuti Urology Institute-Medanta Technique, VUIMT). Patients who underwent open renal transplantation during the same period were also included in the study. All patients were subject to a minimum 2-month follow-up. And 1:3 propensity score matching was used to minimize selection bias. RESULTS: A total of 144 patients underwent CSCT, 47 underwent VUIMT, and 196 underwent open surgery were included in the study, while after matching, 129, 43, 129 patients were included in the three groups, respectively. The median follow-up time was 19 months. None of the patients experienced delayed graft function, patient mortality, or graft loss. After introducing the kidney into the abdominal cavity for 20 minutes, the surface temperature of the kidney in the CSCT group was notably lower compared to the VUIMT group (15.42±0.88 vs. 21.74±2.53°C, P=0.001). This temperature disparity became more pronounced at 65 minutes (19.74±1.61 vs. 29.82±1.63°C, P<0.001). At both 3 and 7 days post-transplantation, creatinine levels in the VUIMT group were significantly higher than those in the CSCT and open surgery groups (at 3 d, 244.13±45.61 vs. 182.51±55.47 in CSCT group, P<0.001, or vs. 182.77±61.32 in the open surgery group, P<0.001; at 7 d, 162.42±54.86 vs. 143.11±44.32 in the CSCT group, P<0.001, or vs. 135.23±45.27 in the open surgery group, P<0.001). No differences were observed in blood creatinine, estimated glomerular filtration rate, and perioperative complications between the CSCT and open surgery groups. CONCLUSION: The CSCT presents a significant advantage over the traditional VUIMT method in terms of kidney cooling and early postoperative kidney function preservation. Additional research is required to ascertain whether the CSCT can enhance the long-term prognosis of kidney transplant recipients.

Rational Design of Local Reaction Environment for Electrocatalytic Conversion of CO2 into Multicarbon Products.

The electrocatalytic conversion of CO2 into multi-carbon (C2+) products provides an attractive route for storing intermittent renewable electricity as fuels and feedstocks with high energy densities. Although substantial progress has been made in selective electrosynthesis of C2+ products via engineering the catalyst, rational design of the local reaction environment in the vicinity of catalyst surface also acts as an effective approach for further enhancing the performance. Here, we discuss recent advances and pertinent challenges in the modulation of local reaction environment, encompassing local pH, the choice of the species and concentrations of cations and anions as well as local reactant/intermediate concentrations, for achieving high C2+ selectivity. In addition, mechanistic understanding in the effects of the local reaction environment is also discussed. Particularly, the important progress extracted from in situ and operando spectroscopy techniques provides insights into how local reaction environment affects C-C coupling and key intermediates formation that lead to reaction pathways toward a desired C2+ product. The possible future direction in understanding and engineering the local reaction environment is also provided.