Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.

OBJECTIVES: The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. DESIGN: We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. SETTING: Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. PATIENTS: Adult patients presenting to the emergency department with severe sepsis or septic shock. INTERVENTIONS: EGDT vs. usual care. MEASUREMENTS AND MAIN RESULTS: A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. CONCLUSIONS: Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.

Effects of Clausena lansium leaves volatile oil emulsion against Staphylococcus aureus in mice via autophagy modulation.

BACKGROUND: Volatile oil from fresh Clausena lansium (Lour.) Skeels (Rutaceae) (common name Wampee) has been previously extracted by our group from fresh C. lansium leaf and its components were qualitative and quantitatively analyzed by GC-MS. It altered the cell membrane permeability of Staphylococcus aureus and reduced the levels of inflammation factors. However, previous in vivo reports on the anti-inflammatory and the antibacterial properties against S. aureus are scarce. HYPOTHESIS/PURPOSE: To evaluate the protective in vivo effects of Wampee leaves volatile oil emulsion (WVOE) against S. aureus-induced pneumonia and elucidate the underlying mechanisms of action. METHODS: Wild-type and nucleotide oligomerization domain-like receptor protein 3 (NLRP3)-deficient mice were used. Mice were treated with WVOE for 7 days, and subjected to S. aureus infection by nasal administration on day 5 for 48 h. Lung and blood samples were collected for assessing lung damage and protein abundance. Lung bacterial load, wet/dry ratio, C-reactive protein (CRP) levels, inflammatory cytokines secretion, and lung histopathological injury were examined. RESULTS: WVOE effectively reduced lung bacterial load, wet/dry ratio, and CRP levels increased following S. aureus infection in mice. WVOE decreased the secretion of inflammatory cytokines (IL-6 and TNF-α) and lung histopathological injury, and suppressed the NF-κB pathway and NLRP3 inflammasome activation. NLRP3-/- mice exhibited lower bacterial load, inflammatory cytokines levels and lung histopathological injury compared with mice in the model group. Autophagy was enhanced in S. aureus-infected mice, with higher levels of p-mTOR, Beclin-1, Atg 16L1, Atg7, p62, p-p62, and LC3II. WVOE administration restored the autophagy related protein levels. Autophagy was inhibited in NLRP3-/- mice of the control and model groups, and WVOE lost its ability to regulate the autophagy-related proteins enhanced upon S. aureus infection. WVOE enhanced autophagy to alleviate lung injury by inhibiting NLRP3-targeted P62. Furthermore, compared with the 3MA + model group, WVOE reduced the bacterial load and CRP levels, pulmonary septa narrowing, and congestion. NLRP3 protein expression increased due to autophagy inhibition. WVOE exerted a pharmacological effect through the PI3K/AKT/mTOR pathway. CONCLUSION: WVOE regulated the PI3K/AKT/mTOR pathway and enhanced autophagy, with NLRP3 playing a crucial role. WVOE exhibited protective effects against S. aureus-induced pneumonia by inhibiting NLRP3 inflammasome activation and enhancing autophagy. These findings expand the understanding of antibacterial properties of WVOE, and provide novel insights into the therapeutic potential of WVOE in managing S. aureus infections.

Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A modification is the most common post-transcriptional modification of eukaryotic mRNA, accounting for 80% of RNA methylation modifications. At the same time, several other modifications of RNA, such as N1-methyladenosine (m1A), 5-methylcytosine (m5C), 3-methylcytosine (m3C), pseudouridine (Ψ) and N7-methylguanosine (m7G) have also been demonstrated to be involved in cancer and drug resistance. This review mainly discusses the research progress of RNA modifications in the field of cancer and drug resistance and targeting of m6A regulators by small molecule modulators, providing reference for future study and development of combination therapy to reverse cancer drug resistance.

Exploring the therapeutic potential of "Tianyu" medicine pair in rheumatoid arthritis: an integrated study combining LC-MS/MS, bioinformatics, network pharmacology, and experimental validation.

Background: Rheumatoid arthritis (RA) is a widespread chronic autoimmune disease that primarily causes joint inflammation and damage. In advanced stages, RA can result in joint deformities and loss of function, severely impacting patients' quality of life. The "Tianyu" pair (TYP) is a traditional Chinese medicine formulation developed from clinical experience and has shown some effectiveness in treating RA. However, its role in the complex biological mechanisms underlying RA remains unclear and warrants further investigation. Methods: We obtained gene sequencing data of synovial tissues from both RA patients and healthy individuals using two gene microarrays, GSE77298 and GSE55235, from the GEO database. Through an integrated approach involving bioinformatics, machine learning, and network pharmacology, we identified the core molecular targets of the "Tianyu" medicine pair (TYP) for RA treatment. Liquid chromatography-mass spectrometry was then employed to analyze the chemical components of TYP. To validate our findings, we conducted animal experiments with Wistar rats, comparing histopathological and key gene expression changes before and after TYP treatment. Results: Our data analysis suggests that the onset of RA may be associated with inflammation-related immune cells involved in both adaptive and innate immune responses. Potential key targets for TYP treatment in RA include AKR1B10, MMP13, FABP4, NCF1, SPP1, COL1A1, and RASGRP1. Among the components of TYP, Kaempferol, Quercetin, and Salidroside were identified as key, with MMP13 and NCF1 showing the strongest binding affinity to these compounds. Animal experiments confirmed the findings from bioinformatics and network pharmacology, validating the key targets and therapeutic effects of TYP in treating RA. Conclusion: Our study reveals that TYP has potential clinical value in the treatment of rheumatoid arthritis. This research enhances our understanding of RA's pathogenesis and provides insight into potential therapeutic mechanisms.

RNA sequencing and functional analysis uncover key long non-coding RNAs involved in regulating pollen fertility during the process of gametocidal action in wheat.

Gametocidal (Gc) chromosomes have been widely utilized in genetic breeding due to their ability to induce chromosomal breakage and eliminate gametes that lack them. Long noncoding RNAs (lncRNAs) have various functional mechanisms in regulating pollen and anther development; however, their regulatory contributions to Gc action are still unknown. Here, we identified 2824 differentially expressed lncRNAs (DE-lncRNAs) from the anther tissues of Triticum aestivum cv. Chinese Spring (CS) and Chinese Spring-Gc 3C chromosome monosomic addition line (CS-3C) through sequencing. In this study, we predicted 161 target mRNAs for 145 DE-lncRNAs, including 104 cis-regulatory, 60 trans-regulatory, and three both cis-regulatory and trans-regulatory manner. Combined with our previous miRNA sequencing data, 241 DE-lncRNAs functioned as potential endogenous target mimics (eTMs) for 84 differentially expressed microRNAs (DE-miRNAs, including 12 novel miRNAs). The results of transient transformation in tobacco leaves indicated that L006278 could bind to MTCONS_00006277, which encoded a calcineurin CBL-interacting protein kinase 19-like, and suppress its expression. Furthermore, L117735 could function as an eTM for tae-miR9657b-3p, and L056972 could function as an eTM for gc-m2240-5p. To explore the function of lncRNAs in the process of Gc action, we transformed L006278, an up-regulated lncRNA in CS-3C, into rice to analyze its effect on pollen fertility. Overexpression of L006278 led to a reduction in rice pollen fertility. Overall, our findings indicate that lncRNAs can contribute to the regulation of pollen fertility during the process of Gc action by regulating the expression levels of target mRNAs and acting as eTMs for certain key miRNAs.

Design and development of a series of 4-(piperazin-1-yl)pyrimidines as irreversible menin inhibitors.

The interaction between menin and MLL1 protein plays an important role in AML with MLL rearrangement and NPM1 mutation. Blocking the formation of menin-MLL complex can inhibit proliferation and induce differentiation in these cancer subtypes. In development of anticancer drugs, irreversible inhibitors are gaining spotlight as they may have better activities than the reversible analogs. Therefore, we designed and developed a novel series of covalent menin inhibitors. Among these compounds, 37 emerges as a selective and potent inhibitor of MLL fusion protein-expressing leukemic cells. The cellular study indicates 37 has a distinct mechanism of action, in both reducing menin protein levels and downregulating MEN1 transcription. This effect of 37 is not involved in proteasomal degradation, and may directly affect the synthesis of menin protein, which offers a significant advantage in addressing acquired resistance to menin inhibitors. Further study showed that compound 37 has prolonged anti-leukemic action and exhibits promising in vivo efficacy, making it a valuable probe for further menin-MLL interaction studies.

Why is pollen in Camellia oleifera inedible to honeybees?

This Commentary examines a recent study that addressed a long-standing controversy: Is the lethal effect of Tea-oil Camellia on honeybee larvae due to nectar or pollen toxicity? Flowers of Camellia oleifera are adapting to bird pollination, evolving 'anti-bee' traits such as theasaponin-containing pollen, which is toxic to bee larvae.

Structure regulation of oxidized soybean cellulose nanocrystals/poly-acrylamide hydrogel and its application potential in wound dressing.

The development of functional dressings based on natural polysaccharide-based hydrogels remains a great challenge, and the specific roles of gel composition and drug-controlled release mechanisms were unclear. In this study, oxidized soybean cellulose nanocrystals (CNCs)/poly-acrylamide (PAM) hydrogel was prepared. The proportion of CNCs, crosslinkers, and water in the system was regulated to fine-tune the rheological performances, texture properties, transparency, and micro-network structures of CNCs/PAM hydrogel, and further explored its application potential in the field of wound dressings. It was found that CNCs improved the rigidity and adhesion of hydrogels, crosslinkers improved the network density, and water promoted the softening and fluidity of hydrogels. The effective filling of CNCs in the composite hydrogel was verified by FTIR, XRD, and NMR. Furthermore, the pH responsiveness and drug-loading potential of the smart hydrogel were tested by swelling and drug-controlled release experiments, elucidating drug-release dynamic mechanisms during the wound healing process. The inhibition zones (>7 mm) of gram-positive/negative bacteria and cell viability (>100 %) assay showed satisfactory biocompatibility, as the hydrogel effectively accelerated wound healing in a wound model. These results elucidated the regulation mechanism of the structures of CNCs/PAM hydrogel and revealed the application potential of CNCs/PAM hydrogel in wound dressings.

Interpreting the complexities of the plastid genome in dinoflagellates: a mini-review of recent advances.

Photosynthetic dinoflagellates play crucial roles in global primary production and carbon fixation. Despite their success in filling various ecological niches, numerous mysteries about their plastid evolution and plastid genomes remain unsolved. The plastid genome of dinoflagellates presents one of the most complex lineages in the biological realm, mainly due to multiple endosymbiotic plastid events in their evolutionary history. Peridinin-containing dinoflagellates possess the most reduced and fragmented genome, with only a few genes located on multiple "minicircles", whereas replacement plastids in dinoflagellate lineages have undergone different degrees of endosymbiotic gene transfer. Recent advancements in high-throughput sequencing have improved our understanding of plastid genomes and plastid-encoded gene expression in many dinoflagellate species. Plastid transcripts of dinoflagellates exhibit two unconventional processing pathways: the addition of a 3' poly(U) tail and substitutional RNA editing. These pathways are widely employed across dinoflagellate lineages, which are possibly retained from the ancestral peridinin plastid. This mini-review summarizes the developments in the plastid genomes of dinoflagellates and pinpoints the research areas that necessitate further exploration, aiming to provide valuable insights into plastid evolution in these fascinating and important organisms.

Two-Pronged Attack: Dual Activation of Fat Reduction Using Near-Infrared-Responsive Nanosandwich for Targeted Anti-Obesity Treatment.

Excessive fat accumulation and chronic inflammation are two typical characteristics of obesity. AMP-activated protein kinase (AMPK), a master regulator of energy metabolism, is involved in adipogenesis, lipogenesis, and inflammation modulation in adipose tissue (AT). Thus, effective lipid reduction and anti-inflammation through AMPK regulation play vital roles in treating obesity. Herein, an anti-obesity nanosandwich is fabricated through attaching polymetformin (PolyMet) onto photothermal agent black phosphorus nanosheets (BP). PolyMet activates AMPK to inhibit adipogenesis, promote browning, and mitigate AT inflammation by decreasing macrophage infiltration, repolarizing macrophage phenotype, and downregulating pro-inflammatory cytokines. Additionally, BP induces lipolysis and apoptosis of adipocytes and macrophages through a photothermal effect. By further functionalization using hyaluronic acid (HA) and MMP2 substrate-linking P3 peptide-modified HA (P3-HA), an enhanced anti-obesity effect is obtained by dual-targeting of P3 and HA, and HA-mediated CD44 poly-clustering after MMP2 cleavage. Upon laser irradiation, the designed nanosandwich (P3-HA/PM@BP) effectively inhibits obesity development in obese mice, increases M2/M1 ratio in AT, reduces the serum levels of cholesterol/triglyceride and improves insulin sensitivity, exhibiting promising research potential to facilitate the clinical development of modern anti-obesity therapies.

Stability evaluation method of gasification coal pillar under thermal coupling condition for prevention of environment secondary pollution.

The instability of gasification coal pillars can easily induce the further development of water-conducting fractures, which leads to the connection of gasification combustion space and aquifer, and then causes groundwater pollution. Therefore, it is crucial to assess the stability of gasification coal pillar to forestall the potential risk of environmental contamination resulting from underground coal gasification. In this paper, based on the shape of the combustion space area of underground coal gasification, considering the influence of the mechanical properties of the coal pillar and the temperature field under the condition of thermal coupling, the calculation method of the yield zone width of gasification coal pillar is proposed. Considering the destabilizing factors affecting the coal pillar and the relationship between actual and ultimate bearing capacities after stripping and yielding, a stability evaluation method for the 'hyperbolic' coal pillar is proposed. Additionally, the effects of various factors on the stripping, yielding, and safety factor of the coal pillar are analyzed. The new method was applied to the Ulanqab underground coal gasification test site, which proved its effectiveness. The research results are of great practical significance for designing underground coal gasification production and preventing environmental pollution.

Colloid mobilization and transport in response to freeze-thaw cycles: Insights into the heavy metal(loid)s migration at a smelting site.

Smelting sites often exhibit significant heavy metal(loid)s (HMs) contamination in the soil and groundwater, which are inevitably subjected to environmental disturbances. However, there is limited information available regarding the migration behaviors of HMs in a disturbed scenario. Thus, this work explored the migration of HMs-bearing colloids in response to freeze-thaw treatments by laboratory simulation and pore-scale study. Ultrafiltration results of soil effluents revealed that 61.5 %, 47.6 %, 68.0 %, and 59.2 % of Zn, Cd, Pb, and As were present in colloidal phase, and co-transported during treatments. Nanoparticle tracking analysis (NTA) further confirmed that freeze-thaw cycles were conducive to the generation of colloidal particles and showed the heteroagglomeration among different particles. Pore-network model (PNM) was used to quantify the soil macropore characteristics (macropore diameter, macropore number, coordination number, and Euler value) after treatments. It is evident that freeze-thaw cycles induced the formation of larger macropores while simultaneously enhancing macropore connectivity, thereby establishing an optimal pathway for colloid migration. These findings underscored the importance of environmental disturbances as a trigger for the release and migration of HMs in the smelting site, offering valuable insights for controlling HMs pollution. ENVIRONMENTAL IMPLICATION: The contaminated site has been subjected to prolonged environmental disturbances, causing the exacerbation of pollutants leaching and frequent occurrences of unstable pollution situations. This work explored the migration of HMs-bearing colloids in response to freeze-thaw treatments by laboratory simulation and pore-scale study. The distinct effects of freeze-thaw treatment on colloidal particle number concentration and macropore characteristics may explain the generation and migration of colloid-associated HMs driven by environmental disturbances. This work revealed the underlying mechanisms driving the redistribution of HMs under freeze-thaw cycles, offering valuable insights for risk assessment of soil and groundwater associated with HMs migration.

NT-pro-BNP Level is Related to Left Ventricular Remodeling in Patients With Primary Aldosteronism.

AIMS: To assess the relationship between the left ventricular remodeling parameters of cardiac magnetic resonance and NT-pro-BNP in patients with primary aldosteronism (PA). METHODS: Seventy-four PA and 39 essential hypertension patients were prospectively recruited and underwent cardiac magnetic resonance. Plasma NT-pro-BNP was measured before patients underwent cardiac magnetic resonance. Left ventricular remodeling parameters were defined as left ventricular function parameters, T1 mapping parameters, and strain parameters. Differences in continuous variables between two groups were analyzed using Student's t-test or Mann-Whitney U test. Differences in categorical variables between two groups were analyzed by chi-squared test. Spearman's correlation and linear regression were used to analyze the relationships between left ventricular remodeling parameters and plasma NT-Pro-BNP level. P<0.05 was considered as statistically significant. RESULTS: Patients with PA demonstrated higher NT-pro-BNP [86.0 (49.5, 145.5) vs. 45.0 (28.5, 73.5) pg/mL, P=0.001] and Native T1 (1227±41 vs. 1206±43 ms, P=0.015) level than essential hypertension patients. Compared to patients with normal NT-pro-BNP levels, those with abnormal levels demonstrated different left ventricular remodeling parameters. NT-pro-BNP level was independently related to native T1 (ß=0.316, P=0.006), extracellular volume (ß=0.419, P<0.001), short-axis global circumferential strain (ß=0.429, P<0.001), four-chamber global longitudinal strain (ß=0.332, P=0.002), and four-chamber global radial strain (ß=-0.334, P=0.004) in patients after adjusting for baseline characteristics. CONCLUSIONS: NT-pro-BNP level was related to left ventricular remodeling parameters derived from cardiac magnetic resonance in patients with PA. This result implies that clinicians should pay attention to NT-pro-BNP assessment in patients with PA in routine clinical assessment.

Exploring the dynamics of sports records evolution through the gembris prediction model and network relevance analysis.

BACKGROUND: Sports records hold valuable insights into human physiological limits. However, presently, there is a lack of integration and evolutionary patterns in the recorded information across various sports. METHODS: We selected sports records from 1992 to 2018, covering 24 events in men's track, field, and swimming. The Gembris prediction model calculated performance randomness, and Pearson correlation analysis assessed network relevance between projects. Quantitative study of model parameters revealed the impact of various world records' change range, predicted value, and network correlation on evolutionary patterns. RESULTS: 1) The evolution range indicates that swimming events generally have a larger annual world record variation than track and field events; 2) Gembris's predictions show that sprint, marathon, and swimming records outperform their predicted values annually; 3) Network relevance analysis reveals highly significant correlations between all swimming events and sprints, as well as significant correlations between marathon and all swimming events. CONCLUSION: Sports record evolution is closely linked not only to specific sports technology but also to energy expenditure. Strengthening basic physical training is recommended to enhance sports performance.

[Research progress on anti-swelling hydrogels in biomedical field].

Hydrogel is a kind of degradable hydrophilic polymer, but excessive hydrophilicity leads to larger volume, lower elastic modulus and looser structure, which further affect its use. Especially in the field of biomedical engineering, excessive swelling of the hydrogel can compress the nerves and improve degradation rate resulting in mismatch of tissue growth and released ions. Therefore, anti-swelling hydrogel has been a research hotspot in recent years. This paper reviews the recent research progress on anti-swelling hydrogel, and expounds the application mechanism and preparation method of hydrogel in biomedical engineering, aiming to provide some references for researchers in the field of anti-swelling hydrogel.

VaxBot-HPV: A GPT-based Chatbot for Answering HPV Vaccine-related Questions.

Background: HPV vaccine is an effective measure to prevent and control the diseases caused by Human Papillomavirus (HPV). This study addresses the development of VaxBot-HPV, a chatbot aimed at improving health literacy and promoting vaccination uptake by providing information and answering questions about the HPV vaccine. Methods: We constructed the knowledge base (KB) for VaxBot-HPV, which consists of 451 documents from biomedical literature and web sources on the HPV vaccine. We extracted 202 question-answer pairs from the KB and 39 questions generated by GPT-4 for training and testing purposes. To comprehensively understand the capabilities and potential of GPT-based chatbots, three models were involved in this study : GPT-3.5, VaxBot-HPV, and GPT-4. The evaluation criteria included answer relevancy and faithfulness. Results: VaxBot-HPV demonstrated superior performance in answer relevancy and faithfulness compared to baselines (Answer relevancy: 0.85; Faithfulness: 0.97) for the test questions in KB, (Answer relevancy: 0.85; Faithfulness: 0.96) for GPT generated questions. Conclusions: This study underscores the importance of leveraging advanced language models and fine-tuning techniques in the development of chatbots for healthcare applications, with implications for improving medical education and public health communication.

Recent Advances in Structure Design and Application of Metal Halide Perovskite-Based Gas Sensor.

Metal halide perovskites (MHPs) are emerging gas-sensing materials and have attracted considerable attention in gas sensors due to their unique bandgap structure and tunable optoelectronic properties. The past decade has witnessed significant developments in the gas-sensing field; however, their intrinsic structural instability and ambiguous gas-sensing mechanisms hamper their practical applications. Herein, we summarize the recent advances in MHP-based gas sensors. The physicochemical properties of MHPs are discussed at first. The structure design, including dimension design and engineering design, is overviewed as well as their fabrication methods, and we put forward our insights into the gas-sensing mechanism of MHPs. It is believed that enhanced understanding of gas-sensing mechanisms of MHPs are helpful for their application as gas-sensing materials, and structure design can enhance their stability, sensing sensitivity, and selectivity to target gases as gas sensors. Subsequently, the latest developments in MHP-based gas sensors are summarized according to their different application scenarios. Finally, we conclude with the current status and challenges in this field and propose future perspectives.

Photo-Induced Ultrafast Charge Transfer and Air-Stable Radical Formation in Tetraphenylpyrene Derivatives.

Stable organic radicals generated by photo-excitation hold applications in molecular switching devices and information storage. It remains challenging to develop photo-generated radical materials with rapid response and air stability in the solid state. Here, we report a structure based on 1,3,6,8-tetraphenylpyrene derivative (Py-TTAc) displaying photo-induced radicals with air stability in the solid state. Photo-induced electron transfer, exposed to a 365 nm ultraviolet lamp for 1 minute, affords radicals in Py-TTAc powder as confirmed by electron paramagnetic resonance (EPR) spectroscopy. The maximum radical concentration reaches 2.21 % after continuous irradiation for 1 hour and recurs more than 10 times without any chemical degradation. The mechanistic study according to the femtosecond transient absorption (fsTA) and X-ray technology suggests that the radicals are derived from photo-induced symmetry-breaking charge separation (SB-CS) and stabilized through non-covalent interactions. The photo-generated stable radical system is employed in anti-counterfeiting paper and optoelectronic device applications. This study will provide insights into the development of photoactive organic radical materials.

Transition-Metal-Free Radical Relay Cascade Annulation of Amides: Access to Antitumor Active Benzo[b]azepine and Oxindole Derivatives.

Efficient transition-metal-free synthesis of benzo[b]azepines and oxindoles is achieved via a radical relay cascade strategy employing halogen atom transfer (XAT) for aryl radical generation followed by intramolecular hydrogen atom transfer (HAT). Optimization yielded moderate to substantial yields under visible light irradiation. Preliminary biological assessments revealed promising anti-tumor activity for select compounds. This study underscores the potential of XAT-mediated radical relay cascades in medicinal chemistry and anticancer drug discovery.

Continuous adductor canal block versus continuous femoral nerve block for postoperative pain in patients undergoing knee arthroplasty: An updated meta-analysis of randomized controlled trials.

Continuous adductor canal block (CACB) is almost a pure sensory nerve block and can provide effective analgesia without blocking the motor branch of the femoral nerve. Thus, the objective of this study was to systematically evaluate the efficacy of CACB versus continuous femoral nerve block (CFNB) on analgesia and functional activities in patients undergoing knee arthroplasty. PubMed, Embase and the Cochrane Central Register of Controlled Trials (from inception to 3 October 2023) were searched for randomized controlled trials (RCTs) that compared CACB with CFNB in patients undergoing knee arthroplasty. Registration in the PROSPERO International prospective register of the meta-analysis was completed, prior to initiation of the study (registration number: CRD42022363756). Two independent reviewers selected the studies, extracted data and evaluated risk of bias by quality assessment. Revman 5.4 software was used for meta-analysis and the summary effect measure were calculated by mean differences and 95% confidence intervals. Eleven studies with a total of 748 patients were finally included. Pooled analysis suggested that both CACB and CFNB showed the same degree of pain relief at rest and at motion at 12 h, 24 h and 48 h in patients undergoing knee arthroplasty. Compared with CFNB, CACB preserved the quadriceps muscle strength better (P<0.05) and significantly shortened the discharge readiness time (P<0.05). In addition, there was no significant difference in opioid consumption, knee extension and flexion, timed up and go (TUG) test, or risk of falls between the two groups. Thus, Compared with CFNB, CACB has similar effects on pain relief both at rest and at motion and opioid consumption for patients undergoing knee arthroplasty, while CACB is better than CFNB in preserving quadriceps muscle strength and shortening the discharge readiness time.