Cu/Gd co-doped hydroxyapatite/poly lactic-co-glycolic acid composites enhance MRI imaging and bone defect regeneration.

Background: The hydroxyapatite (HA)/poly(lactide-co-glycolide) acid (PLGA) composite material is a widely used orthopedic implant due to its excellent biocompatibility and plasticity. Recent advancements in cation doping have expanded its potential biological applications. However, conventional HA/PLGA composites are not visible under X-rays post-implantation and have limited osteogenic induction capabilities. Copper (Cu) is known to regulate osteoblast proliferation and differentiation, while gadolinium (Gd) can significantly enhance the magnetic resonance imaging (MRI) capabilities of materials. Methods: This study aimed to investigate whether incorporating Cu and Gd into an HA/PLGA composite could enhance the osteogenic properties, in vivo bone defect repair, and MRI characteristics. We prepared a Cu/Gd@HA/PLGA composite and assessed its performance. Results: Material characterization confirmed that Cu/Gd@HA retained the morphology and crystal structure of HA. The Cu/Gd@HA/PLGA composite exhibited excellent nuclear magnetic imaging capabilities, porosity, and hydrophilicity, which are conducive to cell adhesion and implant detection. In vitro experiments demonstrated that the Cu/Gd@HA/PLGA composite enhanced the proliferation, differentiation, and adhesion of MC3T3-E1 cells, and upregulated COL-1 and BMP-2 expression at both gene and protein levels. In vivo studies showed that the Cu/Gd@HA/PLGA composite maintained strong T1-weighted MRI signals and significantly improved the bone defect healing rate in rats. Conclusion: These findings indicate that the Cu/Gd@HA/PLGA composites significantly enhance T1-weighted MRI capabilities, promote osteoblast proliferation and differentiation in vitro, and accelerate bone defect healing in vivo.

App review driven collaborative bug finding.

Software development teams generally welcome any effort to expose bugs in their code base. In this work, we build on the hypothesis that mobile apps from the same category (e.g., two web browser apps) may be affected by similar bugs in their evolution process. It is therefore possible to transfer the experience of one historical app to quickly find bugs in its new counterparts. This has been referred to as collaborative bug finding in the literature. Our novelty is that we guide the bug finding process by considering that existing bugs have been hinted within app reviews. Concretely, we design the BugRMSys approach to recommend bug reports for a target app by matching historical bug reports from apps in the same category with user app reviews of the target app. We experimentally show that this approach enables us to quickly expose and report dozens of bugs for targeted apps such as Brave (web browser app). BugRMSys 's implementation relies on DistilBERT to produce natural language text embeddings. Our pipeline considers similarities between bug reports and app reviews to identify relevant bugs. We then focus on the app review as well as potential reproduction steps in the historical bug report (from a same-category app) to reproduce the bugs. Overall, after applying BugRMSys to six popular apps, we were able to identify, reproduce and report 20 new bugs: among these, 9 reports have been already triaged, 6 were confirmed, and 4 have been fixed by official development teams.

Fluoropolymer-Gadolinium(III) Hybrids for Photoactivatable Dual-Mode T1-Weighted 1H MRI and 19F MRI Contrast Agents.

Multimodal imaging probes play a crucial role in overcoming the limitations associated with single-mode imaging for clinical medical diagnosis. This study focuses on the development of a photoresponsive fluorine-containing water-soluble polymer (PF) through RAFT polymerization. Subsequently, a polymer-gadolinium(III) hybrid (PF-Gd) dual-modal probe capable of T1-weighted 1H MRI and 19F MRI was synthesized via postmodification of PF with a Gd-DOTA derivative. Under physiological conditions (pH = 7.4), the hybrids exhibit UV-activated 19F NMR/MRI and enhanced 1H MRI. The inclusion of Gd3+ facilitates the acceleration of water molecule T1 relaxation, leading to high-intensity 1H MRI contrast. Leveraging the paramagnetic relaxation enhancement (PRE) effect between fluorine atoms and Gd3+, the restoration of Gd3+-accelerated 19F T2 relaxation enables precise photoactivation of 19F MRI signals, transitioning from the "OFF" to the "ON" state. This study provides an important reference for the development of hybrid systems that function as real-time diagnostic tools and offers controlled activation for multimodal imaging probes.

Heat-Excitation-Based Triboelectric Charge Promotion Strategy.

The surface charge decay is observed at high temperatures due to thermionic emission, which, however, may not be the only mechanism contributing to the surface charge variation. Here, a triboelectric charge promotion strategy due to the heat-excitation effect of hot electrons near the fermi level is demonstrated, while the final charge is determined by the balance between thermionic emission and the heat-excitation effect. It is demonstrated that metals with lower work function exhibit a better heat excitation capability, and polymers with lower fluorine content in molecule chains further boost the charge output, where metal/Kapton pairs demonstrated a charge promotion of over 2 times at the temperature of 383 K with good durability during 90 min measurement. The heat-excitation effect and charge durability in sliding freestanding-triboelectric-layer (SFT) mode triboelectric nanogenerator (TENG) is demonstrated as well, where the energy is promoted by over 3 times and the capacitor charging speed is doubled as well, with an energy promotion from 109.34 to 373 µJ per cycle to successfully trigger a discharger. This work suggests a promising future of the heat-excitation effect as a new charge promotion strategy for TENG toward different applications in high-temperature environments.

Exploring mismatch negativity in children with congenital Microtia-Atresia: A Preliminary study.

BACKGROUND: To investigate the characteristics of mismatch negativity (MMN) in terms of latency and amplitude in children with bilateral congenital microtia using a Bone conduction implant (Bonebridge), and to explore the relationship between cortical level auditory discrimination, speech perception, and psychosocial well-being. METHODS: This descriptive, observational, cross-sectional study compared three groups: eight children with bilateral congenital microtia and Bonebridge implants (bilateral group), eight children with unilateral congenital microtia and no hearing aids (unilateral group), and eight children with normal hearing (NH group). Participants underwent MMN evaluation using a classic oddball paradigm with a pure tone burst stimulus, featuring a 1000 Hz standard stimulus and a 1200 Hz deviant stimulus, presented in a sound field at 65 dBHL. Additionally, speech perception tests, the Meaningful Use of Speech Scale (MUSS), and psychosocial status questionnaires, including the Social Anxiety Scale for Children (SASC) and the Children's Loneliness Scale (CLS), were administered to all subjects. RESULTS: The bilateral group's average MMN latency was 241.23 ± 29.47 ms, and the unilateral group's was 209.96 ± 54.32 ms, both significantly longer than the NH group's 146.05 ± 15.73 ms (p < 0.0001, F=3.509, 95 % CI 68.09 to 122.3 and p = 0.0097, F=11.92, 95 % CI 18.07 to 109.8, respectively). However, no significant difference was found in MMN latency between the bilateral and unilateral groups (p = 0.202, F=3.397, 95 % CI -18.84 to 81.36). The unilateral group scored significantly higher on the MUSS (38.63 ± 1.41 vs. 30.75 ± 3.80, p = 0.0001, F=7.276, 95 % CI -11.16 to -4.590), had lower CLS scores (47.13 ± 8.13 vs. 58.25 ± 8.39, p = 0.024, F=1.065, 95 % CI 1.652 to 20.60), and lower SASC scores (4.13 ± 2.09 vs. 6.50 ± 2.25, p = 0.062, F=1.204, 95 % CI -0.138 to 4.89) compared to the bilateral group. MMN latency in the bilateral group correlated with SASC scores. CONCLUSION: The MMN latency in congenital microtia patients may serve as an indicator of central auditory discrimination capabilities. In children with bilateral congenital microtia and Bonebridge implants, MMN latency can reflect social anxiety conditions to a certain degree.

Avoidable Hospitalizations in Frail Older Adults: The Role of Sociodemographic, Clinical, and Care-Related Factors.

OBJECTIVES: This study aims to investigate the relationship between frailty and avoidable hospitalization risk, and the moderating role of sociodemographic, clinical, and care-related factors. DESIGN: Longitudinal population-based cohort study. SETTING AND PARTICIPANTS: A total of 3168 community-dwelling individuals, aged ≥60 years, from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). METHODS: We operationalized physical frailty using baseline SNAC-K data (2001-2004). In line with the Swedish Board of Health and Welfare and Association of Local Authorities and Regions, avoidable hospitalizations were considered those that could have been prevented through proper and timely outpatient care and identified through the Swedish National Patient Register. Participants were followed from baseline until first avoidable hospitalization, death, drop out, institutionalization, or maximum 12 (median 7.6) years. The association between frailty and avoidable hospitalization was explored through flexible parametric survival models, with stratified analyses to investigate age, gender, education, civil status, multimorbidity, cognitive status, and informal and formal care as potential modifiers. RESULTS: The adjusted 12-year cumulative incidence of avoidable hospitalization was significantly higher for frail persons (cumulative incidence 33.2%, 95% CI 28.9%-38.1%) than for prefrail (cumulative incidence 26.6%, 95% CI 24.5%-29.0%) and nonfrail (cumulative incidence 25.2%, 95% CI 22.5%-28.3%) individuals. In addition, prefrailty [hazard ratio (HR) 1.21, 95% CI 1.00-1.45] and frailty (HR 1.91, 95% CI 1.47-2.50) were associated with increased avoidable hospitalization hazards. Furthermore, the association between frailty and avoidable hospitalization was stronger in older adults aged <78 years (HR 3.12, 95% CI 1.99-4.91) and those with relatively fewer chronic diseases (HR 3.88, 95% CI 1.95-7.72), whereas provision of formal social care (HR 1.15, 95% CI 0.77-1.72) seemed to act as a buffer. CONCLUSIONS AND IMPLICATIONS: Our results indicate that older community-dwelling adults with prefrailty and frailty are at increased risk of experiencing avoidable hospitalizations, highlighting a need for better care of these individuals at the outpatient level. Formal social care services and close monitoring of particularly vulnerable subgroups of frail persons may mitigate this risk.

Association of Systemic Inflammatory Response Index and Neutrophil-to-Lymphocyte Ratio on Unfavorable Functional Outcomes in Acute Ischemic Stroke Patients After Endovascular Therapy.

BACKGROUND: Inflammatory markers for the prognosis of acute ischemic stroke (AIS) with endovascular therapy remain unclear. The purpose of this study was to investigate the association between the systemic inflammatory response index (SIRI) and neutrophil-to-lymphocyte ratio (NLR) with unfavorable functional outcomes at 90-day in individuals of AIS who underwent endovascular therapy. METHODS: A total of 128 AIS patients who had endovascular therapy were enrolled from the Nanjing Stroke Registry between September 2019 and November 2022. Peripheral venous blood was collected from patients within 24 h of admission for information on the following parameters: neutrophil count, lymphocyte count, and monocyte count. Then, the SIRI and NLR values were calculated and the association among SIRI, NLR, and modifled Rankin Scale scores 90 days after endovascular therapy was examined via univariate and multivariate logistic analyses. Receiver operating characteristic curves were utilized to determine the best threshold for SIRI and NLR in predicting negative neurological outcomes following endovascular treatment for patients with AIS. RESULTS: A total of 128 participants were evaluated, among which 50% had unfavorable outcomes. Linear regression analysis showed that the best threshold for SIRI was >1.407 (odds ratio = 1.265; 95% confidence interval, 1.071-1.493; P = 0.006), and for NLR it was >5.347 (odds ratio = 1.088; 95% confidence interval, 1.007-1.175; P = 0.033). These results revealed NLR and SIRI as significant predictors of unfavorable outcomes at 90 days. The area under the curve for SIRI and NLR in predicting 90-day adverse outcomes was 0.643 and 0.609, respectively. CONCLUSIONS: Higher SIRI and NLR levels at admission may lead to unfavorable outcomes at 90 days for AIS patients with endovascular therapy.

Personal Norms Predict Defending in Bullying: Mediating Role of Anticipated Pride and Guilt.

Recent studies have shown that bystander intervention involves moral engagement. However, the underlying internal mechanism is still poorly understood. Drawing on the norm activation model (NAM), Study 1 (questionnaire; n = 502) and Study 2 (experiment; n = 144) were conducted to investigate the influence of personal norms on defending through the mediating factors of anticipated pride and anticipated guilt. After controlling for age and gender, Study 1 revealed a significant positive association between personal norms and defending. This relationship was mediated by both anticipated pride and guilt, highlighting their parallel roles in explaining the influence of personal norms on defending. Study 2 investigated using writing tasks to manipulate personal norms from participants. The results revealed that the priming group had significantly higher levels of anticipated pride, guilt, and defending than the control group. Study 2 replicated the results of Study 1 in testing the mediated path, enhancing the reliability of research findings. This study expands the scope of the application of NAM by examining the interplay between personal norms, anticipated pride, anticipated guilt, and defending, as well as exploring the implications of these findings for interventions against bullying. Moral education should focus not only on the responsibility and obligation of bystanders to intervene in bullying incidents but also on the need to assist students in forming a moral compass within themselves that guides them to defend victims through moral emotions actively.

Acute and long COVID-19 symptoms and associated factors in the omicron-dominant period: a nationwide survey via the online platform Wenjuanxing in China.

BACKGROUNDS: To our knowledge, there is no available nationwide data on omicron symptom patterns in China mainland. We aim to determine the acute and long COVID-19 symptoms in the omicron-dominant period and to evaluate its association with risk factors. METHODS: We designed a cross-sectional nationwide study and data about self-reported symptoms were collected by an online platform named Wenjuanxing. Eligible participants were aged 25-65 years and were symptomatic. In this study, the ratios of the number of people of different ages and genders were weighted by the data from the Seventh National Census (2020 years), and validated by a published nationwide representative study through comparing smoking rates. Descriptive indicators were calculated for demographic characteristics, diagnosis ways, and duration time, acute symptoms, hospitalization, severity and long COVID-19 symptoms. And, the associations between risk factors and acute and long COVID-19 symptoms were analyzed by multivariable logistic regression models. RESULTS: A total of 32,528 individuals diagnosed as COVID-19 infection from October 1, 2022 to February 21, 2023 were included. The first three acute symptoms of COVID-19 infection were fever (69.90%), headache (62.63%), and sore throat (54.29%), respectively. The hospitalization rate within 7 days was 3.07% and symptoms disappearance rate within 21 days was 68.84%, respectively. Among 3983 COVID-19 patients with 3 months or more time difference between first infection and participation into the study, the long COVID-19 rate was 19.68% and the primary symptoms were muscle weakness (19.39%), headache (17.98%) and smell/taste disorder (15.18%). Age groups, smoking, marriage status and vaccination were risk factors for numbers of acute phase symptoms and long COVID-19 symptoms. Lastly, female and current smokers also showed more numbers of symptoms during acute infection period. CONCLUSIONS: In Chinese mainland, our respondent indicated that current smokers and women were associated with acute COVID-19 symptoms, which should be treated with caution due to the lack of representative.

Reversal of injury-associated retinal ganglion cell gene expression by a phosphodiesterase anchoring disruptor peptide.

Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased RGC cAMP signaling is neuroprotective. We have shown that displacement of the cAMP-specific phosphodiesterase PDE4D3 from an RGC perinuclear compartment by expression of the modified PDE4D3 N-terminal peptide 4D3(E) increases perinuclear cAMP and protein kinase A activity in cultured neurons and in vivo RGC survival after optic nerve crush (ONC) injury. To explore mechanisms by which PDE4D3 displacement promotes neuroprotection, in this study mice intravitreally injected with an adeno-associated virus to express an mCherry-tagged 4D3(E) peptide were subjected to ONC injury and analyzed by single cell RNA-sequencing (scRNA-seq). 4D3(E)-mCherry expression was associated with an attenuation of injury-induced changes in gene expression, thereby supporting the hypothesis that enhanced perinuclear PKA signaling promotes neuroprotective RGC gene expression.

The Roles of RNA N6-methyladenosine Modifications in Systemic Lupus Erythematosus.

N6-methyladenosine (m6A) modification is the most widespread RNA internal modification involved in RNA metabolism. M6A regulators consist of writers, erasers and readers. They exert their function by methylation, demethylation and recognization respectively, participating in cell biology and immune responses. Previously, the focus of m6A modification is its effect on tumor progress. Currently, extensive m6A-related studies have been performed in autoimmune diseases, such as RA, IBD and SLE, revealing that the unique influence of m6A modification in autoimmunity is undeniable. In this review, we summarize the function of m6A regulators, analyze their roles in pathogenic immune cells, summarize the m6A modification in SLE, and provide the potential m6A-targeting therapies for autoimmune diseases.

Effectiveness of acupuncture in treating patients with pain and mental health concerns: the results of the Alberta Complementary Health Integration Project.

Background: This study presents real-world evidence on the clinical outcomes of the Alberta Complementary Health Integration Project (ABCHIP), which utilized acupuncture to address pain and mental health issues in two vulnerable populations in Alberta: youth (aged 24 and below) and elderly (aged 55 and above). Methods: Over 282 days, a total of 606 patients received 5,424 acupuncture treatments. Tailored to each patients' specific pain and mental health concerns, an individualized treatment plan was selected, following a standard treatment protocol lasting 1 to 3 months. Patients were evaluated at least twice: initially and upon completing therapy. Primary treatment outcomes were assessed using various measures, including the Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire 9 (PHQ9), PROMIS Anxiety 8a and its pediatric form PROMIS Anxiety-Pediatric, PROMIS Short Form v1.0 Fatigue 8a and its pediatric counterpart PROMIS Pediatric Short Form v2.0 Fatigue 10a, PROMIS Short Form v1.1 Anger 5a and its version PROMIS SF v2.0 5a, and EQ-5D-5L. These measures gauged pain reduction, improved sleep quality, reduced depression, anxiety, fatigue, anger, and quality of life, respectively. Results: Analysis of data from 500 patients who received at least 6 acupuncture sessions through ABCHIP showed statistically significant improvements in clinical outcomes. Among this group, the subgroup of 235 patients who received at least 12 sessions demonstrated the most favorable treatment outcomes, including an 75.5% reduction in pain severity, a 53.1% improvement in sleep quality, a 78.4% drop in depression, a 41.1% decline in anxiety, a 43.7% decrease in fatigue, a 38.2% decrease in anger, and a 42.6% improvement in overall quality of life. Conclusion: Integrating acupuncture with usual care demonstrates promise in enhancing mental health, alleviating chronic and general pain, and improving overall quality of life. The findings suggest that integrative programs, such as ABCHIP, present an effective approach to addressing pain and mental health concerns in vulnerable populations, providing valuable insights for future healthcare interventions.

Exploration of ETV6::ABL1-positive AML with concurrent NPM1 and FLT3-ITD mutations.

ETV6::ABL1 is a rare fusion gene that found in MPN, ALL, and AML. It has a complex and diverse formation mechanism due to the reciprocal orientations of the ETV6 and ABL1 genes relative to the centromeres. NPM1 is frequently mutated in adult AML, often accompanied by FLT3-ITD, which suggests molecular synergisms in AML pathogenesis. Previous reports on ETV6::ABL1 mostly focus on FLT3-ITD. In this study, we present a case of AML with ETV6::ABL1, along with NPM1 and FLT3-ITD. The patient showed a rapid increase in primitive cells at the initial stage, along with the presence of immature granulocytes and erythrocytes. Through cytogenetic analysis, fluorescence in situ hybridization (FISH), and RNA-seq, we elucidated the mechanism behind the formation of the ETV6::ABL1 fusion gene. Despite conventional chemotherapy failure and rapid tumor proliferation, we attempted to add FLT3 inhibitor sorafenib to the treatment, along with chemotherapy bridging to haploidentical transplantation. After haplo-HSCT, a combination of sorafenib and dasatinib was administered as maintenance therapy. The patient achieved complete remission (CR) and maintained it for 11 months. The intricate genetic landscape observed in this case presents diagnostic dilemmas and therapeutic challenges, emphasizing the importance of a comprehensive understanding of its implications for disease classification, risk stratification, and treatment selection.

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

Efficient 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.

Perioperative and oncologic outcomes of robot-assisted versus open surgery for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to compare perioperative and oncologic outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) treated with robotic-assisted surgery versus open laparotomy. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) and cohort studies up to June 15, 2024, were identified using PubMed, EMBASE, and Google Scholar. Additionally, reference lists of included studies, relevant review articles, and clinical guidelines were manually searched. The primary outcomes evaluated were length of stay, 90-day mortality, postoperative pancreatic fistula (POPF), and Post-pancreatectomy haemorrhage (PPH). Secondary outcomes included estimated blood loss, reoperation rate, lymph node yield, and operative time. The final analysis included 10 retrospective cohort studies involving 23,272 patients (2,179 robotic-assisted and 21,093 open surgery). There were no significant differences between the two procedures in terms of postoperative pancreatic fistula, Post-pancreatectomy haemorrhage, lymph node yield, and operative time. However, patients undergoing robotic-assisted surgery had shorter lengths of stay, lower 90-day mortality, and less estimated blood loss compared to those undergoing open surgery. The reoperation rate was higher for the robotic-assisted group. Robotic-assisted surgery for pancreatic ductal adenocarcinoma is safe and feasible. Compared to open surgery, it offers better perioperative and short-term oncologic outcomes, but with a higher risk of reoperation.

Associations of parity and cognitive decline, depression, and chronic comorbidity in West China: Results from WCHAT study.

OBJECTIVE: To investigate the associations between parity (the number of offspring a female has borne) and cognitive function, depression, and chronic comorbidity in Western China. METHODS: A total of 846 women aged 50-55 years were included in the current analysis. Cognitive status was measured using a 10-item short portable mental status questionnaire (SPMSQ). Depressive symptoms were assessed using the 15-item geriatric depression scale (GDS-15). Other characteristics were self-reported. The associations between parity and cognitive decline, depression, and chronic comorbidity were analyzed using univariable and multivariable models. Multivariable models were adjusted for age, ethnic group, occupation, marital status, educational level, lifestyle factors, and sleeping time. RESULTS: Among the enrolled women, 26.71% were either childless or had one child, 47.40% had two children, 18.32% had three children, and 7.57% had ≥4 children. Compared to women with low parity, women with two or more children exhibited a higher risk of cognitive decline. Moreover, having four or more children was significantly associated with depression and chronic comorbidity. After adjusting covariates, women with three or more children exhibited a higher risk of cognitive decline than those with low parity. However, high parity was not significantly associated with depression or chronic comorbidity after adjustment for covariates. CONCLUSION: Our study showed that ≥3 children was associated with cognitive decline in women. Longitudinal studies are needed to evaluate this conclusion and to investigate the mechanisms involved. More importantly, families and societies should pay more attention to women's long-term health outcomes related to fertility.

Biomimetic bimodal haptic perception using triboelectric effect.

Multimodal haptic perception is essential for enhancing perceptual experiences in augmented reality applications. To date, several artificial tactile interfaces have been developed to perceive pressure and precontact signals, while simultaneously detecting object type and softness with quantified modulus still remains challenging. Here, inspired by the campaniform sensilla on insect antennae, we proposed a hemispherical bimodal intelligent tactile sensor (BITS) array using the triboelectric effect. The system is capable of softness identification, modulus quantification, and material type recognition. In principle, due to the varied deformability of materials, the BITS generates unique triboelectric output fingerprints when in contact with the tested object. Furthermore, owing to the different electron affinities, the BITS array can accurately recognize material type (99.4% accuracy), facilitating softness recognition (100% accuracy) and modulus quantification. It is promising that the BITS based on the triboelectric effect has the potential to be miniaturized to provide real-time accurate haptic information as an artificial antenna toward applications of human-machine integration.

Neoadjuvant chemoimmunotherapy for small cell carcinoma of the esophagus: Clinical efficacy and biomarker exploration.

Small cell carcinoma of the esophagus (SCCE) is a rare and highly malignant type of esophageal cancer with no standard treatment, facing challenges of resistance to conventional therapies. This study presents the cases of one extensive-stage and two limited-stage SCCE patients treated with chemoimmunotherapy. The two limited-stage patients underwent surgery post-treatment and experienced notable and enduring positive responses. This represents the first documented application of neoadjuvant chemoimmunotherapy in limited-stage SCCE patients. Additionally, comprehensive immunohistochemical analysis and whole exome sequencing were performed on the case patients. The findings revealed that infiltration of CD8+ T cells and PD-L1 expression in the SCCE tumor were key factors for favorable responses in SCCE patients receiving chemoimmunotherapy.

Photoinduced copper catalyzed nitrogen-to-alkyl radical relay Sonogashira-type coupling of o-alkylbenzamides with alkynes.

This report describes a copper-catalyzed, photoinduced N-to-alkyl radical relay Sonogashira-type reactions at benzylic sites in o-alkylbenzamides with alkynes. The process employs an N-to-alkyl radical mechanism, initiated through the copper-catalyzed reductive generation of nitrogen radicals. Radical translocation is facilitated by a 1,5-hydrogen atom transfer (1,5-HAT), leading to the formation of translocated carbon radicals. These radicals are then subjected to copper-catalyzed alkynylation. The methodology exhibits broad sub-strate scope and applicability to the synthesis of complex natural products.