Iron-catalyzed benzylic C-H thiolation via photoinduced ligand-to-metal charge-transfer.

Here, we describe an iron-catalyzed benzylic C-H thiolation of alkylarenes via photoinduced ligand-to-metal charge-transfer. The protocol features operational simplicity, mild reaction conditions, and the use of FeCl3 as catalyst and thiols/disulfides as sulfur sources, which enables the transformation of diverse benzylic C-H bonds into C-S bonds with a high efficiency.

Exosome Isolation and Detection: From Microfluidic Chips to Nanoplasmonic Biosensor.

Exosomes are becoming more widely acknowledged as significant circulating indicators for the prognosis and diagnosis of cancer. Circulating exosomes are essential to the development and spread of cancer, according to a growing body of research. Using existing technology, characterizing exosomes is quite difficult. Therefore, a direct, sensitive, and targeted approach to exosome detection will aid in illness diagnosis and prognosis. The review discusses the new strategies for exosome isolation and detection technologies from microfluidic chips to nanoplasmonic biosensors, analyzing the advantages and limitations of these new technologies. This review serves researchers to better understand exosome isolation and detection methods and to help develop better exosome isolating and detecting devices for clinical applications.

Emerging Insights into Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Induced by Immune Checkpoint Inhibitor and Tumor-Targeted Therapy.

Objective: Anticancer drugs have revolutionized tumor therapy, with cutaneous toxicities such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) being common immune-related adverse events. The debate over the efficacy of systemic corticosteroids in treating these conditions persists, while tumor necrosis factor (TNF)-alpha inhibitors show promise. This study aims to evaluate the effectiveness and safety of combination therapy involving the TNF-α inhibitor adalimumab for SJS/TEN induced by anticancer drugs. Methods: A literature review of SJS/TEN cases induced by anticancer drugs from 1992 to 2023 was conducted, alongside an analysis of patients admitted to the First Affiliated Hospital of Fujian Medical University during the same period. Clinical characteristics, skin healing time, mortality, and adverse events were evaluated in two treatment groups: SJS/TEN patients treated with targeted anticancer therapies and immunotherapies. Results: Among the 27 patients studied (18 with SJS or SJS-TEN overlapping and 9 with TEN), combination therapy with adalimumab significantly reduced mucocutaneous reepithelization time and healing duration compared to corticosteroid monotherapy. Patients receiving adalimumab combined with corticosteroids had lower actual mortality rates than those on corticosteroid monotherapy. The combination therapy also showed a trend towards reducing standardized mortality rates based on the Score of Toxic Epidermal Necrolysis (SCORTEN). Conclusion: The findings suggest that adalimumab in combination with corticosteroids provides significant clinical benefits and is safer than corticosteroids alone for treating SJS/TEN induced by targeted anticancer therapies and immunotherapies. This study contributes valuable insights into potential treatment strategies for severe cutaneous adverse reactions to anticancer drugs, highlighting the importance of exploring alternative therapies such as TNF-α inhibitors in managing these conditions effectively.

Dual sensitivity-enhanced microring resonance-based integrated microfluidic biosensor for Aß42 detection.

Sensitive, accurate, and straightforward biosensors are pivotal in the battle against Alzheimer's disease, particularly in light of the escalating patient population. These biosensors enable early adjunctive diagnosis, thereby facilitating prompt intervention, alleviating socioeconomic burdens, and preserving individual well-being. In this study, we introduce the development of a highly sensitive add-drop dual-microring resonant microfluidic sensing chip boasting a sensitivity of 188.11 nm/RIU, marking a significant 20.7% enhancement over single microring systems. Leveraging ultra-thin Parylene C for streamlined antibody immobilization and non-destructive removal, this platform facilitates the precise quantification of the Alzheimer's disease biomarker Aß42. Employing an immune sensing strategy that amplifies and captures antigen signals using Au-labeled antibodies, we achieve an exceptional limit of detection of 9.02 pg/mL. The designed microring-based microfluidic biosensor chip exhibits outstanding specificity and sensitivity for Aß42 in serum samples, offering a promising avenue for the early adjunctive diagnosis of Alzheimer's disease.

Ultrasensitive Silicon Photonic Refractive Index Sensor Based on Hybrid Double Slot Subwavelength Grating Microring Resonator.

Silicon photonic-based refractive index sensors are of great value in the detection of gases, biological and chemical substances. Among them, microring resonators are the most promising due to their compact size and narrow Lorentzian-shaped spectrum. The electric field in a subwavelength grating waveguide (SWG) is essentially confined in the low-refractive index dielectric, favoring enhanced analyte-photon interactions, which represents higher sensitivity. However, it is very challenging to further significantly improve the sensitivity of SWG ring resonator refractive index sensors. Here, a hybrid waveguide blocks double slot subwavelength grating microring resonator (HDSSWG-MRR) refractive index sensor operating in a water refractive index environment is proposed. By designing a new waveguide structure, a sensitivity of up to 1005 nm/RIU has been achieved, which is 182 nm/RIU higher than the currently highest sensitivity silicon photonic micro ring refractive index sensor. Meanwhile, utilizing a unique waveguide structure, a Q of 22,429 was achieved and a low limit of detection of 6.86 × 10-5 RIU was calculated.

Ultrathin Parylene C-based sensitivity-gain nanoplasmonic sensor integrated on VCSEL for Aß42 detection.

As Alzheimer's disease prevalence continues to rise, there is an increasing demand for efficient on-chip biosensors capable of early biomarker detection. This study presents a novel biosensor chip leveraging vertical cavity surface emitting laser (VCSEL) technology, with Parylene C serving as the antibody coupling layer and utilizing a streamlined one-step antibody modification method. Integration of Parylene C enhances chip sensitivity from 34.28 µW/RIU to 40.32 µW/RIU. Moreover, post-testing removal of Parylene C enables chip reusability without significant alteration of results. The sensor demonstrates effective detection of Aß42, an Alzheimer's biomarker, exhibiting a linear range of 1-200 ng/mL and a detection limit of 0.26 ng/mL. These findings underscore the reusability and reliability of the ultrathin Parylene C-based VCSEL biosensor chip, highlighting its potential for point-of-care Alzheimer's disease diagnosis.

Stability Analysis of Metal Active-Gas Welding Short-Circuiting Transfer Based on Input Pulsating Energy.

In this study, a platform for a welding experiment, used to collect input and output electrical signals, was constructed, and the algorithm for the input pulsating energy interpolation line (IPEI) was given. Experiments with MAG surface straight line welding were conducted at various voltages. Analysis of the IPEI in relation to the welding current was performed while combining real-world welding occurrences with high-speed camera images of droplet transfer. It was established that the IPEI can be employed as a characteristic parameter to assess the stability of the short-circuiting transfer process in MAG welding. The three criteria for assessing the stability were the spectrum, approximation entropy, and coefficient of variation. A comparative analysis was conducted on each of these approaches. It was determined that the most effective technique is approximation entropy. The approximation entropy of the welding current and IPEI are also highly consistent, with a correlation coefficient as high as 0.9889.

Facile Construction of CuFe-Based Metal Phosphides for Synergistic NOx -Reduction to NH3 and Zn-Nitrite Batteries in Electrochemical Cell.

The electrocatalytic nitrite/nitrate reduction reaction (eNO2RR/eNO3RR) offer a promising route for green ammonia production. The development of low cost, highly selective and long-lasting electrocatalysts for eNO2RR/eNO3RR is challenging. Herein, a method is presented for constructing Cu3P-Fe2P heterostructures on iron foam (CuFe-P/IF) that facilitates the effective conversion of NO2 - and NO3 - to NH3. At -0.1 and -0.2 V versus RHE (reversible hydrogen electrode), CuFe-P/IF achieves a Faradaic efficiency (FE) for NH3 production of 98.36% for eNO2RR and 72% for eNO3RR, while also demonstrating considerable stability across numerous cycles. The superior performance of CuFe-P/IF catalyst is due tothe rich Cu3P-Fe2P heterstuctures. Density functional theory calculations have shed light on the distinct roles that Cu3P and Fe2P play at different stages of the eNO2RR/eNO3RR processes. Fe2P is notably active in the early stages, engaging in the capture of NO2 -/NO3 -, O─H formation, and N─OH scission. Conversely, Cu3P becomes more dominant in the subsequent steps, which involve the formation of N─H bonds, elimination of OH* species, and desorption of the final products. Finally, a primary Zn-NO2 - battery is assembled using CuFe-P/IF as the cathode catalyst, which exhibits a power density of 4.34 mW cm-2 and an impressive NH3 FE of 96.59%.

Freezing and thawing of cells on a microfluidic device: a simple and time-saving experimental procedure.

Developing cell cryopreservation methods on chips is not only crucial for biomedical science but also represents an innovative approach for preserving traditional cell samples. This study presents a simple method for direct cell freezing and thawing on chip, allowing for long-term storage of cells. During the freezing process, cells were injected into the microchannel along with a conventional cell cryopreservation solution, and the chip was packed using a self-sealing bag containing isopropyl alcohol and then stored in a -80°C refrigerator until needed. During the thawing process, microcolumn arrays with a spacing of 8 µm were strategically incorporated into the microfluidic chip design to effectively inhibit cells from the channel. The breast cancer cell lines MDA-MB-231 and B47D demonstrated successful thawing and growth after cryopreservation for 1 month to 1 year. These findings offer a direct cell freezing and thawing method on a microfluidic chip for subsequent experiments.

Electrochemical Radical Reaction Construction of C-C Bonds: Access to 1,4-Dicarbonyl Compounds from Enol Acetates and 1,3-Diketones.

As important substrates for the construction of heterocycles, a simple and efficient approach for synthesis of 1,4-diones is highly desirable. In this work, novel and efficient electrochemical radical reactions of enol acetates and 1,3-diketones have been developed to successfully achieve 1,4-diketones under catalyst-free and oxidant-free conditions. The wide range of substrates, good group tolerance, and simple operation process make the approach have important practical value. Moreover, the obtained 1,4-diketones can be easily further transformed to pyrrole and furan derivatives.

Discovery of (S)-N1-(thiazol-2-yl) pyrrolidine-1,2-dicarboxamide derivatives targeting PI3Ka/HDAC6 for the treatment of cancer.

Recently, PI3K and HDAC have been considered as promising targets for the cancer therapy. A couple of pan-PI3K/HDAC dual inhibitors have been developed as a new class of anticancer agents. Herein, we discovered a new series of (S)-N1-(thiazol-2-yl) pyrrolidine-1,2-dicarboxamide derivatives targeting PI3Kα/HDAC6. All the derivatives exerted dual-target inhibitory activities. Particularly, in the enzymatic selectivity assay, compound 21j was identified as a subtype-selective PI3Kα/HDAC6 dual inhibitor (IC50 = 2.9 and 26 nM against PI3Kα and HDAC6, respectively), which displayed high potency against L-363 cell line with IC50 value of 0.17 µM. In addition, 21j significantly inhibited phosphorylation of pAkt(Ser473) and induced accumulation of acetylated α-tubulin while having a negligible effect on the levels of acetylated Histone H3 and H4 at nanomolar level. Attributed to its favorable in vitro performance, 21j has the potential to alleviate the adverse effects resulted from pan-PI3K inhibition and pan-HDAC inhibition. It is valuable for further functional investigation as an anti-cancer agent.

Meerwein Arylation of Aryl(alkyl)idenemalononitriles and Diazonium Salts for the Synthesis of 2-(Aryl(alkyl)/arylmethylene)malononitrile Derivatives.

A metal-free Meerwein arylation reaction from aryl(alkyl)idenemalononitriles and diazonium salts for the synthesis of 2-(aryl(alkyl)/arylmethylene)malononitrile derivatives under mild conditions was well developed. Different from the general addition reactions between alkenes and diazonium salts, this study performed the traditional coupling reaction for the formation of C(sp2)-C(sp2) bond arylation products. The radical reaction mechanism was well verified in the control experiments. The other advantages of the approach are broad-scope substrates and good group tolerance. Moreover, the obtained products can be readily converted into high-value asymmetric ketones and hydrogenation reactions.

Aberrant mRNA processing caused by splicing mutations in TTN-related neuromuscular disorders.

Mutations in the TTN gene have been reported to be responsible for a range of neuromuscular disorders, including recessive distal myopathy and congenital myopathy (CM). Only five splicing mutations have been identified to induce aberrant mRNA splicing in TTN-related neuromuscular disorders. In our study, we described detailed clinical characteristics, muscle pathology and genetic analysis of two probands with TTN-related autosomal recessive neuromuscular disorders. Besides, we identified two novel intronic mutations, c.107377+1 G > C in intron 362 and c.19994-2 A > G in intron 68, in the two probands. Through cDNA analysis, we revealed the c.107377+1 G > C mutation induced retention of the entire intron 362, and the c.19994-2 A > G mutation triggered skipping of the first 11 bp of exon 69. Our study broadens the aberrant splicing spectrum of neuromuscular disorders caused by splicing mutations in the TTN gene.

Exploitation of Proximity-Mediated Effects in Drug Discovery: An Update of Recent Research Highlights in Perturbing Pathogenic Proteins and Correlated Issues.

The utilization of proximity-mediated effects to perturb pathogenic proteins of interest (POIs) has emerged as a powerful strategic alternative to conventional drug design approaches based on target occupancy. Over the past three years, the burgeoning field of targeted protein degradation (TPD) has witnessed the expansion of degradable POIs to membrane-associated, extracellular, proteasome-resistant, and even microbial proteins. Beyond TPD, researchers have achieved the proximity-mediated targeted protein stabilization, the recruitment of intracellular immunophilins to disturb undruggable targets, and the nonphysiological post-translational modifications of POIs. All of these strides provide new avenues for innovative drug discovery aimed at battling human malignancies and other major diseases. This perspective presents recent research highlights and discusses correlated issues in developing therapeutic modalities that exploit proximity-mediated effects to modulate pathogenic proteins, thereby guiding future academic and industrial efforts in this field.

Label-free integrated microfluidic plasmonic biosensor from vertical-cavity surface-emitting lasers for SARS-CoV-2 receptor binding domain protein detection.

The nanoplasmonic sensor of the nanograting array has a remarkable ability in label-free and rapid biological detection. The integration of the nanograting array with the standard vertical-cavity surface-emitting lasers (VCSEL) platform can achieve a compact and powerful solution to provide on-chip light sources for biosensing applications. Here, a high sensitivity and label-free integrated VCSELs sensor was developed as a suitable analysis technique for COVID-19 specific receptor binding domain (RBD) protein. The gold nanograting array is integrated on VCSELs to realize the integrated microfluidic plasmonic biosensor of on-chip biosensing. The 850 nm VCSELs are used as a light source to excite the localized surface plasmon resonance (LSPR) effect of the gold nanograting array to detect the concentration of attachments. The refractive index sensitivity of the sensor is 2.99 × 106 nW/RIU. The aptamer of RBD was modified on the surface of the gold nanograting to detect the RBD protein successfully. The biosensor has high sensitivity and a wide detection range of 0.50 ng/mL - 50 µg/mL. This VCSELs biosensor provides an integrated, portable, and miniaturized idea for biomarker detection.

The clinical features and TCAP mutation spectrum in a Chinese cohort of patients with limb-girdle muscular dystrophy R7.

Limb-girdle muscular dystrophy R7 (LGMDR7) is an autosomal recessive hereditary muscular dystrophy caused by mutations in titin-cap (TCAP). Here, we summarized the clinical characteristics and TCAP mutations in a Chinese cohort of 30 patients with LGMDR7. The onset age of Chinese patients was 19.89 ± 6.70 years old, which is later than European and South Asian patients (P < 0.05). Clinically speaking, 20.0% of patients presented with predominant distal weakness, and 73.3% of patients presented with predominant pelvic girdle weakness. Radiological study revealed semitendinosus and magnus adductor were severely involved in Chinese LGMDR7 patients. Rectus femoris, vastus lateralis, vastus intermedius, soleus and tibialis anterior were moderately to severely involved. The most prevalent mutation in this cohort is c.26_33dupAGGTGTCG, while c.165dupG and c.110 + 5G > A are unique in Chinese population as two of the common mutations. Besides, variant c.26_33dupAGGGTGTCG might be a founder mutation in Asian patients. Internal nuclei, lobulated fibers, and scattered rimmed vacuoles were typical morphological changes in Chinese LGMDR7 patients. This is the largest LGMDR7 cohort in the Chinese population and in the world. This article also expands the clinical, pathological, mutational and radiological spectrum of patients with LGMDR7 in China and in the world.

Sensitivity-enhanced nanoplasmonic biosensor using direct immobilization of two engineered nanobodies for SARS-CoV-2 spike receptor-binding domain detection.

Sensitive, rapid, and easy-to-implement biosensors are critical in responding to highly contagious and fast-spreading severe acute respiratory syndrome coronavirus (SARS-CoV-2) mutations, enabling early infection screening for appropriate isolation and treatment measures to prevent the spread of the virus. Based on the sensing principle of localized surface plasmon resonance (LSPR) and nanobody immunological techniques, an enhanced sensitivity nanoplasmonic biosensor was developed to quantify the SARS-CoV-2 spike receptor-binding domain (RBD) in serum within 30 min. The lowest concentration in the linear range can be detected down to 0.01 ng/mL by direct immobilization of two engineered nanobodies. Both the sensor fabrication process and immune strategy are facile and inexpensive, with the potential for large-scale application. The designed nanoplasmonic biosensor achieved excellent specificity and sensitivity for SARS-CoV-2 spike RBD, providing a potential option for accurate early screening of the novel coronavirus disease 2019 (COVID-19).

Resilience of infertile families undergoing in vitro fertilization: An application of the double ABC-X model.

BACKGROUND: Family resilience plays a crucial role in protecting the mental health and family stability of infertile patients. However, information associated with infertile families resilience is scarce. The double ABC-X model provides a roadmap for this, helps organize knowledge, and lays the foundation for knowledge development. AIMS: To describe the current situation of family resilience of infertile women, and to test the predictive theoretical model of family resilience based on infertility stigma, individual resilience, coping style, and posttraumatic growth. DESIGN: A cross-sectional study. METHODS: A convenience sample of 372 infertile women undergoing in vitro fertilization were recruited between April and August 2020. The Chinese-Family Resilience Assessment Scale, Infertility Stigma Scale, Simplified Coping Style Questionnaire, Chinese version of Connor-Davidson Resilience Scale, and Chinese version of Post Traumatic Growth Inventory were used to measure family resilience, infertility stigma, individual resilience, coping style, and posttraumatic growth. Structural equation models were used to analyze the relationship among these variables. RESULTS: The results showed that family resilience was related to infertility stigma, positive coping, and individual resilience. Moreover, the path analysis indicated that positive coping and individual resilience mediated the effects of infertility stigma on family resilience. CONCLUSIONS: A high level of stigma among infertile women should be identified. Interventions for targeting positive coping and individual resilience might ultimately increase their family resilience.

Somatic and germinal mosaicism in a Han Chinese family with laminopathies.

"Laminopathies" refers to a wide spectrum of myopathies caused by mutations in the LMNA gene. These myopathies include limb girdle muscular dystrophy type 1B (LGMD1B) and dilated cardiomyopathy 1 A (DCM1A), which are both autosomal dominant neurogenetic diseases. There have been few studies on mosaicism in laminopathies. Herein, a Han Chinese family with laminopathies was enrolled in our study. Genetic analysis revealed that the proband carried a novel splice site mutation, c. 1158-3 C > T, in the LMNA gene due to her mother having de novo somatic and gonadal mosaicism. Reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed reduced levels of LMNA mRNA in the proband, which were probably due to nonsense-mediated mRNA decay (NMD). Western blotting revealed reduced lamin A/C protein levels in the skeletal muscle tissue of the proband. In this family, the clinical phenotypes of the proband's mother were normal, and the c. 1158-3 C > T splicing mutation was identified in the blood sample of the proband's mother. Thus, the mutation could be easily considered to be nonpathogenic. Our study emphasizes the importance of mosaicism in the identification of pathogenic variants and genetic counseling.

Direct α-C-H Alkylation of Structurally Diverse Alcohols via Combined Tavaborole and Photoredox Catalysis.

Herein, we report a method that uses antifungal tavaborole as a co-catalyst for direct α-C-H alkylation of structurally diverse alcohols through photoredox catalysis. The protocol features mild conditions, remarkable scope, and wide functional group tolerance, which allows for the construction of a wide array of highly functionalized alcohols, including homoserine derivatives and C-glycosyl amino acids. We also demonstrate the synthetic applications of this methodology to the late-stage functionalization of pharmaceuticals and natural products.