Repair of a "long and narrow" skin defect of the upper extremity with a modified design of a compound SCIP flap: a series of 12 cases.

BACKGROUND: Large skin lesions of the upper extremity tend to be ''long and narrow'' in shape, and the currently used repair and reconstruction protocols still have some drawbacks, including difficulty in closure of the donor area, poor cosmetic appearance of the donor and recipient areas, and low flap survival rates. The ilioinguinal flap has been more widely used for repair and reconstruction of various complex conditions. In order to improve the versatility of the flap design and to achieve better aesthetic results, we report a study on the improved design of Compound SCIP flap for repairing "long and narrow" large skin defects of the upper extremity by using a modified design of the ilioinguinal flap for the procurement of perforating blood vessels and flap excision. METHODS: From April 2005 to August 2015, a total of 12 patients underwent this modified design procedure, in which the anterior branch of the fourth lumbar artery or the posterior intercostal artery was selected to provide blood supply for the perforator flap together with the superficial branch of the superficial iliac artery to meet the blood supply needs of the flap for the one-time repair of a large "long and narrow" skin defect in the upper limb. Patient demographics, flap characteristics, and associated complications were retrospectively analyzed. RESULTS: 3 females and 9 males were included in this study, the mean age of the patients was 31.7 years (range, 22-44 years), the mean follow-up period was 15.3 ± 5.6 months (range, 7-24 months), and all patients had complete closure of the defect site and donor area, and all flaps survived. CONCLUSIONS: The Compound SCIP flap presents some advantages in repairing 'long and narrow' skin defects in the upper limb. While ensuring the survival rate of the elongated ilioinguinal flap, it amplifies the benefits of the ilioinguinal flap and enhances skin utilization. This can serve as a beneficial choice for repairing 'long and narrow' skin defects in the upper limb.

A Tiny Pocket Packs a Punch: Leveraging Pyridones for the Discovery of CNS-Penetrant Aza-indazole IRAK4 Inhibitors.

We herein report the discovery, synthesis, and evolution of a series of indazoles and azaindazoles as CNS-penetrant IRAK4 inhibitors. Described is the use of structure-based and property-based drug design strategically leveraged to guide the property profile of a key series into a favorable property space while maintaining potency and selectivity. Our rationale that led toward functionalities with potency improvements, CNS-penetration, solubility, and favorable drug-like properties is portrayed. In vivo evaluation of an advanced analogue showed significant, dose-dependent modulation of inflammatory cytokines in a mouse model. In pursuit of incorporating a highly engineered bridged ether that was crucial to metabolic stability in this series, significant synthetic challenges were overcome to enable the preparation of the analogues.

Analyzing relationships between latent topics in autonomous vehicle crash narratives and crash severity using natural language processing techniques and explainable XGBoost.

Safety is one of the most essential considerations when evaluating the performance of autonomous vehicles (AVs). Real-world AV data, including trajectory, detection, and crash data, are becoming increasingly popular as they provide possibilities for a realistic evaluation of AVs' performance. While substantial research was conducted to estimate general crash patterns utilizing structured AV crash data, a comprehensive exploration of AV crash narratives remains limited. These narratives contain latent information about AV crashes that can further the understanding of AV safety. Therefore, this study utilizes the Structural Topic Model (STM), a natural language processing technique, to extract latent topics from unstructured AV crash narratives while incorporating crash metadata (i.e., the severity and year of crashes). In total, 15 topics are identified and are further divided into behavior-related, party-related, location-related, and general topics. Using these topics, AV crashes can be systematically described and clustered. Results from the STM suggest that AVs' abilities to interact with vulnerable road users (VRUs) and react to lane-change behavior need to be further improved. Moreover, an XGBoost model is developed to investigate the relationships between the topics and crash severity. The model significantly outperforms existing studies in terms of accuracy, suggesting that the extracted topics are closely related to crash severity. Results from interpreting the model indicate that topics containing information about crash severity and VRUs have significant impacts on the model's output, which are suggested to be included in future AV crash reporting.

Applying the Wake-Up-like Effect to Enhance the Capabilities of Two-Dimensional Ferroelectric Field-Effect Transistors.

For traditional ferroelectric field-effect transistors (FeFETs), enhancing the polarization domain of bulk ferroelectric materials is essential to improve device performance. However, there has been limited investigation into the enhancement of polarization field in two-dimensional (2D) ferroelectric material such as CuInP2S6 (CIPS). In this study, similar to bulk ferroelectric materials, CIPS exhibited enhanced polarization field upon application of external cyclic voltage. Moreover, unlike traditional ferroelectric materials, the polarization enhancement of CIPS is not due to redistribution of the defect but rather originates from a mechanism: the long-distance migration of Cu ions. We termed this mechanism the "wake-up-like effect". After incorporating the wake-up-like effect into the graphene/CIPS/WSe2 FeFET device, we successfully increased the hysteresis window and enhanced the current on/off ratio by 4 orders of magnitude. Moreover, the FeFET yielded remarkable achievements, such as multilevel nonvolatile memory with 21 distinct conductance levels, a high on/off ratio exceeding 106, a long retention time exceeding 103 s, and neuromorphic computing with 93% accuracy at recognizing handwritten digits. Introducing the wake-up-like effect to 2D CIPS may pave the way for innovative approaches to achieve advanced multilevel nonvolatile memory and neuromorphic computing capabilities for next-generation micro-nanoelectronic devices.

Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection.

Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.

Elucidating salt-reduction mechanisms of aroma-active compounds from yeast extracts through sensomics approaches and electroencephalography.

This study investigated the savory intensity of aroma-active compounds derived from yeast extract Maillard reaction models. Sensory evaluation results revealed that beef flavoring model (28.00 g) exhibited the highest savory perception intensity when the yeast extract FA34 (0.50 g) the added. Eleven aroma-active compounds associated with saltiness perception were identified via solid-phase microextraction and extraction combined with gas chromatography-mass spectrometry/olfactory. The odorant-NaCl mixture model and saltiness intensity evaluation results revealed that thiazole and 4-methylpentanoic acid could significantly (p < 0.05) enhance the saltiness perception of salt solution (5.00 g/L), 2-methylpyrazine, 2-methyl-3-furanthiol, 2,6-dimethylpyrazine, furfuryl mercaptan, and methyl 2-methyl-3-furyl disulfide could significantly (p < 0.01) enhance the saltiness perception of a salt solution (5.00 g/L). Electroencephalography revealed that the main mechanisms underlying aroma-induced saltiness perception enhancement included the strengthening of the saltiness perception signal and prolonging signal stimulation time in the frontal regions of the cerebral cortex.

Gray matter volume and corresponding covariance connectivity are biomarkers for major depressive disorder.

The major depressive disorder (MDD) is a common and severe mental disorder. To identify a reliable biomarker for MDD is important for early diagnosis and prevention. Given easy access and high reproducibility, the structural magnetic resonance imaging (sMRI) is an ideal method to identify the biomarker for depression. In this study, sMRI data of first episode, treatment-naïve 66 MDD patients and 54 sex-, age-, and education-matched healthy controls (HC) were used to identify the differences in gray matter volume (GMV), group-level, individual-level covariance connections. Finally, the abnormal GMV and individual covariance connections were applied to classify MDD from HC. MDD patients showed higher GMV in middle occipital gyrus (MOG) and precuneus (PCun), and higher structural covariance connections between MOG and PCun. In addition, the Allen Human Brain Atlas (AHBA) was applied and revealed the genetic basis for the changes of gray matter volume. Importantly, we reported that GMV in MOG, PCun and structural covariance connectivity between MOG and PCun are able to discriminate MDD from HC. Our results revealed structural underpinnings for MDD, which may contribute towards early discriminating for depression.

RATA: A novel class A carbapenemase with broad geographic distribution and potential for global spread.

Carbapenem resistance's global proliferation poses a significant public health challenge. The primary resistance mechanism is carbapenemase production. In this study, we discovered a novel carbapenemase, RATA, located on the chromosome of Riemerella anatipestifer isolates. This enzyme shares ≤52 % amino acid sequence identity with other known ß-lactamases. Antimicrobial susceptibility tests and kinetic assays demonstrated that RATA could hydrolyze not only penicillins and extended-spectrum cephalosporins but also monobactams, cephamycins, and carbapenems. Furthermore, its activity was readily inhibited by ß-lactamase inhibitors. Bioinformatic analysis revealed 46 blaRATA-like genes encoding 27 variants in the NCBI database, involving 21 different species, including pathogens, host-associated bacteria, and environmental isolates. Notably, blaRATA-positive strains were globally distributed and primarily collected from marine environments. Concurrently, taxonomic analysis and GC content analysis indicated that blaRATA orthologue genes were predominantly located on the chromosomes of Flavobacteriaceae and shared a similar GC content as Flavobacteriaceae. Although no explicit mobile genetic elements were identified by genetic environment analysis, blaRATA-2 possessed the ability of horizontal transfer in R. anatipestifer via natural transformation. This work's data suggest that RATA is a new chromosome-encoded class A carbapenemase, and Flavobacteriaceae from marine environments could be the primary reservoir of the blaRATA gene.

Fully Integrated Multiplexed Wristwatch for Real-Time Monitoring of Electrolyte Ions in Sweat.

Considerable progress has already been made in sweat sensors based on electrochemical methods to realize real-time monitoring of biomarkers. However, realizing long-term monitoring of multiple targets at the atomic level remains extremely challenging, in terms of designing stable solid contact (SC) interfaces and fully integrating multiple modules for large-scale applications of sweat sensors. Herein, a fully integrated wristwatch was designed using mass-manufactured sensor arrays based on hierarchical multilayer-pore cross-linked N-doped porous carbon coated by reduced graphene oxide (NPCs@rGO-950) microspheres with high hydrophobicity as core SC, and highly selective monitoring simultaneously for K+, Na+, and Ca2+ ions in human sweat was achieved, exhibiting near-Nernst responses almost without forming an interfacial water layer. Combined with computed tomography, solid-solid interface potential diffusion simulation results reveal extremely low interface diffusion potential and high interface capacitance (598 µF), ensuring the excellent potential stability, reversibility, repeatability, and selectivity of sensor arrays. The developed highly integrated-multiplexed wristwatch with multiple modules, including SC, sensor array, microfluidic chip, signal transduction, signal processing, and data visualization, achieved reliable real-time monitoring for K+, Na+, and Ca2+ ion concentrations in sweat. Ingenious material design, scalable sensor fabrication, and electrical integration of multimodule wearables lay the foundation for developing reliable sweat-sensing systems for health monitoring.

Insights on updates in sodium alginate/MXenes composites as the designer matrix for various applications: A review.

Advancements in two-dimensional materials, particularly MXenes, have spurred the development of innovative composites through their integration with natural polymers such as sodium alginate (SA). Mxenes exhibit a broad specific surface area, excellent electrical conductivity, and an abundance of surface terminations, which can be combined with SA to maximize the synergistic effect of the materials. This article provides a comprehensive review of state-of-the-art techniques in the fabrication of SA/MXene composites, analyzing the resulting structural and functional enhancements with a specific focus on advancing the design of these composites for practical applications. A detailed exploration of SA/MXene composites is provided, highlighting their utility in various sectors, such as wearable electronics, wastewater treatment, biomedical applications, and electromagnetic interference (EMI) shielding. The review identifies the unique advantages conferred by incorporating MXene in these composites, examines the current challenges, and proposes future research directions to understand and optimize these promising materials thoroughly. The remarkable properties of MXenes are emphasized as crucial for advancing the performance of SA-based composites, indicating significant potential for developing high-performance composite materials.

In-situ precipitation zero-valent Co on Co2VO4 to activate oxygen vacancies and enhance bimetallic ions redox for efficient detection toward Hg(II).

Despite the widespread utilization of variable valence metals in electrochemistry, it is still a formidable challenge to enhance the valence conversion efficiency to achieve excellent catalytic activity without introducing heterophase elements. Herein, the in-situ precipitation of Co particles on Co2VO4 not only enhanced the concentration of oxygen vacancies (Ov) but also generated a greater number of low-valence metals, thereby enabling efficient reduction towards Hg(II). The electroanalysis results demonstrate that the sensitivity of Co/Co2VO4 towards Hg(II) was measured at an impressive value of 1987.74 µA µM-1 cm-2, significantly surpassing previously reported results. Further research reveals that Ov acted as the main adsorption site to capture Hg(II). The redox reactions of Co2+/Co3+ and V3+/V4+ played a synergistic role in the reduction of Hg(II), accompanied by the continuous supply of electrons from zero-valent Co to expedite the valence cycle. The Co/Co2VO4/GCE presented remarkable selectivity towards Hg(II), with excellent stability, reproducibility, and anti-interference capability. The electrode also exhibited minimal sensitivity fluctuations towards Hg(II) in real water samples, underscoring its practicality for environmental applications. This study elucidates the mechanism underlying the surface redox reaction of metal oxides facilitated by zero-valent metals, providing us with new strategies for further design of efficient and practical sensors.

Discovery of BIO-8169─A Highly Potent, Selective, and Brain-Penetrant IRAK4 Inhibitor for the Treatment of Neuroinflammation.

Interleukin receptor associated kinase 4 (IRAK4) plays an important role in innate immune signaling through Toll-like and interleukin-1 receptors and represents an attractive target for the treatment of inflammatory diseases and cancer. We previously reported the development of a potent, selective, and brain-penetrant imidazopyrimidine series of IRAK4 inhibitors. However, lead molecule BIO-7488 (1) suffered from low solubility which led to variable PK, compound accumulation, and poor in vivo tolerability. Herein, we describe the discovery of a series of pyridone analogs with improved solubility which are highly potent, selective and demonstrate desirable PK profiles including good oral bioavailability and excellent brain penetration. BIO-8169 (2) reduced the in vivo production of pro-inflammatory cytokines, was well tolerated in safety studies in rodents and dog at margins well above the predicted efficacious exposure and showed promising results in a mouse model for multiple sclerosis.

Transcriptomic atlas for hypoxia and following re-oxygenation in Ancherythroculter nigrocauda heart and brain tissues: insights into gene expression, alternative splicing, and signaling pathways.

Hypoxia is a mounting problem that affects the world's freshwaters, with severe consequence for many species, including death and large economical loss. The hypoxia problem has increased recently due to the combined effects of water eutrophication and global warming. In this study, we investigated the transcriptome atlas for the bony fish Ancherythroculter nigrocauda under hypoxia for 1.5, 3, and 4.5 h and its recovery to normal oxygen levels in heart and brain tissues. We sequenced 21 samples for brain and heart tissues (a total of 42 samples) plus three control samples and obtained an average of 32.40 million raw reads per sample, and 95.24% mapping rate of the filtered clean reads. This robust transcriptome dataset facilitated the discovery of 52,428 new transcripts and 6,609 novel genes. In the heart tissue, the KEGG enrichment analysis showed that genes linked to the Vascular smooth muscle contraction and MAPK and VEGF signaling pathways were notably altered under hypoxia. Re-oxygenation introduced changes in genes associated with abiotic stimulus response and stress regulation. In the heart tissue, weighted gene co-expression network analysis pinpointed a module enriched in insulin receptor pathways that was correlated with hypoxia. Conversely, in the brain tissue, the response to hypoxia was characterized by alterations in the PPAR signaling pathway, and re-oxygenation influenced the mTOR and FoxO signaling pathways. Alternative splicing analysis identified an average of 27,226 and 28,290 events in the heart and brain tissues, respectively, with differential events between control and hypoxia-stressed groups. This study offers a holistic view of transcriptomic adaptations in A. nigrocauda heart and brain tissues under oxygen stress and emphasizes the role of gene expression and alternative splicing in the response mechanisms.

Screening and identification of hub genes for ischemic cardiomyopathy and construction and validation of a clinical prognosis model using bioinformatics analysis.

Background: Myocardial ischemia and hypoxia may result in myocardial cell necrosis, scar formation, and hyperplasia. We aim to explore the differentially expressed genes (DEGs) in ischemic cardiomyopathy (ICM), construct and identify a clinical prognosis model using bioinformatics methods, so as to screen potential biomarkers of ICM to provide a basis for the early diagnosis and treatment of ICM. Methods: Based on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, R language was used to screen DEGs in healthy myocardial (n=5) and ICM myocardial tissues (n=12). DEGs were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI). Receiver operating characteristic (ROC) curves were drawn to verify the target genes. Results: A total of 259 genes with significantly changed fold change (FC) values were obtained through conditional screening, including up-regulated genes and down-regulated genes. The first two hub genes [interleukin-6 (IL-6) and Ras homologous gene family member A (RHOA)] with the largest degree value among the above up-regulated and down-regulated genes were selected and their expression values were combined in the gene chip to draw the ROC curve based on the pROC package of R language. The area under the ROC curve (AUC) values of IL-6 and RHOA were 0.956 and 0.995, respectively. The expression levels of Sqstm1, Nos2, IL-6, RHOA, and Zfp36 genes in the ICM group are lower than those in the blank control group and the difference was statistically significant (P<0.05). RHOA and Stat3 were identified as the key genes controlling the occurrence and development of ICM. Conclusions: ICM is closely related to the changes of extracellular matrix (ECM) and oxidoreductase activity. The IL-6 and RHOA are expected to become potential targets for ICM treatment.

Etiological diagnostic performance of probe capture-based targeted next-generation sequencing in bloodstream infection.

Background: A rapid and precise etiological diagnosis is crucial for the effective treatment of bloodstream infection (BSI). In this study, the performance of probe capture-based targeted next-generation sequencing (tNGS) was compared to that of blood culture and metagenomic next-generation sequencing (mNGS) in detecting potential pathogens in patients with BSI. Methods: A total of 80 patients with suspected BSI were prospectively enrolled from 24 November 2023 to 30 December 2023 at Zhongshan Hospital, Shanghai, China. All 80 participants underwent simultaneous blood culture, blood mNGS, and blood tNGS after admission when febrile, and the results were compared. Results: Among the 80 participants, 11 were clinically diagnosed with noninfectious fever, and 69 were diagnosed with BSI. Blood tNGS had a higher sensitivity for the diagnosis of BSI than blood culture (91.3% vs. 23.2%, P<0.001) and blood mNGS (91.3% vs. 69.6%, P=0.001). There was no significant difference in specificity between blood mNGS and tNGS (81.8% vs. 100.0%, P=0.13). Blood tNGS demonstrated a faster turnaround time than blood culture and blood mNGS. In 22 (31.9%) patients with BSI, targeted adjustment of the anti-infectious therapy according to the blood tNGS results resulted in clinical improvement. Conclusions: Blood tNGS may be a promising tool for detecting potential pathogens in patients with BSI. The application of blood tNGS for BSI could guide anti-infectious treatment strategies and might improve clinical outcomes.

Multiple-component covalent organic frameworks for simultaneous extraction and determination of multitarget pollutants in sea foods.

Persistent organic pollutants (POPs), such as perfluoroalkyl and polyfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), and bisphenols (BPs), have been raising global concerns due to their toxic effects on environment and human health. The monitoring of residues of POPs in seafood is crucial for assessing the accumulation of these contaminants in the study area and mitigating potential risks to human health. However, the diversity and complexity of POPs in seafood present significant challenges for their simultaneous detection. Here, a novel multi-component fluoro-functionalized covalent organic framework (OH-F-COF) was designed as SPE adsorbent for simultaneous extraction POPs. On this basis, the recognition and adsorption mechanisms were investigated by molecular simulation. Due to multiple interactions and large specific surface area, OH-F-COF displayed satisfactory coextraction performance for PFASs, PCBs, and BPs. Under optimized conditions, the OH-F-COF sorbent was employed in a strategy of simultaneous extraction and stepwise elution (SESE), in combination with HPLC-MS/MS and GC-MS method, to effectively determined POPs in seafood collected from coastal areas of China. The method obtained low detection limits for BPs (0.0037 -0.0089 ng/g), PFASs (0.0038 -0.0207 ng/g), and PCBs (0.2308 -0.2499 ng/g), respectively. This approach provided new research ideas for analyzing and controlling multitarget POPs in seafood. ENVIRONMENTAL IMPLICATIONS: Persistent organic pollutants (POPs), such as perfluoroalkyl and polyfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), and bisphenols (BPs), have caused serious hazards to human health and ecosystems. Hence, there is a need to develop a quantitative method that can rapidly detect POPs in environmental and food samples. Herein, a novel multi-component fluorine-functionalized covalent organic skeletons (OH-F-COF) were prepared at room temperature, and served as adsorbent for POPs. The SESE-SPE strategy combined with chromatographic techniques was used to achieve a rapid detection of POPs in sea foods from the coastal provinces of China. This method provides a valuable tool for analyzing POPs in environmental and food samples.

Clinical Outcomes in Type 2 Diabetes Patients After Acute Myocardial Infarction: A Comparison of Sodium-Glucose Cotransporter 2 Inhibitors vs. Non-Users.

To compare clinical outcomes in patients with type 2 diabetes (T2D) after acute myocardial infarction (AMI) using sodium-glucose cotransporter-2 inhibitors (SGLT2i) vs. non-use of SGLT2i. A national cohort study based on the Taiwan National Health Insurance Research Database enrolled 944 patients with T2D who had experienced AMI and were treated with SGLT2i and 8,941 patients who did not receive SGLT2i, respectively, from May 1, 2016, to December 31, 2019. We used propensity score matching to balance covariates across study groups. The follow-up period was from the index date to the independent occurrence of the study outcomes, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. The SGLT2i group exhibited a significantly lower incidence of cardiovascular death (0.865% per year vs. 2.048% per year; hazard ratio (HR): 0.42; 95% confidence interval (CI): 0.24-0.76; P = 0.0042), heart failure hospitalization (1.987% per year vs. 3.395% per year; HR: 0.59; 95% CI: 0.39-0.89; P = 0.0126), and all-cause mortality (3.406% per year vs. 4.981% per year, HR: 0.69; 95% CI: 0.50-0.95; P = 0.0225) compared with the non-SGLT2i group. There were no significant differences between the two groups in the incidence of AMI, ischemic stroke, coronary revascularization, major adverse cardiovascular events, composite renal outcomes, or lower limb amputation. These findings suggest that the use of SGLT2i may have favorable effects on clinical outcomes in patients with T2D after AMI.

Distinct patterns of SARS-CoV-2 BA.2.87.1 and JN.1 variants in immune evasion, antigenicity, and cell-cell fusion.

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted a comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, and spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received a bivalent mRNA vaccine booster, patients infected during the BA.2.86/JN.1-wave, and hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that BA.2.87.1 shows much less nAb escape from WT-BA.4/5 bivalent mRNA vaccination and JN.1-wave breakthrough infection sera compared to JN.1 and XBB.1.5. Interestingly, BA.2.87.1 is more resistant to neutralization by XBB.1.5-monovalent-vaccinated hamster sera than BA.2.86/JN.1 and XBB.1.5, but efficiently neutralized by a class III monoclonal antibody S309, which largely fails to neutralize BA.2.86/JN.1. Importantly, BA.2.87.1 exhibits higher levels of infectivity, cell-cell fusion activity, and furin cleavage efficiency than BA.2.86/JN.1. Antigenically, we found that BA.2.87.1 is closer to the ancestral BA.2 compared to other recently emerged Omicron subvariants including BA.2.86/JN.1 and XBB.1.5. Altogether, these results highlight immune escape properties as well as biology of new variants and underscore the importance of continuous surveillance and informed decision-making in the development of effective vaccines. IMPORTANCE: This study investigates the recently emerged SARS-CoV-2 variants, BA.2.87.1 and JN.1, in comparison to earlier variants and the parental D614G. Varied infectivity and cell-cell fusion activity among these variants suggest potential disparities in their ability to infect target cells and possibly pathogenesis. BA.2.87.1 exhibits lower nAb escape from bivalent mRNA vaccinee and BA.2.86/JN.1-infected sera than JN.1 but is relatively resistance to XBB.1.5-vaccinated hamster sera, revealing distinct properties in immune reason and underscoring the significance of continuing surveillance of variants and reformulation of vaccines. Antigenic differences between BA.2.87.1 and other earlier variants yield critical information not only for antibody evasion but also for viral evolution. In conclusion, this study furnishes timely insights into the spike biology and immune escape of the emerging variants BA.2.87.1 and JN.1, thus guiding effective vaccine development and informing public health interventions.

A Paternò-Büchi Reaction of Aromatics with Quinones under Visible Light Irradiation.

Reported herein is a Paternò-Büchi reaction of aromatic double bonds with quinones under visible light irradiation. The reactions of aromatics with quinones exposed to blue LED irradiation yielded oxetanes at -78 °C, which was attributed to both the activation of double bonds in aromatics and the stabilization of oxetanes by thiadiazole, oxadiazole, or selenadiazole groups. The addition of Cu(OTf)2 to the reaction system at room temperature resulted in the formation of diaryl ethers via the copper-catalyzed ring opening of oxetanes in situ. Notably, the substrate scope was extended to general aromatics.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.