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The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as a powerful strategy in drug design. To date, the most established method for accessing enantioenriched difluoromethyl compounds involves the enantioselective functionalization of nucleophilic and electrophilic CF₂H synthons. However, this approach is limited by lower reactivity and reduced enantioselectivity. Leveraging the unique fluorine effect, we design and synthesize a radical CF₂H synthon by incorporating isoindolinone into alkyl halides for asymmetric radical transformation. Here, we report an efficient strategy for the asymmetric construction of carbon stereocenters featuring a difluoromethyl group via nickel-catalyzed Negishi cross-coupling. This approach demonstrates mild reaction conditions and excellent enantioselectivity. Given that optically pure difluoromethylated amines and isoindolinones are key structural motifs in bioactive compounds, this strategy offers a practical solution for the efficient synthesis of CF₂H-containing chiral drug-like molecules. The difluoromethyl group is a crucial fluorinated moiety, and the synthesis of chiral CF₂H-containing analogs is a powerful strategy in drug design and screening. Here, the authors report a strategy for the asymmetric construction of carbon stereocenters featuring a difluoromethyl group via nickel-catalyzed Negishi cross-coupling.

Uncontrollable dendrite growth and unstable interface chemistry between the electrode and electrolyte seriously hinder the practical application of potassium metal batteries (PMBs). Herein, a functional intermediate medium comprising molybdenum carbide decorated N‐doped carbon (MoC/NC) is designed to preferentially and strongly interact with the KFSI molecules, which causes localized charge rearrangements on its surface and the formation of electron‐rich microdomains. It promotes the local accumulation of K+ and induces an anions dominant solvation structure, ultimately achieving the construction of SEI rich in inorganic components such as KF. The derived SEI layer effectively suppresses the electron tunneling effect because of the electronic insulation of KF, while the integrated MoC/NC functional intermediate medium facilitates the rapid and balanced K+/electron diffusion due to its intrinsic high ionic conductivity. Benefiting from this interfacial synergy, the integrated electrode (MoC/NC@K) exhibits significantly boosted interfacial transport kinetic and uniform potassium deposition behavior. The symmetric cell demonstrates a stable cycling for more than 800 h at 0.5 mA cm−2, and the cycle stability is also enhanced in the full cells. This work presents innovative concepts and approaches for precisely regulating interface components in PMBs by a multi‐scale strategy of molecules and interfaces. A MoC/NC functional intermediate medium preferentially interacts with KFSI to reconstruct the interfacial solvation structure and form a KF‐rich inorganic SEI. The synergistic integration of the electronically insulating SEI and MoC/NC suppresses electron tunneling, enables fast and balanced K+/electron transport, and promotes uniform K deposition for long‐life potassium metal batteries.

Circulating tumor DNA (ctDNA) has been recognized as a promising tumor-specific biomarker, but its molecular features in peripheral T cell lymphoma (PTCL) have not been well explored. We investigated the translational significance of liquid biopsy in a uniformly treated PTCL cohort (N=64). Our study found that pretreatment ctDNA burden was strongly associated with clinical risk factors and identified as a superior predictor of progression-free survival and overall survival. Although 46.9% of patients achieved complete response at the end of therapy (EOT), only 25.9% achieved negative minimal residual disease (MRDend-) and demonstrated superior prognosis. These findings suggests that MRD status at EOT may be a critical factor in disease progression and recurrence for PTCL patients. Additionally, the most frequently altered genes were identified as TET2 (6.7%), DNMT3A (48.5%), RHOA (27.3%), and TP53 (15.2%), which were not cleared by first-line CHOP-like regimens. Most importantly, clonal evolution was displayed during induction therapy and follow-up across all histological subtypes of PTCL patients. These findings support that EOT MRD status could serve as an important prognostic marker for PTCL patients and clear the direction of exploration and selection the new drugs particularly targeted to TET2/DNMT3A/RHOA mutation integrating with conventional treatments for PTCL patients. Key points Only approximately 26% of patients achieved EOT MRD clearance, which might be a critical factor for disease progression and recurrence for PTCL patients. Clonal evolution was displayed during first-line CHOP-like regimen therapy and follow-up across all histological subtypes of PTCL patients.

We report here the identification of the key sites for the beta structure motifs of the islet amyloid polypeptide (IAPP) analogs by using scanning tunneling microscopy (STM). Duplex folding structures in human IAPP8–37 (hIAPP8–37) assembly were observed featuring a hairpin structure. The multiplicity in rIAPP assembly structures indicates the polydispersity of the rat IAPP8–37 (rIAPP8–37) beta-like motifs. The bimodal length distribution of beta structure motifs for rIAPP8–37 R18H indicates the multiple beta segments linked by turns. The IAPP8–37 analogs share common structure motifs of IAPP8–17 and IAPP26–37 with the most probable key sites at positions around Ser19/Ser20 and Gly24. These observations reveal the similar amyloid formation tendency in the C and N terminus segments because of the sequence similarity, while the differences in specific amino acids at each key site manifest the effect of sequence variations. The results could be beneficial for studying structural polymorphism of amyloidal peptides with multiple beta structure motifs.

This paper presents a dual-mode low-density parity-check (LDPC) decoding architecture that has excellent error-correcting capability and a high parallelism design for fifth-generation (5G) new-radio (NR) applications. We adopted a high parallelism design using a layered decoding schedule to meet the high throughput requirement of 5G NR systems. Although the increase in parallelism can efficiently enhance the throughput, the hardware implementation required to support high parallelism is a significant hardware burden. To efficiently reduce the hardware burden, we used a grouping search rather than a sorter, which was used in the minimum finder with decoding performance loss. Additionally, we proposed a compensation scheme to improve the decoding performance loss by revising the probabilistic second minimum of a grouping search. The post-layout implementation of the proposed dual-mode LDPC decoder is based on the Taiwan Semiconductor Manufacturing Company (TSMC) 40 nm complementary metal-oxide-semiconductor (CMOS) technology, using a compensation scheme of grouping comparison for 5G communication systems with a working frequency of 294.1 MHz. The decoding throughput achieved was at least 10.86 Gb/s without evaluating early termination, and the decoding power consumption was 313.3 mW.

Potassium-ion batteries (PIBs) have garnered significant interest due to their abundant resources, wide distribution and low price, emerging as an ideal alternative to lithium-ion batteries for energy storage systems. As one of the key components, anode materials act as a crucial role in the specific capacity, energy density, power density and service life of PIBs, so it is highly significant to conduct a comprehensive investigation on them. Carbon materials are widely employed as the anode for PIBs because of their advantages of environmental friendliness, abundant raw materials and diverse structures. According to the structural differences, carbon materials are mainly distinguished as crystalline carbon represented by graphite and graphene, and soft carbon and hard carbon existing in amorphous state. Different types of carbon materials have special ion storage mechanisms, storage capacity and cycling stability. Herein, it is meaningful to summarize and discuss the characteristics and research progress in carbon anode materials for PIBs in recent years. Firstly, according to the development status and application prospect of graphite, graphene, soft carbon, and hard carbon, we deeply generalize the electrochemical performance and potassium storage mechanism. Then we dig out the key problems faced by different carbon materials and arrange various modification design and solving strategies of novel carbon anodes. Finally, we expound the importance of carbon anode materials as the anode and PIBs, explore the application potential of current and emerging carbon anode materials, and put forward some suggestions and prospects for the future development of carbon materials.

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3 , and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.

The CRISPR/Cas9 system is an efficient gene-editing method, but the majority of gene-edited animals showed mosaicism, with editing occurring only in a portion of cells. Here we show that single gene or multiple genes can be completely knocked out in mouse and monkey embryos by zygotic injection of Cas9 mRNA and multiple adjacent single-guide RNAs （spaced 10-200 bp apart） that target only a single key exon of each gene. Phenotypic analysis of F0 mice following targeted deletion of eight genes on the Y chromosome individually demonstrated the robustness of this approach in generating knockout mice. Importantly, this approach delivers complete gene knockout at high efficien- cies （100% on Arnt[ and 91% on Prrt2） in monkey embryos. Finally, we could generate a complete Prrt2 knockout monkey in a single step, demonstrating the usefulness of this approach in rapidly establishing gene-edited monkey models.

The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as a powerful strategy in drug design. To date, the most established method for accessing enantioenriched difluoromethyl compounds involves the enantioselective functionalization of nucleophilic and electrophilic CF₂H synthons. However, this approach is limited by lower reactivity and reduced enantioselectivity. Leveraging the unique fluorine effect, we design and synthesize a radical CF₂H synthon by incorporating isoindolinone into alkyl halides for asymmetric radical transformation. Here, we report an efficient strategy for the asymmetric construction of carbon stereocenters featuring a difluoromethyl group via nickel-catalyzed Negishi cross-coupling. This approach demonstrates mild reaction conditions and excellent enantioselectivity. Given that optically pure difluoromethylated amines and isoindolinones are key structural motifs in bioactive compounds, this strategy offers a practical solution for the efficient synthesis of CF₂H-containing chiral drug-like molecules.

Because of weak dissipation effects, swells generated by fierce storms can propagate across an entire ocean basin; therefore, observing swell generation and decay and retrieving storm characteristics from a swell by satellite remote sensing are possible. In this study, based on the dispersion relation and geometrical optics principle, we used SAR wave mode data from 2003 to 2010 provided by GlobWave to track swells with peak wavelengths of more than 300 m to locate a storm-generated far-traveling swell and present the swell field related to this ＂static＂ origin. Through a comparison with ECMWF wind datasets, we conducted validations and explored some conditions that cause misjudgments in swell origins. Finally, we obtained the spatiotemporal distribution characteristics of satellite-observed swell origins （i.e., the fierce wind condition） and their evolution. This work can be used as a reference for wave models, providing early swell warnings, determining air-sea surface interactions, and determining global climate change.