Fabrication-induced even-odd discrepancy of magnetotransport in few-layer MnBi2Te4.

The van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.

Optically pumped flexible GaN-based ultraviolet VCSELs.

Flexible optoelectronic platforms, which integrate optoelectronic devices on a flexible substrate, are promising in more complex working environments benefiting from the mechanical flexibility. Herein, for the first time to the best of our knowledge, a flexible GaN-based vertical cavity surface-emitting laser (VCSEL) in the ultraviolet A (UVA) range was demonstrated by using a thin-film transfer process based on laser lift-off (LLO) and spin-coating of a flexible substrate. The lasing wavelength is 376.5 nm with a linewidth of 0.6 nm and threshold energy of 98.4 nJ/pulse, corresponding to a threshold energy density of 13.9 mJ/cm2. The flexible substrate in this study is directly formed by spin-coating of photosensitive epoxy resin, which is much simplified and cost-effective, and a 2-in. wafer scale GaN-based membrane can be successfully transferred to a flexible substrate through this method. Such flexible UVA VCSELs are promising for the development of next-generation flexible and wearable technologies.

Pectate lyase genes from Radopholus similis and their application in pathotype identification.

Radopholus similis is a destructive, migratory, and endophytoparasitic nematode. It has two morphologically indistinguishable pathotypes (or physiological races): banana and citrus pathotypes. At present, the only reliable method to differentiate the two pathotypes is testing the infestation and parasitism of nematodes on Citrus spp. via inoculation. However, differences in inoculation methods and conditions adopted by different researchers complicate obtaining consistent results. In this study, the parasitism and pathogenicity of 10 R. similis populations on rough lemon (Citrus limon) seedlings and the tropism and invasion of rough lemon roots were tested. It revealed that populations SWK, GJ, FZ, GZ, DBSR, and YJ were citrus pathotypes, which showed parasitism and pathogenicity on rough lemon and could invade rough lemon roots, whereas populations XIN, ML, HN6, and HL were banana pathotypes, having no parasitism and pathogenicity on rough lemon and they did not invade the rough lemon roots. Four pectate lyase genes (Rs-pel-2, Rs-pel-3, Rs-pel-4, and Rs-pel-5) belonging to the Class III family from these populations were amplified and analysed. The gene Rs-pel-3 could be amplified from six citrus pathotype populations and was stably expressed in the four developmental stages of the nematode, whereas it could not be amplified from the four banana pathotypes. Rs-pel-3 expression may be related to the parasitism and pathogenicity of R. similis on rough lemon. Hence, it can be used as a molecular marker to distinguish between banana and citrus pathotypes and as a target gene for the molecular identification of these two pathotypes. KEY POINTS: • Four pectate lyase genes (Rs-pels) from Radopholus similis were cloned and analysed. • The expression of Rs-pels is different in two pathotypes of Radopholus similis. • A molecular identification method for two pathotypes of Radopholus similis using pectate lyase gene Rs-pel-3 as the target gene was established.

miR-1246 promotes osteosarcoma cell migration via NamiRNA-enhancer network dependent on Argonaute 2.

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR-1246 levels. Specially, miR-1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR-1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR-1246 in vivo. Collectively, our findings suggest that miR-1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA-targeted gene activation and the potential of miR-1246 for osteosarcoma metastasis therapy.

Machine learning-based integration develops a stress response stated T cell (Tstr)-related score for predicting outcomes in clear cell renal cell carcinoma.

BACKGROUND: Establishment of a reliable prognostic model and identification of novel biomarkers are urgently needed to develop precise therapy strategies for clear cell renal cell carcinoma (ccRCC). Stress response stated T cells (Tstr) are a new T-cell subtype, which are related to poor disease stage and immunotherapy response in various cancers. METHODS: 10 machine-learning algorithms and their combinations were applied in this work. A stable Tstr-related score (TCs) was constructed to predict the outcomes and PD-1 blockade treatment response in ccRCC patients. A nomogram based on TCs for personalized prediction of patient prognosis was constructed. Functional enrichment analysis and TimiGP algorithm were used to explore the underlying role of Tstr in ccRCC. The key TCs-related gene was identified by comprehensive analysis, and the bioinformatics results were verified by immunohistochemistry using a tissue microarray. RESULTS: A robust TCs was constructed and validated in four independent cohorts. TCs accurately predicted the prognosis and PD-1 blockade treatment response in ccRCC patients. The novel nomogram was able to precisely predict the outcomes of ccRCC patients. The underlying biological process of Tstr was related to acute inflammatory response and acute-phase response. Mast cells were identified to be involved in the role of Tstr as a protective factor in ccRCC. TNFS13B was shown to be the key TCs-related gene, which was an independent predictor of unfavorable prognosis. The protein expression analysis of TNFSF13B was consistent with the mRNA analysis results. High expression of TNFSF13B was associated with poor response to PD-1 blockade treatment. CONCLUSIONS: This study provides a Tstr cell-related score for predicting outcomes and PD-1 blockade therapy response in ccRCC. Tstr cells may exert their pro-tumoral role in ccRCC, acting against mast cells, in the acute inflammatory tumor microenvironment. TNFSF13B could serve as a key biomarker related to TCs.

Liver-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab for advanced hepatocellular carcinoma: a retrospective observational study of 23 cases.

Background: Programmed cell death protein 1 (PD-1) or its ligand (PD-L1) monoclonal antibody combined with bevacizumab (a monoclonal antibody targeting vascular endothelial growth factor) has been established as first-line systemic treatment for advanced hepatocellular carcinoma (HCC). Radiotherapy is a crucial local treatment for HCC. Mutual efficacy enhancement has been reported between radiotherapy, anti-angiogenesis therapy and immunotherapy in preclinical researches, but not been validated in clinical practice. Whether radiotherapy can enhance efficacy of anti-PD-1 immunotherapy plus bevacizumab for HCC remains unclear. This retrospective observational study aimed to appraise efficacy and safety of the combination of radiotherapy with pembrolizumab (a PD-1 monoclonal antibody) and bevacizumab for advanced HCC for the first time. Methods: Patients with advanced HCC treated by intrahepatic tumor-directed moderately hypo-fractionated radiotherapy combined with pembrolizumab and bevacizumab were consecutively included. Clinicopathological characteristics, therapeutic outcomes and treatment-related adverse events (TRAEs) were recorded and evaluated. Results: A total of 23 patients were eventually enrolled. Median cycles of pembrolizumab and bevacizumab were 4 (median, 1-8) and 4 (median, 1-9) cycles. The objective response rates and disease control rates of irradiated intrahepatic HCC and non-irradiated extrahepatic HCC were 34.8% [95% confidence interval (CI), 16.4-57.3%] vs. 10.0% (95% CI, 1.2-31.7%), and 91.3% (95% CI, 72.0-98.9%) vs. 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.6 (95% CI, 4.7-8.5) and 18.3 (95% CI, 8.2-33.6) months, and 12-month PFS and OS rates were 17.5% (95% CI, 7.0-28.0%) and 60.9% (95% CI, 50.7-71.1%). Two patients (8.7%) with locally advanced, unresectable HCC eventually underwent curative resection of tumors after this trimodal treatment. Eighteen patients (78.3%) had ≥ grade 3 TRAEs, with myelosuppression and transaminase increase as the most common. Conclusions: This study firstly reported that combining radiotherapy with pembrolizumab and bevacizumab was preliminarily a feasible and effective therapeutic choice for advanced HCC in despite of more TRAEs. This tri-modal regimen may be a potential conversion therapy for unresectable, locally advanced HCC. The limitations of this study are its retrospective nature and small sample size; therefore, big-sample prospective studies are warranted to further investigate this tri-modal regimen.

Study on the Characteristics of Circumferential and Longitudinal Flow of Vault Concrete during Tunnel Lining Pouring Processes.

With a large number of railroad and highway tunnels opening for operation, the diseases caused by hidden lining defects are increasing. The study of flow characteristics of freshly mixed concrete during tunnel lining casting is the key to revealing the formation mechanism of hidden defects. This paper revealed the location of blank lining formation by investigating the circumferential and longitudinal flow characteristics of concrete in the vault during tunnel pouring to provide suggestions for improving the quality of tunnel lining pouring for the various projects. This paper adopted the method of indoor testing, selected the suitable working conditions and flow parameters, validated the accuracy of the test with a numerical simulation, and simulated the secondary lining pouring process of the tunnel arch from the circumferential direction and longitudinal direction. This revealed the flow characteristics of the freshly mixed concrete in the process of pouring the arch lining. The flow of concrete in the arch lining was basically characterized by two major features which were similar to the flow in the pumping pipe and the layered flow. It also revealed the relationship between the concrete flow rate, flow distance, and the location of the formation of the blank lining risk zone with the slump of the concrete, the pumping pressure, and the radius of the tunnel.

Selective-Area-Grown PbTe-Pb Planar Josephson Junctions for Quantum Devices.

Planar Josephson junctions are predicted to host Majorana zero modes. The material platforms in previous studies are two-dimensional electron gases (InAs, InSb, InAsSb, and HgTe) coupled to a superconductor such as Al or Nb. Here, we introduce a new material platform for planar JJs, the PbTe-Pb hybrid. The semiconductor, PbTe, was grown as a thin film via selective area epitaxy. The Josephson junction was defined by a shadow wall during the deposition of superconductor Pb. Scanning transmission electron microscopy reveals a sharp semiconductor-superconductor interface. Gate-tunable supercurrents and multiple Andreev reflections are observed. A perpendicular magnetic field causes interference patterns of the switching current, exhibiting Fraunhofer-like and SQUID-like behaviors. We further demonstrate a prototype device for Majorana detection wherein phase bias and tunneling spectroscopy are applicable.

The mechanism of curcumin to protect mouse ovaries from oxidative damage by regulating AMPK/mTOR mediated autophagy.

BACKGROUND: Oxidative stress is considered the main cause of granulosa cell apoptosis in ovarian disease. Curcumin has various biological roles, but its potential role in protecting granulosa cells from oxidative damage remains unidentified. PURPOSE: The study revealed the protective effect of curcumin on granulosa cell survival under oxidative stress, and explored its mode of action. STUDY DESIGN: The protective effect of curcumin on oxidative stress-induced ovarian cell apoptosis was evaluated in vivo and in vitro, and the role of autophagy and AMPK/mTOR signaling pathway in this process was also demonstrated. METHODS: First, mice were injected to 3-nitropropionic acid (3-NPA, 20 mg/kg/day) for 14 consecutive days to establish the ovarian oxidative stress model, at same time, curcumin (50, 100, 200 mg/kg/day) was given orally. Thereafter, functional changes, cell apoptosis, and autophagy in ovarian tissue were evaluated by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, western blotting, TUNEL assays, and transmission electron microscopy. Finally, oxidative stress model of granulosa cells was established with H2O2in vitro and treated with curcumin. The underlying mechanisms of curcumin to protect the apoptosis under oxidative stress in vitro were determined using western blotting and TUNEL assays. RESULTS: In our study, after curcumin treatment, the mouse ovarian function disorder under 3-nitropropionic acid-induced oxidative stress recovered significantly, and ovarian cell apoptosis decreased. H2O2 induced granulosa cell apoptosis in vitro, and curcumin antagonized this process. Autophagy contributes to tissue and cell survival under stress. We therefore examined the role of autophagy in this process. According to the in vivo and in vitro results, curcumin restored autophagy under oxidative stress. The autophagy inhibitor (chloroquine) exhibited the same effect as curcumin, whereas the autophagy activator (rapamycin) antagonized the effect of curcumin. In addition, the study found that the AMPK/mTOR pathway plays a crucial role in curcumin- mediated autophagy to protect against oxidative stress-induced apoptosis. CONCLUSION: Our findings for the first time systematically revealed a new mechanism through which curcumin protects ovarian granulosa cells from oxidative stress-induced damage through AMPK/mTOR-mediated autophagy and suggested that it can be a new therapeutic direction for female ovarian diseases.

Fe-N co-doped biochar derived from biomass waste triggers peracetic acid activation for efficient water decontamination.

In this study, the porous carbon material (FeN-BC) with ultra-high catalytic activity was obtained from waste biomass through Fe-N co-doping. The prominent degradation rate (> 96.8%) of naproxen (NAP) was achieved over a wide pH range (pH 3.0-9.0) in FeN-BC/PAA system. Unlike previously reported iron-based peracetic acid (PAA) systems with •OH or RO• as the dominated reactive species, the degradation of contaminants was attributed to singlet oxygen (1O2) produced by organic radicals (RO•) decomposition, which was proved to be thermodynamically feasible and favorable by theoretical calculations. Combining the theoretical calculations, characteristic and experimental analysis, the synergistic effects of Fe and N were proposed and summarized as follows: i) promoted the formation of extensive defects and Fe0 species that facilitated electron transfer between FeN-BC and PAA and continuous Fe(II) generation; ii) modified the specific surface area (SSA) and the isoelectric point of FeN-BC in favor of PAA adsorption on the catalyst surface. This study provides a strategy for waste biomass reuse to construct a heterogeneous catalyst/PAA system for efficient water purification and reveals the synergistic effects of typical metal-heteroatom for PAA activation.

Relationships between rumination and different types of rapid eye movement sleep in patients with chronic insomnia disorder.

BACKGROUND AND OBJECTIVE: Rumination, a common factor of chronic insomnia disorder (CID) caused by cognitive-emotional arousal, is associated with an increased amount of rapid eye movement (REM) sleep. However, the specific subtypes, such as phasic REM and tonic REM, that contribute to the increased REM sleep have not been reported. This study aimed to determine the association between rumination and different REM sleep subtypes in patients with CID. METHODS: This study enrolled 35 patients with CID and 27 age- and sex-matched healthy controls. The Immersion-Rumination Questionnaire evaluated participants' rumination, and the Insomnia Severity Index was used to assess insomnia severity. Finally, polysomnography was used to monitor objective sleep quality and quantification of different types of REM. RESULTS: The CID patients had higher rumination scores than the healthy controls. They had a shorter REM sleep duration, less phasic REM, a lower percentage of phasic REM time, and a higher percentage of tonic REM time. Spectral analysis revealed that the patients affected by insomnia had higher ß power during REM sleep, higher ß and σ power during phasic REM sleep, and higher ß, and γ power during tonic REM sleep. Partial correlation analysis showed that rumination in the CID patients correlated negatively with the duration of phasic REM sleep. Additionally, rumination correlated negatively with δ power in REM sleep and positively with ß power in REM sleep, tonic REM sleep, phasic REM sleep, N3and N2 sleep in the patients with CID. CONCLUSION: The CID patients had stronger rumination, reduced total and phasic REM sleep, and the stronger rumination was, the shorter phasic REM was and the higher fast (ß) wave power in REM sleep.

A chimeric porcine reproductive and respiratory syndrome virus 1 strain containing synthetic ORF2-6 genes can trigger T follicular helper cell and heterologous neutralizing antibody responses and confer enhanced cross-protection.

The prevalence of porcine reproductive and respiratory syndrome virus 1 (PRRSV1) isolates has continued to increase in Chinese swine herds in recent years. However, no effective control strategy is available for PRRSV1 infection in China. In this study, we generated the first infectious cDNA clone (rHLJB1) of a Chinese PRRSV1 isolate and subsequently used it as a backbone to construct an ORF2-6 chimeric virus (ORF2-6-CON). This virus contained a synthesized consensus sequence of the PRRSV1 ORF2-6 gene encoding all the envelope proteins. The ORF2-6 consensus sequence shared > 90% nucleotide similarity with four representative strains (Amervac, BJEU06-1, HKEU16 and NMEU09-1) of PRRSV1 in China. ORF2-6-CON had replication efficacy similar to that of the backbone rHLJB1 virus in primary alveolar macrophages (PAMs) and exhibited cell tropism in Marc-145 cells. Piglet inoculation and challenge studies indicated that ORF2-6-CON is not pathogenic to piglets and can induce enhanced cross-protection against a heterologous SD1291 isolate. Notably, ORF2-6-CON inoculation induced higher levels of heterologous neutralizing antibodies (nAbs) against SD1291 than rHLJB1 inoculation, which was concurrent with a higher percentage of T follicular helper (Tfh) cells in tracheobronchial lymph nodes (TBLNs), providing the first clue that porcine Tfh cells are correlated with heterologous PRRSV nAb responses. The number of SD1291-strain-specific IFNγ-secreting cells was similar in ORF2-6-CON-inoculated and rHLJB1-inoculated pigs. Overall, our findings support that the Marc-145-adapted ORF2-6-CON can trigger Tfh cell and heterologous nAb responses to confer improved cross-protection and may serve as a candidate strain for the development of a cross-protective PRRSV1 vaccine.

Case report: Neglected subacute thyroiditis: a case following COVID-19 vaccination.

We report a case of overlooked Subacute Thyroiditis (SAT) potentially induced by the administration of a COVID-19 vaccine. This case prompted a thorough review of the existing literature to elucidate possible mechanisms by which immune responses to the COVID-19 vaccine might precipitate thyroid damage. The primary objective is to enhance the clinical understanding and awareness of SAT among healthcare professionals. Subacute thyroiditis is a prevalent form of self-limiting thyroid disorder characterized by fever, neck pain or tenderness, and palpitations subsequent to viral infection. The development of numerous SARS-CoV-2 vaccines during the COVID-19 pandemic was intended to mitigate the spread of the virus. Nevertheless, there have been documented instances of adverse reactions arising from SARS-CoV-2 vaccines, such as the infrequent occurrence of subacute thyroiditis. While the majority of medical practitioners can discern classic subacute thyroiditis, not all cases exhibit typical characteristics, and not all systematic treatments yield positive responses. In this study, we present a rare case of subacute thyroiditis linked to the administration of the SARS-CoV-2 vaccine. A previously healthy middle-aged female developed fever and sore throat 72 h post-inoculation with the inactivated SARS-CoV-2 vaccine. Initially attributing these symptoms to a common cold, she self-administered ibuprofen, which normalized her body temperature but failed to alleviate persistent sore throat. Suspecting a laryngopharyngeal disorder, she sought treatment from an otolaryngologist. However, the pain persisted, accompanied by intermittent fever over several days. After an endocrinology consultation, despite the absence of typical neck pain, her examination revealed abnormal thyroid function, normal thyroid antibodies, heterogeneous echogenicity on thyroid ultrasonography, and elevated levels of Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP). These findings led to a consideration of the diagnosis of SAT. Initially, she was treated with non-steroidal anti-inflammatory drugs (NSAIDs) for her fever, which proved effective, but her neck pain remained uncontrolled. This suggested a poor response to NSAIDs. Consequently, steroid therapy was initiated, after which her symptoms of fever and neck pain rapidly resolved.

Palladium-catalyzed denitrogenation/vinylation of benzotriazinones with vinylene carbonate.

Herein, a novel Pd-catalyzed denitrogenation/vinylation of benzotriazinones using vinylene carbonate as the vinylation reagent is reported. This transformation demonstrates an unprecedented skeletal editing approach, effectively converting NN to CC fragments in situ and synthesizing a collection of isoquinolinones with broad-spectrum functional group tolerance. Moreover, the quite concise reaction system and late-stage modification of bioactive molecules comprehensively underscore the practical potential of this protocol.

Sub-2 nm IrRuNiMoCo High-Entropy Alloy with Iridium-Rich Medium-Entropy Oxide Shell to Boost Acidic Oxygen Evolution.

Ensuring high catalytic activity and durability at low iridium (Ir)usage is still a big challenge for the development of electrocatalysts toward oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE). Here, a rapid liquid-reduction combined with surface galvanic replacement strategy is reported to synthesize the sub 2 nm high-entropy alloy (HEA) nanoparticles featured with Ir-rich IrRuNiMo medium-entropy oxide shell (Ir-MEO) and a IrRuCoNiMo HEA core (HEA@Ir-MEO). Advanced spectroscopies reveal that the Ir-rich MEO shell inhibits the severe structural evolution of transition metals upon the OER, thus guaranteeing the structural stability. In situ differential electrochemical mass spectrometry, activation energy analysis and theoretical calculations unveil that the OER on HEA@Ir-MEO follows an adsorbate evolution mechanism pathway, where the energy barrier of rate-determining step is substantially lowered. The optimized catalyst delivers the excellent performance (1.85 V/3.0 A cm-2@80 °C), long-term stability (>500 h@1.0 Acm-2), and low energy consumption (3.98 kWh Nm-3 H2 @1.0 A cm-2) in PEMWE with low Ir usage of ≈0.4 mg cm-2, realizing the dramatical reduction of hydrogen (H2) production cost to 0.88 dollar per kg (H2).

Metagenomic evidence for antibiotic-associated actinomycetes in the Karamay Gobi region.

Due to the misuse of antibiotics, there is an increasing emergence and spread of multidrug-resistant (MDR) bacteria, leading to a human health crisis. To address clinical antibiotic resistance and prevent/control pathogenic microorganisms, the development of novel antibiotics is essential. This also offers a new approach to discovering valuable actinobacterial flora capable of producing natural bioactive products. In this study, we employed bioinformatics and macro-genome sequencing to collect 15 soil samples from three different locations in the Karamay Gobi region. First, we assessed the diversity of microorganisms in soil samples from different locations, analyzing the content of bacteria, archaea, actinomycetes, and fungi. The biodiversity of soil samples from outside the Gobi was found to be higher than that of soil samples from within and in the center of the Gobi. Second, through microbial interaction network analysis, we identified actinomycetes as the dominant group in the system. We have identified the top four antibiotic genes, such as Ecol_fabG_TRC, Efac_liaR_DAP, tetA (58), and macB, by CARD. These genes are associated with peptide antibiotics, disinfecting agents and antiseptics, tetracycline antibiotics, and macrolide antibiotics. In addition, we also obtained 40 other antibiotic-related genes through CARD alignment. Through in-depth analysis of desert soil samples, we identified several unstudied microbial species belonging to different families, including Erythrobacteriaceae, Solirubrobacterales, Thermoleophilaceae, Gaiellaceae, Nocardioidaceae, Actinomycetia, Egibacteraceae, and Acidimicrobiales. These species have the capability to produce peptide antibiotics, macrolide antibiotics, and tetracycline antibiotics, as well as disinfectants and preservatives. This study provides valuable theoretical support for future in-depth research.

Construction of Phosphorothiolated 2-Pyrrolidinones via Photoredox/Copper-Catalyzed Cascade Radical Cyclization/Phosphorothiolation.

A photoredox/copper-catalyzed cascade radical cyclization/phosphorothiolation reaction of N-allylbromoacetamides and P(O)SH compounds has been established. A broad range of novel nonfluorine- or difluoro-substituted 2-pyrrolidinones bearing the C(sp3)-SP(O)(OR)2 moiety can be conveniently constructed in moderate to good yields under mild conditions. Importantly, most of the tested phosphorothiolated 2-pyrrolidinones showed potent inhibitory effects toward both AChE and BChE.

Steering lithium and potassium storage mechanism in covalent organic frameworks by incorporating transition metal single atoms.

Organic electrodes mainly consisting of C, O, H, and N are promising candidates for advanced batteries. However, the sluggish ionic and electronic conductivity limit the full play of their high theoretical capacities. Here, we integrate the idea of metal-support interaction in single-atom catalysts with π-d hybridization into the design of organic electrode materials for the applications of lithium (LIBs) and potassium-ion batteries (PIBs). Several types of transition metal single atoms (e.g., Co, Ni, Fe) with π-d hybridization are incorporated into the semiconducting covalent organic framework (COF) composite. Single atoms favorably modify the energy band structure and improve the electronic conductivity of COF. More importantly, the electronic interaction between single atoms and COF adjusts the binding affinity and modifies ion traffic between Li/K ions and the active organic units of COFs as evidenced by extensive in situ and ex situ characterizations and theoretical calculations. The corresponding LIB achieves a high reversible capacity of 1,023.0 mA h g-1 after 100 cycles at 100 mA g-1 and 501.1 mA h g-1 after 500 cycles at 1,000 mA g-1. The corresponding PIB delivers a high reversible capacity of 449.0 mA h g-1 at 100 mA g-1 after 150 cycles and stably cycled over 500 cycles at 1,000 mA g-1. This work provides a promising route to engineering organic electrodes.

Non-viral Gene Therapy for Melanoma Using Lysenin from Eisenia Foetida.

Earthworms, long utilized in traditional medicine, serve as a source of inspiration for modern therapeutics. Lysenin, a defensive factor in the coelom fluid of the earthworm Eisenia fetida, has multiple bioactivities. However, the inherent toxicity of Lysenin as a pore-forming protein (PFP) restricts its application in therapy. Here, a gene therapy strategy based on Lysenin for cancer treatment is presented. The formulation consists of polymeric nanoparticles complexed with the plasmid encoding Lysenin. After transfection in vitro, melanoma cells can express Lysenin, resulting in necrosis, autophagy, and immunogenic cell death. The secretory signal peptide alters the intracellular distribution of the expressed product of Lysenin, thereby potentiating its anticancer efficacy. The intratumor injection of Lysenin gene formulation can efficiently kill the transfected melanoma cells and activate the antitumor immune response. Notably, no obvious systemic toxicity is observed during the treatment. Non-viral gene therapy based on Lysenin derived from Eisenia foetida exhibits potential in cancer therapy, which can inspire future cancer therapeutics.