Ligand-channel-enabled ultrafast Li-ion conduction.

Li-ion batteries (LIBs) for electric vehicles and aviation demand high energy density, fast charging and a wide operating temperature range, which are virtually impossible because they require electrolytes to simultaneously have high ionic conductivity, low solvation energy and low melting point and form an anion-derived inorganic interphase1-5. Here we report guidelines for designing such electrolytes by using small-sized solvents with low solvation energy. The tiny solvent in the secondary solvation sheath pulls out the Li+ in the primary solvation sheath to form a fast ion-conduction ligand channel to enhance Li+ transport, while the small-sized solvent with low solvation energy also allows the anion to enter the first Li+ solvation shell to form an inorganic-rich interphase. The electrolyte-design concept is demonstrated by using fluoroacetonitrile (FAN) solvent. The electrolyte of 1.3 M lithium bis(fluorosulfonyl)imide (LiFSI) in FAN exhibits ultrahigh ionic conductivity of 40.3 mS cm-1 at 25 °C and 11.9 mS cm-1 even at -70 °C, thus enabling 4.5-V graphite||LiNi0.8Mn0.1Co0.1O2 pouch cells (1.2 Ah, 2.85 mAh cm-2) to achieve high reversibility (0.62 Ah) when the cells are charged and discharged even at -65 °C. The electrolyte with small-sized solvents enables LIBs to simultaneously achieve high energy density, fast charging and a wide operating temperature range, which is unattainable for the current electrolyte design but is highly desired for extreme LIBs. This mechanism is generalizable and can be expanded to other metal-ion battery electrolytes.

Controlling the helicity of light by electrical magnetization switching.

Controlling the intensity of emitted light and charge current is the basis of transferring and processing information1. By contrast, robust information storage and magnetic random-access memories are implemented using the spin of the carrier and the associated magnetization in ferromagnets2. The missing link between the respective disciplines of photonics, electronics and spintronics is to modulate the circular polarization of the emitted light, rather than its intensity, by electrically controlled magnetization. Here we demonstrate that this missing link is established at room temperature and zero applied magnetic field in light-emitting diodes2-7, through the transfer of angular momentum between photons, electrons and ferromagnets. With spin-orbit torque8-11, a charge current generates also a spin current to electrically switch the magnetization. This switching determines the spin orientation of injected carriers into semiconductors, in which the transfer of angular momentum from the electron spin to photon controls the circular polarization of the emitted light2. The spin-photon conversion with the nonvolatile control of magnetization opens paths to seamlessly integrate information transfer, processing and storage. Our results provide substantial advances towards electrically controlled ultrafast modulation of circular polarization and spin injection with magnetization dynamics for the next-generation information and communication technology12, including space-light data transfer. The same operating principle in scaled-down structures or using two-dimensional materials will enable transformative opportunities for quantum information processing with spin-controlled single-photon sources, as well as for implementing spin-dependent time-resolved spectroscopies.

A LaCl3-based lithium superionic conductor compatible with lithium metal.

Inorganic superionic conductors possess high ionic conductivity and excellent thermal stability but their poor interfacial compatibility with lithium metal electrodes precludes application in all-solid-state lithium metal batteries1,2. Here we report a LaCl3-based lithium superionic conductor possessing excellent interfacial compatibility with lithium metal electrodes. In contrast to a Li3MCl6 (M = Y, In, Sc and Ho) electrolyte lattice3-6, the UCl3-type LaCl3 lattice has large, one-dimensional channels for rapid Li+ conduction, interconnected by La vacancies via Ta doping and resulting in a three-dimensional Li+ migration network. The optimized Li0.388Ta0.238La0.475Cl3 electrolyte exhibits Li+ conductivity of 3.02 mS cm-1 at 30 °C and a low activation energy of 0.197 eV. It also generates a gradient interfacial passivation layer to stabilize the Li metal electrode for long-term cycling of a Li-Li symmetric cell (1 mAh cm-2) for more than 5,000 h. When directly coupled with an uncoated LiNi0.5Co0.2Mn0.3O2 cathode and bare Li metal anode, the Li0.388Ta0.238La0.475Cl3 electrolyte enables a solid battery to run for more than 100 cycles with a cutoff voltage of 4.35 V and areal capacity of more than 1 mAh cm-2. We also demonstrate rapid Li+ conduction in lanthanide metal chlorides (LnCl3; Ln = La, Ce, Nd, Sm and Gd), suggesting that the LnCl3 solid electrolyte system could provide further developments in conductivity and utility.

Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Daratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed. METHODS: In this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group). The primary end point was progression-free survival. Key secondary end points were a complete response or better and minimal residual disease (MRD)-negative status. RESULTS: At a median follow-up of 47.5 months, the risk of disease progression or death in the D-VRd group was lower than the risk in the VRd group. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for disease progression or death, 0.42; 95% confidence interval, 0.30 to 0.59; P<0.001); the P value crossed the prespecified stopping boundary (P = 0.0126). The percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group (87.9% vs. 70.1%, P<0.001), as was the percentage of patients with MRD-negative status (75.2% vs. 47.5%, P<0.001). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd and 51.0% with VRd) and thrombocytopenia (29.1% and 17.3%, respectively). Serious adverse events occurred in 57.0% of the patients in the D-VRd group and 49.3% of those in the VRd group. CONCLUSIONS: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.).

PhageScope: a well-annotated bacteriophage database with automatic analyses and visualizations.

Bacteriophages are viruses that infect bacteria or archaea. Understanding the diverse and intricate genomic architectures of phages is essential to study microbial ecosystems and develop phage therapy strategies. However, the existing phage databases are short of meticulous annotations. To this end, we propose PhageScope (https://phagescope.deepomics.org), an online phage database with comprehensive annotations. PhageScope harbors a collection of 873 718 phage sequences from various sources. Applying fifteen state-of-the-art tools to perform systematic annotations and analyses, PhageScope provides annotations on genome completeness, host range, lifestyle information, taxonomy classification, nine types of structural and functional genetic elements, and three types of comparative genomic studies for curated phages. Additionally, PhageScope incorporates automatic analyses and visualizations for curated and customized phages, serving as an efficient platform for phage study.

Coding genomes with gapped pattern graph convolutional network.

MOTIVATION: Genome sequencing technologies reveal a huge amount of genomic sequences. Neural network-based methods can be prime candidates for retrieving insights from these sequences because of their applicability to large and diverse datasets. However, the highly variable lengths of genome sequences severely impair the presentation of sequences as input to the neural network. Genetic variations further complicate tasks that involve sequence comparison or alignment. RESULTS: Inspired by the theory and applications of "spaced seeds," we propose a graph representation of genome sequences called "gapped pattern graph." These graphs can be transformed through a Graph Convolutional Network to form lower-dimensional embeddings for downstream tasks. On the basis of the gapped pattern graphs, we implemented a neural network model and demonstrated its performance on diverse tasks involving microbe and mammalian genome data. Our method consistently outperformed all the other state-of-the-art methods across various metrics on all tasks, especially for the sequences with limited homology to the training data. In addition, our model was able to identify distinct gapped pattern signatures from the sequences. AVAILABILITY AND IMPLEMENTATION: The framework is available at https://github.com/deepomicslab/GCNFrame.

Heritable changes of epialleles near genes in maize can be triggered in the absence of CHH methylation.

Trans-chromosomal interactions resulting in changes in DNA methylation during hybridization have been observed in several plant species. However, little is known about the causes or consequences of these interactions. Here, we compared DNA methylomes of F1 hybrids that are mutant for a small RNA biogenesis gene, Mop1 (Mediator of paramutation1), with that of their parents, wild-type siblings, and backcrossed progeny in maize (Zea mays). Our data show that hybridization triggers global changes in both trans-chromosomal methylation (TCM) and trans-chromosomal demethylation (TCdM), most of which involved changes in CHH methylation. In more than 60% of these TCM differentially methylated regions (DMRs) in which small RNAs are available, no significant changes in the quantity of small RNAs were observed. Methylation at the CHH TCM DMRs was largely lost in the mop1 mutant, although the effects of this mutant varied depending on the location of these DMRs. Interestingly, an increase in CHH at TCM DMRs was associated with enhanced expression of a subset of highly expressed genes and suppressed expression of a small number of lowly expressed genes. Examination of the methylation levels in backcrossed plants demonstrates that both TCM and TCdM can be maintained in the subsequent generation, but that TCdM is more stable than TCM. Surprisingly, although increased CHH methylation in most TCM DMRs in F1 plants required Mop1, initiation of a new epigenetic state of these DMRs did not require a functional copy of this gene, suggesting that initiation of these changes is independent of RNA-directed DNA methylation.

Probabilistic tensor decomposition extracts better latent embeddings from single-cell multiomic data.

Single-cell sequencing technology enables the simultaneous capture of multiomic data from multiple cells. The captured data can be represented by tensors, i.e. the higher-rank matrices. However, the existing analysis tools often take the data as a collection of two-order matrices, renouncing the correspondences among the features. Consequently, we propose a probabilistic tensor decomposition framework, SCOIT, to extract embeddings from single-cell multiomic data. SCOIT incorporates various distributions, including Gaussian, Poisson, and negative binomial distributions, to deal with sparse, noisy, and heterogeneous single-cell data. Our framework can decompose a multiomic tensor into a cell embedding matrix, a gene embedding matrix, and an omic embedding matrix, allowing for various downstream analyses. We applied SCOIT to eight single-cell multiomic datasets from different sequencing protocols. With cell embeddings, SCOIT achieves superior performance for cell clustering compared to nine state-of-the-art tools under various metrics, demonstrating its ability to dissect cellular heterogeneity. With the gene embeddings, SCOIT enables cross-omics gene expression analysis and integrative gene regulatory network study. Furthermore, the embeddings allow cross-omics imputation simultaneously, outperforming current imputation methods with the Pearson correlation coefficient increased by 3.38-39.26%; moreover, SCOIT accommodates the scenario that subsets of the cells are with merely one omic profile available.

A single local delivery of paclitaxel and nucleic acids via an immunoactive polymer eliminates tumors and induces antitumor immunity.

Despite recent advances in cancer therapy, hard-to-reach, unidentified tumors remain a significant clinical challenge. A promising approach is to treat locatable and accessible tumors locally and stimulate antitumor immunity in situ to exert systemic effects against distant tumors. We hypothesize that a carrier of immunotherapeutics can play a critical role in activating antitumor immunity as an immunoadjuvant and a local retainer of drug combinations. Here, we develop a polyethyleneimine-lithocholic acid conjugate (2E'), which forms a hydrophobic core and cationic surface to codeliver hydrophobic small molecules and anionic nucleic acids and activates antigen-presenting cells via the intrinsic activities of 2E' components. 2E' delivers paclitaxel and small-interfering RNA (siRNA) targeting PD-L1 (or cyclic dinucleotide, [CDN]) to induce the immunogenic death of tumor cells and maintain the immunoactive tumor microenvironment, and further activates dendritic cells and macrophages, leveraging the activities of loaded drugs. A single local administration of 2E' or its combination with paclitaxel and PD-L1­targeting siRNA or CDN induces strong antitumor immunity, resulting in immediate regression of large established tumors, tumor-free survival, an abscopal effect on distant tumors, and resistance to rechallenge and metastasis in multiple models of murine tumors, including CT26 colon carcinoma, B16F10 melanoma, and 4T1 breast cancer. This study supports the finding that local administration of immunotherapeutics, when accompanied by the rationally designed carrier, can effectively protect the host from distant and recurrent diseases.

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial.

BACKGROUND: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA. METHODS: CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18-65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383. FINDINGS: Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7-85·6) from first randomisation and 70·6 months (66·4-76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9-not estimable (NE)] vs 45·8 months [41·8-49·6]; HR 0·49 [95% CI 0·40-0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6-NE] vs 72·1 months [52·8-NE]; 0·76 [0·58-1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9-NE] vs 32·7 months [27·2-38·7]; 0·34 [0·26-0·44]; p<0·0001). INTERPRETATION: The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma. FUNDING: Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development.

Increased Siglec-9/Siglec-9L interactions on NK cells predict poor HCC prognosis and present a targetable checkpoint for immunotherapy.

BACKGROUND & AIMS: Natural killer (NK) cell-based anti-hepatocellular carcinoma (HCC) therapy is an increasingly attractive approach that warrants further study. Siglec-9 interacts with its ligand (Siglec-9L) and restrains NK cell functions, suggesting it is a potential therapeutic target. However, in situ Siglec-9/Siglec-9L interactions in HCC have not been reported, and a relevant interventional strategy is lacking. Herein, we aim to illustrate Siglec-9/Siglec-9L-mediated cell sociology and identify small-molecule inhibitors targeting Siglec-9 that could improve the efficacy of NK cell-based immunotherapy for HCC. METHODS: Multiplexed immunofluorescence staining was performed to analyze the expression pattern of Siglec-7, -9 and their ligands in HCC tissues. Then we conducted docking-based virtual screening combined with bio-layer interferometry assays to identify a potent small-molecule Siglec-9 inhibitor. The therapeutic potential was further evaluated in vitro and in hepatoma-bearing NCG mice. RESULTS: Siglec-9 expression, rather than Siglec-7, was markedly upregulated on tumor-infiltrating NK cells, which correlated significantly with reduced survival of patients with HCC. Moreover, the number of Siglec-9L+ cells neighboring Siglec-9+ NK cells was increased in HCC tissues and was also associated with tumor recurrence and reduced survival, further suggesting that Siglec-9/Siglec-9L interactions are a potential therapeutic target in HCC. In addition, we identified a small-molecule Siglec-9 inhibitor MTX-3937 which inhibited phosphorylation of Siglec-9 and downstream SHP1 and SHP2. Accordingly, MTX-3937 led to considerable improvement in NK cell function. Notably, MTX-3937 enhanced cytotoxicity of both human peripheral and tumor-infiltrating NK cells. Furthermore, transfer of MTX-3937-treated NK92 cells greatly suppressed the growth of hepatoma xenografts in NCG mice. CONCLUSIONS: Our study provides the rationale for HCC treatment by targeting Siglec-9 on NK cells and identifies a promising small-molecule inhibitor against Siglec-9 that enhances NK cell-mediated HCC surveillance. IMPACT AND IMPLICATIONS: Herein, we found that Siglec-9 expression is markedly upregulated on tumor-infiltrating natural killer (TINK) cells and correlates with reduced survival in patients with hepatocellular carcinoma (HCC). Moreover, the number of Siglec-9L+ cells neighboring Siglec-9+ NK cells was increased in HCC tissues and was also associated with tumor recurrence and reduced survival. More importantly, we identified a small-molecule inhibitor targeting Siglec-9 that augments NK cell functions, revealing a novel immunotherapy strategy for liver cancer that warrants further clinical investigation.

Magnetic Nanoparticles: A Review on Synthesis, Characterization, Functionalization, and Biomedical Applications.

Nowadays, magnetic nanoparticles (MNPs) are applied in numerous fields, especially in biomedical applications. Since biofluidic samples and biological tissues are nonmagnetic, negligible background signals can interfere with the magnetic signals from MNPs in magnetic biosensing and imaging applications. In addition, the MNPs can be remotely controlled by magnetic fields, which make it possible for magnetic separation and targeted drug delivery. Furthermore, due to the unique dynamic magnetizations of MNPs when subjected to alternating magnetic fields, MNPs are also proposed as a key tool in cancer treatment, an example is magnetic hyperthermia therapy. Due to their distinct surface chemistry, good biocompatibility, and inducible magnetic moments, the material and morphological structure design of MNPs has attracted enormous interest from a variety of scientific domains. Herein, a thorough review of the chemical synthesis strategies of MNPs, the methodologies to modify the MNPs surface for better biocompatibility, the physicochemical characterization techniques for MNPs, as well as some representative applications of MNPs in disease diagnosis and treatment are provided. Further portions of the review go into the diagnostic and therapeutic uses of composite MNPs with core/shell structures as well as a deeper analysis of MNP properties to learn about potential biomedical applications.

Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE.

In patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab reduced the risk of disease progression or death by 44% in MAIA (daratumumab/lenalidomide/dexamethasone [D-Rd]) and 58% in ALCYONE (daratumumab/bortezomib/melphalan/prednisone [D-VMP]). Minimal residual disease (MRD) is a sensitive measure of disease and response to therapy. MRD-negativity status and durability were assessed in MAIA and ALCYONE. MRD assessments using next-generation sequencing (10-5) occurred for patients achieving complete response (CR) or better and after at least CR at 12, 18, 24, and 30 months from the first dose. Progression-free survival (PFS) by MRD status and sustained MRD negativity lasting ≥6 and ≥12 months were analyzed in the intent-to-treat population and among patients achieving at least CR. In MAIA (D-Rd, n = 368; lenalidomide and dexamethasone [Rd], n = 369) and ALCYONE (D-VMP, n = 350; bortezomib/melphalan/prednisone [VMP], n = 356), the median duration of follow-up was 36.4 and 40.1 months, respectively. MRD-negative status and sustained MRD negativity lasting ≥6 and ≥12 months were associated with improved PFS, regardless of treatment group. However, daratumumab-based therapy improved rates of MRD negativity lasting ≥6 months (D-Rd, 14.9% vs Rd, 4.3%; D-VMP, 15.7% vs VMP, 4.5%) and ≥12 months (D-Rd, 10.9% vs Rd, 2.4%; D-VMP, 14.0% vs VMP, 2.8%), both of which translated to improved PFS vs control groups. In a pooled analysis, patients who were MRD negative had improved PFS vs patients who were MRD positive. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes. These trials were registered at www.clinicaltrials.gov as #NCT02252172 (MAIA) and #NCT02195479 (ALCYONE).

Prognostic value of minimal residual disease negativity in myeloma: combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA.

We explored minimal residual disease (MRD) in relapsed/refractory multiple myeloma (RRMM) and transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) using data from 4 phase 3 studies (POLLUX, CASTOR, ALCYONE, and MAIA). Each study previously demonstrated that daratumumab-based therapies improved MRD negativity rates and reduced the risk of disease progression or death by approximately half vs standards of care. We conducted a large-scale pooled analysis for associations between patients achieving complete response or better (≥CR) with MRD-negative status and progression-free survival (PFS). MRD was assessed via next-generation sequencing (10-5 sensitivity threshold). Patient-level data were pooled from all 4 studies and for patients with TIE NDMM and patients with RRMM who received ≤2 prior lines of therapy (≤2 PL). PFS was evaluated by response and MRD status. Median follow-up (months) was 54.8 for POLLUX, 50.2 for CASTOR, 40.1 for ALCYONE, and 36.4 for MAIA. Patients who achieved ≥CR and MRD negativity had improved PFS vs those who failed to reach CR or were MRD positive (TIE NDMM and RRMM hazard ratio [HR] 0.20, P < .0001; TIE NDMM and RRMM ≤2 PL HR 0.20, P < .0001). This benefit occurred irrespective of therapy or disease setting. A time-varying Cox proportional hazard model confirmed that ≥CR with MRD negativity was associated with improved PFS. Daratumumab-based treatment was associated with more patients reaching ≥CR and MRD negativity. These findings represent the first large-scale analysis with robust methodology to support ≥CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM. These trials were registered at www.clinicaltrials.gov as #NCT02076009, #NCT02136134, #NCT02195479, and #NCT02252172.

Optical authentication scheme based on all-optical neural network.

Diffractive deep neural network is architectural designs based on the principles of neural networks, which consists of multiple diffraction layers and has the remarkable ability to perform machine learning tasks at the speed of light. In this paper, a novel optical authentication system was presented that utilizes the diffractive deep neural network principle. By carefully manipulating a light beam with both a public key and a private key, we are able to generate a unique and secure image representation at a precise distance. The generated image can undergo authentication by being processed through the proposed authentication system. Leveraging the utilization of invisible terahertz light, the certification system possesses inherent characteristics of concealment and enhanced security. Additionally, the entire certification process operates solely through the manipulation of the light beam, eliminating the need for electronic calculations. As a result, the system offers rapid certification speed. The proposed optical authentication scheme is further validated through computer simulations, which showcase its robust security and high precision. This method holds immense potential for diverse applications in optical neural network authentication, warranting a broad scope of future prospects.

Experimental study of laser spot tracking for underwater optical wireless communication.

In this paper, a novel laser spot tracking algorithm that incorporates the Kalman filter with the continuously adaptive Meanshift algorithm (Cam-Kalm) is proposed and employed in an underwater optical wireless communication (UOWC) system. Since the Kalman filter has the advantage of predicting the state information of the target spot based on its spatial motion features, the proposed algorithm can improve the accuracy and stability of the moving laser spot tracking. A 2 m optical wireless communication experimental system with auto-tracking based on a green laser diode (LD) is built to evaluate the tracking performance of different algorithms. Experimental results verify that the proposed algorithm outperforms conventional tracking algorithms in aspects of tracking accuracy, interference resistance, and response time. With the proposed Cam-Kalm algorithm, the experimental system can establish an effective communication link, while the maximum tracking speed is 20 mm/s given the forward-error-correction (FEC) threshold.

Long-term Changes in Low Anterior Resection Syndrome in Survivors of Rectal Cancer: Longitudinal Follow-up of a Randomized Controlled Trial.

BACKGROUND: Postoperative bowel dysfunction, also known as low anterior resection syndrome, is common in rectal cancer survivors and significantly impacts quality of life. Although long-term longitudinal follow-up is lacking, improvement of the syndrome is commonly believed to happen only within the first 2 years. OBJECTIVE: This study aimed to depict the longitudinal evolvement of low anterior resection syndrome beyond 3 years and explore factors associated with changes. DESIGN: Longitudinal long-term follow-ups were performed for the single center with the largest cohort within the multicenter FOWARC randomized controlled trial. SETTING: A quaternary referral center. PATIENTS: Individuals diagnosed with rectal cancer who received long-course neoadjuvant chemotherapy or chemoradiotherapy, followed by sphincter-preserving radical proctectomy. MAIN OUTCOME MEASUREMENTS: Change of low anterior resection syndrome score and stoma status. RESULTS: Of the 220 patients responding to the first follow-up at a median of 39 months, 178 (80.9%) responded to the second follow-up after a median of 83 months. During this interval, the mean low anterior resection syndrome score improved from 29.5 (95% CI, 28.3-30.7) to 18.6 (95% CI, 16.6-20.6). Fifty-six (31.5%) patients reported improvement from major to no/minor severity, and 6 (3.4%) patients had new stomas because of severe bowel dysfunction. Neoadjuvant radiotherapy ( p = 0.016) was independently and negatively associated with improvement of the score. LIMITATIONS: Loss of follow-up during the long-term follow-ups. CONCLUSIONS: Most rectal cancer survivors with low anterior resection syndrome continued to improve beyond 3 years after proctectomy. Neoadjuvant radiotherapy was negatively associated with long-term improvement of low anterior resection syndrome. See Video Abstract . CAMBIO A LARGO PLAZO DEL SNDROME DE RESECCIN ANTERIOR BAJA EN SUPERVIVIENTES DE CNCER DE RECTO SEGUIMIENTO LONGITUDINAL DE UN ENSAYO CONTROLADO ALEATORIO: ANTECEDENTES:La disfunción intestinal posoperatoria, también conocida como síndrome de resección anterior baja, es común en los sobrevivientes de cáncer de recto y afecta significativamente la calidad de vida. Aunque falta un seguimiento longitudinal a largo plazo, comúnmente se cree que la mejoría del síndrome ocurre sólo dentro de los primeros dos años.OBJETIVO:Este estudio tiene como objetivo representar la evolución longitudinal del síndrome de resección anterior baja más allá de los 3 años y explora los factores asociados con el cambio.DISEÑO:Se realizaron seguimientos longitudinales a largo plazo para el único centro con la cohorte más grande dentro del ensayo controlado aleatorio multicéntrico FOWARC.AJUSTE:Un centro de referencia cuaternario.PACIENTES:Individuos diagnosticados con cáncer de recto que recibieron quimioterapia neoadyuvante de larga duración o quimiorradioterapia, seguida de proctectomía radical con preservación del esfínter.PRINCIPALES MEDICIONES DE RESULTADO:Cambio en la puntuación del síndrome de resección anterior baja y el estado del estoma.RESULTADOS:De los 220 pacientes que respondieron al primer seguimiento con una mediana de 39 meses, 178 (80,9%) respondieron al segundo seguimiento después de una mediana de 83 meses. Durante el intervalo, la puntuación media del síndrome de resección anterior baja mejoró de 29,5 (intervalo de confianza [IC] del 95%: 28,3-30,7) a 18,6 (IC del 95%: 16,6-20,6). 56 (31,5%) pacientes informaron una mejoría de mayor a ninguna gravedad, y 6 (3,4%) pacientes tuvieron un nuevo estoma debido a una disfunción intestinal grave. La radiación neoadyuvante (p = 0,016) se asoció de forma independiente y negativa con la mejora de la puntuación.LIMITACIONES:Pérdida de seguimiento durante los seguimientos a largo plazo.CONCLUSIÓN:La mayoría de los sobrevivientes de cáncer de recto con síndrome de resección anterior baja continuaron mejorando más allá de los 3 años después de la proctectomía. La radiación neoadyuvante se asoció negativamente con la mejora a largo plazo del síndrome de resección anterior baja. (Traducción-Dr Yolanda Colorado ).

Dipeniroqueforins A-B and Peniroqueforin D: Eremophilane-Type Sesquiterpenoid Derivatives with Cytotoxic Activity from Penicillium roqueforti.

Guided by the Global Natural Products Social (GNPS) molecular networking strategy, five undescribed eremophilane-type sesquiterpenoid derivatives (1-5) were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of plant Hypericum beanii collected in Shennongjia Forestry District, Hubei Province. Dipeniroqueforins A-B (1-2), representing a lactam-type sesquiterpenoid skeleton with a highly symmetrical and homodimeric 5/6/6-6/6/5 hexacyclic system, are reported within the eremophilane-type family for the first time. Peniroqueforin D (5) represents the first example of a 1,2-seco eremophilane-type sesquiterpenoid derivative featuring an undescribed 7/6-fused ring system. The structures of these compounds were elucidated by various spectroscopic analyses, DP4+ probability analyses, ECD calculations, and single-crystal X-ray diffraction experiments. Furthermore, these isolates were evaluated for cytotoxicity, and the result uncovered that compound 1 displayed broad-spectrum activity. Further mechanistic study revealed that compound 1 could significantly upregulate the mRNA expression of genes related to the oxidative induction, leading to the abnormal ROS levels in tumor cells and ultimately causing tumor cell apoptosis.

Cryptic piperazine derivatives activated by knocking out the global regulator LaeA in Aspergillus flavipes.

Genome sequencing on an intertidal zone-derived Aspergillus flavipes strain revealed its great potential to produce secondary metabolites. To activate the cryptic compounds of A. flavipes, the global regulator flLaeA was knocked out, leading to substantial up-regulation of the expression of two NRPS-like biosynthetic gene clusters in the ΔflLaeA mutant. With a scaled-up fermentation of the ΔflLaeA strain, five compounds, including two previously undescribed piperazine derivatives flavipamides A and B (1 and 2), along with three known compounds (3-5), were obtained by LC-MS guided isolation. The new compounds were elucidated by spectroscopic analysis and electronic circular dichroism (ECD) calculations, and the biosynthetic pathway was proposed on the bias of bioinformatic analysis and 13C isotope labeling evidence. This is the first report to access cryptic fungi secondary metabolites by inactivating global regulator LaeA and may provide a new approach to discovering new secondary metabolites by such genetic manipulation.