Polymerization-Induced Hierarchical Hybrid Particles from Siloxane Emulsification Endowing Polyurethane Composite Coating with Superhydrophobicity, Thermal Insulation, and Fluorescence.

Hierarchically structural particles (HSPs) are highly regarded as favorable nanomaterials for superhydrophobic coating due to their special multiscale structure and surface physicochemical properties. However, most of the superhydrophobic coatings constructed from HSPs are monofunctional, constraining their broader applications. Moreover, traditional methods for constructing HSPs mostly rely on complicated chemical routes and template removal. Herein, we propose an innovative strategy (one-pot method) for producing multifunctional hierarchical hybrid particles (HHPs). Polysilsesquioxane (PSQ), generated from hydrolysis condensation of methyltriethoxylsilane, is used as the sole stabilizer to anchor on the surface of styrene and short fluoroalkyl compound tridecafluorooctyl acrylate comonomers droplets, forming a mesoporous PSQ shell. Subsequently, the comonomers inside of the shell perform restricted polymerization to generate the HHP due to the driving of the mesoporous capillary force. The HHP is then mixed with waterborne polyurethane (WPU) to develop a robust nanocomposite coating (WPU-HHP). Through the deliberate design of the HHP components, the WPU-HHP coating has thermal insulation, photoluminescence properties, and the ability to achieve a wettability transition during abrasion. Our research has achieved the integration of multifunctionality in one waterborne hybrid system, broadening the application areas of nanocomposite coatings.

Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

BACKGROUND: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer. METHODS: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China. Patients aged 18-75 years with untreated mismatch repair-deficient or microsatellite instability-high or POLE/POLD1-mutated locally advanced colorectal cancer (cT3 or N+ for rectal cancer, and T3 with invasion ≥5mm or T4, with or without N+ for colon cancer) and an Eastern Cooperative Oncology Group performance score of 0-1 were enrolled and given 200 mg camrelizumab intravenously on day 1 and 250 mg apatinib orally from day 1-14, every 3 weeks for 3 months followed by surgery or 6 months if patients did not have surgery. Patients who had a clinical complete response did not undergo surgery and proceeded with a watch-and-wait approach. The primary endpoint was the proportion of patients with a pathological or clinical complete response. Eligible enrolled patients who received at least one cycle of neoadjuvant treatment and had at least one tumour response assessment following the baseline assessment were included in the activity analysis, and patients who received at least one dose of study drug were included in the safety analysis. The study is registered with ClinicalTrials.gov (NCT04715633) and is ongoing. FINDINGS: Between Sept 29, 2020, and Dec 15, 2022, 53 patients were enrolled; one patient was excluded from the activity analysis because they were found to be mismatch repair-proficient and microsatellite-stable. 23 (44%) patients were female and 29 (56%) were male. The median follow-up was 16·4 (IQR 10·5-23·5) months. 28 (54%; 95% CI 35-68) patients had a clinical complete response and 24 of these patients were managed with a watch-and-wait approach, including 20 patients with colon cancer and multiple primary colorectal cancer. 23 (44%) of 52 patients underwent surgery for the primary tumour, and 14 (61%; 95% CI 39-80) had a pathological complete response. 38 (73%; 95% CI 59-84) of 52 patients had a complete response. Grade 3-5 adverse events occurred in 20 (38%) of 53 patients; the most common were increased aminotransferase (six [11%]), bowel obstruction (four [8%]), and hypertension (four [8%]). Drug-related serious adverse events occurred in six (11%) of 53 patients. One patient died from treatment-related immune-related hepatitis. INTERPRETATION: Neoadjuvant camrelizumab plus apatinib show promising antitumour activity in patients with locally advanced mismatch repair-deficient or microsatellite instability-high colorectal cancer. Immune-related adverse events should be monitored with the utmost vigilance. Organ preservation seems promising not only in patients with rectal cancer, but also in those with colon cancer who have a clinical complete response. Longer follow-up is needed to assess the oncological outcomes of the watch-and-wait approach. FUNDING: The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, and the Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Novel strategies for modulating the gut microbiome for cancer therapy.

Recent advancements in genomics, transcriptomics, and metabolomics have significantly advanced our understanding of the human gut microbiome and its impact on the efficacy and toxicity of anti-cancer therapeutics, including chemotherapy, immunotherapy, and radiotherapy. In particular, prebiotics, probiotics, and postbiotics are recognized for their unique properties in modulating the gut microbiota, maintaining the intestinal barrier, and regulating immune cells, thus emerging as new cancer treatment modalities. However, clinical translation of microbiome-based therapy is still in its early stages, facing challenges to overcome physicochemical and biological barriers of the gastrointestinal tract, enhance target-specific delivery, and improve drug bioavailability. This review aims to highlight the impact of prebiotics, probiotics, and postbiotics on the gut microbiome and their efficacy as cancer treatment modalities. Additionally, we summarize recent innovative engineering strategies designed to overcome challenges associated with oral administration of anti-cancer treatments. Moreover, we will explore the potential benefits of engineered gut microbiome-modulating approaches in ameliorating the side effects of immunotherapy and chemotherapy.

Rigid Phase Formation and Sb3+ Doping of Tin (IV) Halide Hybrids toward Photoluminescence Enhancement and Tuning for Anti-Counterfeiting and Information Encryption.

Multi-excitonic emitting materials in luminescent metal halides are emerging candidates for anti-counterfeiting and information encryption applications. Herein, ATPP2SnCl6 (ATPP = acetonyltriphenylphosphonium) phase was designed and synthesized by rationally choosing emissive organic reagent of ATPPCl and non-toxic stable metal ions of Sn4+, and Sb3+ was further doped into ATPP2SnCl6 to tune the photoluminescence with external self-trapped excitons emission. The derived non-toxic ATPP2SnCl6 shows multi-excitonic luminescent centers verified by optical study and differential charge-density from density functional theory calculations. Incorporation of Sb3+ dopants and the increasing concentrations induce the efficient energy transfer therein, thus enhancing photoluminescence quantum yield from 5.1% to 73.8%. The multi-excitonic emission inspires the creation of information encryption and decryption by leveraging the photoluminescence from ATPPCl to ATPP2SnCl6 host and ATPP2SnCl6:Sb3+. This study facilitates the anti-counterfeiting application by employing solution-processable luminescent metal halides materials with excitation-dependent PL properties.

Glymphatic abnormality in systemic lupus erythematosus detected by diffusion tensor image analysis along the perivascular space.

OBJECTIVES: This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain. METHODS: In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted. RESULTS: SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss. CONCLUSION: The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients.

Involvement of Chemosensory Protein CrufCSP3 in Perception of the Host Location in a Parasitic Wasp Cotesia ruficrus.

Chemosensory proteins (CSPs) constitute a class of olfactory proteins localized in insect sensory organs that serve a crucial function in decoding external chemical stimuli. This study aims to elucidate the involvement of CrufCSP3 in olfactory perception within the context of Cotesia ruficrus, an indigenous endoparasitoid targeting the invasive pest Spodoptera frugiperda. Through fluorescence-competitive binding assays and site-directed mutagenesis, we pinpointed four amino acids as pivotal residues involved in the interaction between CrufCSP3 and five host-related compounds. Subsequent RNA interference experiments targeting CrufCSP3 unveiled a reduced sensitivity to specific host-related compounds and a decline in the parasitism rate of the FAW larvae. These findings unequivocally indicate the essential role of CrufCSP3 in the chemoreception process of C. ruficrus. Consequently, our study not only sheds light on the functional importance of CSPs in parasitic wasp behavior but also contributes to the development of eco-friendly and efficacious wasp behavior modifiers for effectively mitigating pest population surges.

Flexible Janus Black Silicon Photothermal Conversion Membranes for Highly Efficient Solar-Driven Interfacial Water Purification.

Photothermal conversion materials are critical in the development of solar-driven interfacial evaporation techniques; however, achieving a high energy conversion efficiency remains challenging owing to the high cost and instability of light-absorbing materials, in addition to the difficulties of simultaneously improving light absorption while suppressing heat loss. A black silicon (Si) powder with a porous structure was prepared by chemical etching of a low-cost commercial micron-sized Al-Si alloy, and a flexible Janus black Si photothermal conversion membrane was constructed. The partially broken spherical particles and porous structure obtained after etching enhanced the refraction of light from the Si powder, imparting the prepared membrane with an average light absorption rate of 95.95% over the solar spectrum. Evaporation from the membrane increased the intermediate water content and reduced the equivalent evaporation enthalpy. The thermal conduction loss was inhibited through a one-dimensional water transport structure, and the membrane achieved a water evaporation rate of 2.17 kg m-2 h-1 and a photothermal efficiency of 94.95% under 1 sun illumination. Benefiting from the broadband absorption and high photothermal efficiency of black Si powder, surface modification of hydrophobic polydimethylsiloxane, and directional salt-out structure design, the evaporation rate of the Janus black Si membrane-based system in a 10% NaCl solution was maintained >2.10 kg m-2 h-1 after 7 days of continuous evaporation cycles. The removal rate of metal ions from simulated seawater and from practical wastewater containing complex heavy metals reached >99.9%, indicating the promising potential of black Si membrane for application in solar-driven interfacial water purification.

Theoretical Study of the Ternary Compound Monolayer CuP2Se for Photocatalytic Water Splitting with Efficient Optical Absorption.

Utilizing photocatalytic method to produce hydrogen by splitting water is an efficient strategy to solve the hotspot issues of energy crisis and environmental pollution. Herein, we systematically investigate the corresponding properties of the reported Cu-bearing ternary compound monolayer CuP2Se by using the first-principle calculations. The monolayer CuP2Se has quite small cleavage energy of 0.51 J/m2, indicating it can be easily produced by the mechanical exfoliation method experimentally. In addition, it is an indirect bandgap semiconductor material which has a moderate value of 1.91 eV. The conduction band minimum (CBM) and valence band maximum (VBM) can perfectly straddle the redox potentials of water when a biaxial strain of -4% to 4% is applied, unveiling the high photocatalytic thermodynamic stability of monolayer CuP2Se in response to the effect of solvent tension. Remarkably, the monolayer CuP2Se also demonstrates significant sunlight capturing ability in the visible region. The outstanding electronic and optical properties suggest that the monolayer CuP2Se is undoubtedly a viable material for photocatalytic water splitting.

A New Dy(III) Complex: Fluorescence Performances, Loading with Resveratrol-Hydrogels Against Skin Aging and Molecular Docking.

In the present research, novel lanthanide coordination compounds [DyL(PhCOO)(CH3OH)](ClO4)2·(CH3OH)2 (1) were characterized by the compression of 2,6-diformyl-4-methyl-phenol (dmp) and 1,3-diamino-2-propanol using benzoate as the secondary ligand, where L indicates the deprotonated macrocyclic ligand. Through the high structural rigidity driven by the coordination of the macrocyclic ligand formed by condensation in methanol solution and sodium benzoate with Dy(ClO4)3·6H2O, compound 1 exhibits outstanding cyan-emitting fluorescence performance and potential applications as a fluorescent material. Additionally, hyaluronic acid (HA)/ carboxymethyl chitosan (CMCS) hydrogels were prepared with loaded resveratrol metal-organic complexes according to the synthetic chemical approach. In biological study, we evaluated the effect of hydrogels on oxidative stress on human dermal fibroblasts. Examined by molecular docking simulation, the results showed that the binding interactions were from the phenol group, the carboxyl group and also the "-N=" group, indicating Dy metal complex has excellent biological capability.

Non-cytotoxic nanomolar concentration of arctigenin protects neuronal cells from chemotherapy-induced ferroptosis by regulating SLC7A11-cystine-cysteine axis.

Neurotoxicity is a common side effect of certain types of therapeutic drugs, posing a major hurdle for their clinical application. Accumulating evidence suggests that ferroptosis is involved in the neurotoxicity induced by these drugs. Therefore, targeting ferroptosis is considered to be a reasonable approach to prevent such side effect. Arctigenin (ATG) is a major bioactive ingredient of Arctium lappa L., a popular medicinal plant in Asia, and has been reported to have multiple bioactivities including neuroprotection. However, the mechanisms underlying the neuroprotection of ATG has not been well elucidated. The purpose of this study was to investigate whether the neuroprotection of ATG was associated with its ability to protect neuronal cells from ferroptosis. Using neuronal cell ferroptosis model induced by either classic ferroptosis induces or therapeutic drugs, we demonstrated for the first time that ATG in the nanomolar concentration range effectively prevented neuronal cell ferroptosis induced by classic ferroptosis inducer sulfasalazine (SAS) and erastin (Era), or therapeutic drug oxaliplatin (OXA) and 5-fluorouracil (5-FU). Mechanistically, we uncovered that the anti-ferroptotic effect of ATG was attributed to its ability to activate SLC7A11-cystine-cysteine axis. The findings of the present study implicate that ATG holds great potential to be developed as a novel agent for preventing SLC7A11 inhibition-mediated neurotoxicity.

Efficient single-pixel imaging based on a compact fiber laser array and untrained neural network.

This paper presents an efficient scheme for single-pixel imaging (SPI) utilizing a phase-controlled fiber laser array and an untrained deep neural network. The fiber lasers are arranged in a compact hexagonal structure and coherently combined to generate illuminating light fields. Through the utilization of high-speed electro-optic modulators in each individual fiber laser module, the randomly modulated fiber laser array enables rapid speckle projection onto the object of interest. Furthermore, the untrained deep neural network is incorporated into the image reconstructing process to enhance the quality of the reconstructed images. Through simulations and experiments, we validate the feasibility of the proposed method and successfully achieve high-quality SPI utilizing the coherent fiber laser array at a sampling ratio of 1.6%. Given its potential for high emitting power and rapid modulation, the SPI scheme based on the fiber laser array holds promise for broad applications in remote sensing and other applicable fields.

Self-Powered Agricultural Product Preservation and Wireless Monitoring Based on Dual-Functional Triboelectric Nanogenerator.

The global annual vegetable and fruit waste accounts for more than one-fifth of food waste, mainly due to deterioration. In addition, agricultural product spoilage can produce foodborne illnesses and threaten public health. Eco-friendly preservation technologies for extending the shelf life of agricultural products are of great significance to socio-economic development. Here, we report a dual-functional TENG (DF-TENG) that can simultaneously prolong the storage period of vegetables and realize wireless storage condition monitoring by harvesting the rotational energy. Under the illumination of the self-powered high-voltage electric field, the deterioration of vegetables can be effectively slowed down. It can not only decrease the respiration rate and weight loss of pakchoi but also increase the chlorophyll levels (∼33.1%) and superoxide dismutase activity (∼11.1%) after preservation for 4 days. Meanwhile, by harvesting the rotational energy, the DF-TENG can be used to drive wireless sensors for monitoring the storage conditions and location information of vegetables during transportation in real time. This work provides a new direction for self-powered systems in cost-effective and eco-friendly agricultural product preservation, which may have far-reaching significance to the construction of a sustainable society for reducing food waste.

Consistent signatures in the human gut microbiome of old- and young-onset colorectal cancer.

The incidence of young-onset colorectal cancer (yCRC) has been increasing in recent decades, but little is known about the gut microbiome of these patients. Most studies have focused on old-onset CRC (oCRC), and it remains unclear whether CRC signatures derived from old patients are valid in young patients. To address this, we assembled the largest yCRC gut metagenomes to date from two independent cohorts and found that the CRC microbiome had limited association with age across adulthood. Differential analysis revealed that well-known CRC-associated taxa, such as Clostridium symbiosum, Peptostreptococcus stomatis, Parvimonas micra and Hungatella hathewayi were significantly enriched (false discovery rate <0.05) in both old- and young-onset patients. Similar strain-level patterns of Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were observed for oCRC and yCRC. Almost all oCRC-associated metagenomic pathways had directionally concordant changes in young patients. Importantly, CRC-associated virulence factors (fadA, bft) were enriched in both oCRC and yCRC compared to their respective controls. Moreover, the microbiome-based classification model had similar predication accuracy for CRC status in old- and young-onset patients, underscoring the consistency of microbial signatures across different age groups.

Glycyrol Alleviates Acute Kidney Injury by Inhibiting Ferroptsis.

Acute kidney injury (AKI) is a common clinical problem with high morbidity and mortality. The discovery of ferroptosis has provided novel insights into the mechanisms underlying AKI and paves the way for developing ferroptosis-based approaches to treat AKI. Glycyrol (GC) is a representative coumarin compound isolated from licorice that demonstrates various pharmacological activities. However, its potential for a protective effect against kidney injury remains unknown. We hypothesized that GC might be able to protect against AKI via suppression of ferroptosis. This hypothesis was tested in a cell-culture model of RSL3-induced nephrocyte ferroptosis and a mouse model of folic acid-induced AKI. The results showed that GC exerted a significant protective effect against nephrocyte ferroptosis in vitro and was effective against folic acid-induced AKI in vivo, where it was mechanistically associated with suppressing HO-1-mediated heme degradation. Collectively, the findings of the present study support the hypothesis that GC holds considerable potential to be developed as a novel agent for treating ferroptosis-related AKI.

Effects of train vibration load on the structure and hydraulic properties of soils.

Investigating the impact of train-induced vibration loads on soil hydraulic properties, this study conducted experiments using a self-designed indoor soil seepage platform that incorporates vibration loads. The experiments were complemented with scanning electron microscopy to analyze the influence of train-induced vibration loads on soil hydraulic conductivity and its evolutionary characteristics under different vibration frequencies. The experimental results indicated that as the vibration frequency increases from no vibration (0 Hz) to 20 Hz, the time required for the soil volumetric moisture content to reach its peak and stabilize decreases rapidly. However, after the vibration frequency exceeds 20 Hz, the rate at which the time required for the volumetric moisture content to reach its peak and stabilize decreases slows down. Furthermore, the soil pore water pressure increases with the increase in vibration frequency. At a vibration frequency of 80 Hz, the peak value of pore water pressure increases by 105% compared to the non-vibration state, suggesting that higher vibration frequencies promote the development and acceleration of soil pore moisture migration. Additionally, as the vibration frequency increases, the soil hydraulic conductivity initially experiences a rapid increase, with a growth rate ranging from 40.1 to 47.4%. However, after the frequency exceeds 20 Hz, this growth rate significantly decreases, settling to only 18.6% to 7.8%. When the soil was subjected to a vibration load, the scanning electron microscopy test revealed alterations in its pore structure. Micropores and small pores transformed into macropores and mesopores. Additionally, the microstructural parameters indicated that vibration load decreased the complexity of soil pores, thereby speeding up the hydraulic conduction process. This, in turn, affected the hydraulic properties of the soil and established a relationship between pore structure complexity and soil hydraulic properties.

Systemic lupus erythematosus-related brain abnormalities in the default mode network and the limbic system: A resting-state fMRI meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an immune-mediated and multi-systemic disease which may affect the nervous system, causing neuropsychiatric SLE (NPSLE). Recent neuroimaging studies have examined brain functional alterations in SLE. However, discrepant findings were reported. This meta-analysis aims to identify consistent resting-state functional abnormalities in SLE. METHODS: PubMed and Web of Science were searched to identify candidate resting-state functional MRI studies assessing SLE. A voxel-based meta-analysis was performed using the anisotropic effect-size version of the seed-based d mapping (AES-SDM). The abnormal intrinsic functional patterns extracted from SDM were mapped onto the brain functional network atlas to determine brain abnormalities at a network level. RESULTS: Twelve studies evaluating fifteen datasets were included in this meta-analysis, comprising 572 SLE patients and 436 healthy controls (HCs). Compared with HCs, SLE patients showed increased brain activity in the bilateral hippocampus and right superior temporal gyrus, and decreased brain activity in the left superior frontal gyrus, left middle temporal gyrus, bilateral thalamus, left inferior frontal gyrus and right cerebellum. Mapping the abnormal patterns to the network atlas revealed the default mode network and the limbic system as core neural systems commonly affected in SLE. LIMITATIONS: The number of included studies is relatively small, with heterogeneous analytic methods and a risk of publication bias. CONCLUSIONS: Brain functional alterations in SLE are predominantly found in the default mode network and the limbic system. These findings uncovered a consistent pattern of resting-state functional network abnormalities in SLE which may serve as a potential objective neuroimaging biomarker.

F-free etching and ingenious construction of hydrogel layer-prepared MXene membranes for oily wastewater separation.

A strategy for the preparation of hydrogel layer MXene membranes by an F-free method was proposed. It maintained high permeance (2686.1 L m-2 h-1 bar-1) and separation efficiency (99.99%) even after 300 min of emulsion separation. The membrane resisted harsh chemical and microbiological environments and efficiently treated actual oily wastewater.

Spatially resolved single-cell atlas of ascidian endostyle provides insight into the origin of vertebrate pharyngeal organs.

The pharyngeal endoderm, an innovation of deuterostome ancestors, contributes to pharyngeal development by influencing the patterning and differentiation of pharyngeal structures in vertebrates; however, the evolutionary origin of the pharyngeal organs in vertebrates is largely unknown. The endostyle, a distinct pharyngeal organ exclusively present in basal chordates, represents a good model for understanding pharyngeal organ origins. Using Stereo-seq and single-cell RNA sequencing, we constructed aspatially resolved single-cell atlas for the endostyle of the ascidian Styela clava. We determined the cell composition of the hemolymphoid region, which illuminates a mixed ancestral structure for the blood and lymphoid system. In addition, we discovered a cluster of hair cell-like cells in zone 3, which has transcriptomic similarity with the hair cells of the vertebrate acoustico-lateralis system. These findings reshape our understanding of the pharynx of the basal chordate and provide insights into the evolutionary origin of multiplexed pharyngeal organs.

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

BACKGROUND: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy. METHODS: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method. RESULTS: A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%. CONCLUSIONS: Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.

Detecting horizontal gene transfer with metagenomics co-barcoding sequencing.

Horizontal gene transfer (HGT) is the process through which genetic information is transferred between different genomes and that played a crucial role in bacterial evolution. HGT can enable bacteria to rapidly acquire antibiotic resistance and bacteria that have acquired resistance is spreading within the microbiome. Conventional methods of characterizing HGT patterns include short-read metagenomic sequencing (short-reads mNGS), long-read sequencing, and single-cell sequencing. These approaches present several limitations, such as short-read fragments, high amounts of input DNA, and sequencing costs, respectively. Here, we attempt to circumvent present limitations to detect HGT by developing a metagenomics co-barcode sequencing workflow (MECOS) and applying it to the human and mouse gut microbiomes. In addition to that, we have over 10-fold increased contig length compared to short-reads mNGS; we also obtained exceeding 30 million paired reads with co-barcode information. Applying the novel bioinformatic pipeline, we integrated this co-barcoding information and the context information from long reads, and observed over 50-fold HGT events after we corrected the potential wrong HGT events. Specifically, we detected approximately 3,000 HGT blocks in individual samples, encompassing ~6,000 genes and ~100 taxonomic groups, including loci conferring tetracycline resistance through ribosomal protection. MECOS provides a valuable tool for investigating HGT and advance our understanding on the evolution of natural microbial communities within hosts.IMPORTANCEIn this study, to better identify horizontal gene transfer (HGT) in individual samples, we introduce a new co-barcoding sequencing system called metagenomics co-barcoding sequencing (MECOS), which has three significant improvements: (i) long DNA fragment extraction, (ii) a special transposome insertion, (iii) hybridization of DNA to barcode beads, and (4) an integrated bioinformatic pipeline. Using our approach, we have over 10-fold increased contig length compared to short-reads mNGS, and observed over 50-fold HGT events after we corrected the potential wrong HGT events. Our results indicate the presence of approximately 3,000 HGT blocks, involving roughly 6,000 genes and 100 taxonomic groups in individual samples. Notably, these HGT events are predominantly enriched in genes that confer tetracycline resistance via ribosomal protection. MECOS is a useful tool for investigating HGT and the evolution of natural microbial communities within hosts, thereby advancing our understanding of microbial ecology and evolution.