Anion Modulation of Ag-Imidazole Cuboctahedral Cage Microenvironments for Efficient Electrocatalytic CO2 Reduction.

How to achieve CO2 electroreduction in high efficiency is a current challenge with the mechanism not well understood yet. The metal-organic cages with multiple metal sites, tunable active centers, and well-defined microenvironments may provide a promising catalyst model. Here, we report self-assembly of Ag4L4 type cuboctahedral cages from coordination dynamic Ag+ ion and triangular imidazolyl ligand 1,3,5-tris(1-benzylbenzimidazol-2-yl) benzene (Ag-MOC-X, X= NO3, ClO4, BF4) via anion template effect. Notably, Ag-MOC-NO3 achieves the highest CO faradaic efficiency in pH-universal electrolytes of 86.1%(acidic), 94.1%(neutral) and 95.3% (alkaline), much higher than those of Ag-MOC-ClO4 and Ag-MOC-BF4 with just different counter anions. In situ attenuated total reflection Fourier transform infrared spectroscopy observes formation of vital intermediate *COOH for CO2-to-CO conversion. The density functional theory calculations suggest that the adsorption of CO2 on unsaturated Ag-site is stabilized by C-H⋅⋅⋅O hydrogen-bonding of CO2 in a microenvironment surrounded by three benzimidazole rings, and the activation of CO2 is dependent on the coordination dynamics of Ag-centers modulated by the hosted anions through Ag⋅⋅⋅X interactions. This work offers a supramolecular electrocatalytic strategy based on Ag-coordination geometry and host-guest interaction regulation of MOCs as high-efficient electrocatalysts for CO2 reduction to CO which is a key intermediate in chemical industry process.

Five undescribed meroterpenoids from Ganoderma lucidum and their inhibitory activities against renal fibrosis.

Five undescribed meroterpenoids, baosglucidnes A - E (1-5), were isolated from the fruiting bodies of Ganoderma lucidum. Among them, baosglucidne B (2) as a racemic mixture was obtained. Chiral HPLC was employed to separate a pair of enantiomers (+)-2 and (-)-2. The structures and stereochemical features of these substances were characterized by utilizing spectroscopic data and ECD calculations. Finally, the results of anti-renal fibrosis activity evaluation showed that baosglucidne E (5) could inhibit the expression of collagen I in TGF-ß1-induced rat kidney proximal tubular cells at 20 µM.

Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis.

Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.

Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema.

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including ( +)-camphoric acid, choline, adenosine, adenosine 5'-monophosphate, deoxyguanosine 5'-monophosphate, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-ß-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5'-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients.

Efficient pure-red perovskite light-emitting diodes with strong passivation via ultrasmall-sized molecules.

Perovskite light-emitting diodes (PeLEDs) have attracted great attention in recent years; however, the halogen vacancy defects in perovskite notably hamper the development of high-efficiency devices. Previously, large-sized passivation agents have been usually used, while the effect of defect passivation is limited due to the weak bonding or the large space steric hindrance. Here, we predict that the ultrasmall-sized formate (Fa) and acetate (Ac) have more efficient passivation ability because of the stronger binding with the perovskite, as demonstrated by density functional theory calculation. We introduce ultrasmall-sized cesium salts (CsFa/CsAc) into buried interface, which can also diffuse into the bulk, resulting in both buried interface and bulk passivation. In addition, the improved perovskite growth has been found due to the enhanced hydrophily after introducing CsFa/CsAc as additive. According to these advantages, a pure-red PeLED with 24.2% efficiency at 639 nm has been achieved.

Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E2 in the lateral parabrachial nucleus of male rats.

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

Zwitterionic Cellulose-based Polymer Electrolyte Enabled by Aqueous Solution Casting for High-performance Solid-state Batteries.

Polyethylene oxide (PEO)-based solid-state batteries hold great promise as the next-generation batteries with high energy density and high safety. However, PEO-based electrolytes encounter certain limitations, including inferior ionic conductivity, low Li+ transference number, and poor mechanical strength. Herein, we aim to simultaneously address these issues by utilizing one-dimensional zwitterionic cellulose nanofiber (ZCNF) as fillers for PEO-based electrolytes using a simple aqueous solution casting method. Multiple characterizations and theoretical calculations demonstrate that the unique zwitterionic structure imparts ZCNF with various functions, such as disrupting PEO crystallization, dissociating lithium salts, anchoring anions through cationic groups, accelerating Li+ migration by anionic groups, as well as its inherent reinforcement effect. As a result, the prepared PL-ZCNF electrolyte exhibits remarkable ionic conductivity (5.37 × 10-4 S cm-1) and Li+ transference number (0.62) at 60 °C without sacrificing mechanical strength (9.2 MPa), together with high critical current density of 1.1 mA cm-2. Attributed to these merits of PL-ZCNF, the LiFePO4|PL-ZCNF|Li solid-state full-cell delivers exceptional rate capability and cycling performance (900 cycles at 5 C). Notably, the assembled pouch-cell can maintain steady operation over 1000 cycles with an impressive 93.7% capacity retention at 0.5 C and 60 °C, highlighting the great potential of PL-ZCNF for practical applications.

"RNSP (Rannasangpei)" Rescued MK-801-induced Schizophrenia-like Behaviors in Mice via Oxidative Stress and BDNF-TrkB/Akt Pathway.

Schizophrenia (SCZ) is a complex, severe psychotic disorder that is highly persistent. Patients often cannot control their emotions and have delusions of victimization, world-weariness, and even suicide. Therefore, safer and more effective drugs are urgently needed. Rannasangpei (RNSP) from "the four medicine tantras" was used as a neuroprotective agent. The objective of this study was to investigate the effect and mechanism of RNSP on MK-801-induced SCZ in mice. Fifty C57BL/6J mice were randomly divided into a normal group, a model group, an RNSP group, a crocin (CRO) group, and an olanzapine (OLA) group, except for the normal group. The remaining mice were used to establish the MK-801-induced SCZ model. Changes in positive symptoms and cognitive impairment in mice before and after drug intervention were assessed by using the prepulse inhibition (PPI) test, Y-maze test (YMT), and open-field test (OFT). Intragastric administration of RNSP alleviated the symptoms of SCZ in SCZ mice, as demonstrated by the PPI, YMT, and OFT results. Compared with the model group, the first-line antipsychotic olanzapine reversed the anxiety-like phenotypes, hypermotility, and PPI deficits in the SCZ model mice. Further analysis revealed that RNSP reduced oxidative stress in SCZ model mice, as evidenced by increased superoxide dismutase (SOD) levels and decreased malondialdehyde (MDA) levels in the hippocampus, cortex, and blood of SCZ model mice. In our study, RNSP treatment restored the expression of brain-derived neurotrophic factor (BDNF), dopamine D2 receptor, p-Trkb, Akt/p-Akt, and doublecortin and inhibited the expression of IBA1 and Bax in the hippocampus of SCZ model mice. The polymerase chain reaction data indicated that RNSP treatment increased the expression of Bcl-2 and TGF-ß and decreased the expression of Bax, IL-1ß, and TNF-α in the brains of the model mice. Our results are the first to show that RNSP reverses SCZ-like behaviors in rodents (both positive symptoms and cognitive deficits) by reducing oxidative stress and activating the BDNF-TrkB/Akt pathway, suggesting that RNSP is a novel approach for treating SCZ.

Sequential radical and cationic reactivity at separated sites within one molecule in solution.

Distonic radical cations (DRCs) with spatially separated charge and radical sites are expected to show both radical and cationic reactivity at different sites within one molecule. However, such "dual" reactivity has rarely been observed in the condensed phase. Herein we report the isolation of crystalline 1λ2,3λ2-1-phosphonia-3-phosphinyl-cyclohex-4-enes 2a,b˙+, which can be considered delocalized DRCs and were completely characterized by crystallographic, spectroscopic, and computational methods. These DRCs contain a radical and cationic site with seven and six valence electrons, respectively, which are both stabilized via conjugation, yet remain spatially separated. They exhibit reactivity that differs from that of conventional radical cations (CRCs); specifically they show sequential radical and cationic reactivity at separated sites within one molecule in solution.

Graph neural network based on brain inspired forward-forward mechanism for motor imagery classification in brain-computer interfaces.

Introduction: Within the development of brain-computer interface (BCI) systems, it is crucial to consider the impact of brain network dynamics and neural signal transmission mechanisms on electroencephalogram-based motor imagery (MI-EEG) tasks. However, conventional deep learning (DL) methods cannot reflect the topological relationship among electrodes, thereby hindering the effective decoding of brain activity. Methods: Inspired by the concept of brain neuronal forward-forward (F-F) mechanism, a novel DL framework based on Graph Neural Network combined forward-forward mechanism (F-FGCN) is presented. F-FGCN framework aims to enhance EEG signal decoding performance by applying functional topological relationships and signal propagation mechanism. The fusion process involves converting the multi-channel EEG into a sequence of signals and constructing a network grounded on the Pearson correlation coeffcient, effectively representing the associations between channels. Our model initially pre-trains the Graph Convolutional Network (GCN), and fine-tunes the output layer to obtain the feature vector. Moreover, the F-F model is used for advanced feature extraction and classification. Results and discussion: Achievement of F-FGCN is assessed on the PhysioNet dataset for a four-class categorization, compared with various classical and state-of-the-art models. The learned features of the F-FGCN substantially amplify the performance of downstream classifiers, achieving the highest accuracy of 96.11% and 82.37% at the subject and group levels, respectively. Experimental results affirm the potency of FFGCN in enhancing EEG decoding performance, thus paving the way for BCI applications.

COVID-19 vaccinations for patients with epilepsy in Guizhou Province, China: A cross-sectional study.

Several COVID-19 vaccines have been approved for emergency use according to China's immunization programs. These vaccines has created hope for patients with epilepsy, because the vaccines can help to reduce their risk of becoming infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to investigate the COVID-19 vaccine safety in patients with epilepsy. Here, we assessed the time of symptom control and the features of adverse events of seizure patients following their COVID-19 vaccinations. The results showed that adverse events of COVID-19 vaccinations for epilepsy patients included local pain at the injection site, dizziness and headache, epileptic attack, somnolence, limb weakness, limb pain, allergy, and fever. In addition, the average recovery time of the adverse events was approximately 42 h. More importantly, our study showed that it was relatively safe to vaccinate epilepsy patients who did not experience seizures for approximately 12 months prior to the immunization date.

Identifying the geospatial relationship of surface ozone pollution in China: Implications for key pollution control regions.

Surface ozone pollution, as a pressing environmental concern, has garnered widespread attention across China. Due to air mass transport, effective control of ozone pollution is highly dependent on collaborative efforts across neighboring regions. However, specific regions with strong internal interactions of ozone pollution are not yet well identified. Here, we introduced the Geospatial SHapley Additive exPlanation (GeoSHAP) approach, which primarily involves machine learning and geostatistical algorithms. Based on extensive atmospheric environmental monitoring data from 2017 to 2021, machine learning models were employed to train and predict ozone concentrations at the target location. The R2 values on the test sets of different scale regions all reached 0.98 in the overall condition, indicating that the core model has good accuracy and generalization ability. The results highlight key regions with high ozone geospatial relationship (OGR) index, predominantly located in the Northern District (ND), spanning the Fen-Wei Plain, the Loess Plateau, and the North China Plain, as well as within portions of the Yangtze River Delta (YRD) and the Pearl River Delta (PRD). Further investigation indicated that high geospatial relationships stem from a synergy between anthropogenic and natural factors, with anthropogenic factors serving as a pivotal element. This study revealed key regions with the most urgent need for joint control of anthropogenic sources to mitigate ozone pollution.

Mitochondrial bioenergetics: coupling of transport to tubular mitochondrial metabolism.

PURPOSE OF REVIEW: Renal tubules have robust active transport and mitochondrial metabolism, which are functionally coupled to maintain energy homeostasis. Here, I review the current literature and our recent efforts to examine mitochondrial adaptation to different transport activities in renal tubules. RECENT FINDINGS: The advance of extracellular flux analysis (EFA) allows real-time assessments of mitochondrial respiration, glycolysis, and oxidation of energy substrates. We applied EFA assays to freshly isolated mouse proximal tubules, thick ascending limbs (TALs), and distal convoluted tubules (DCTs) and successfully differentiated their unique metabolic features. We found that TALs and DCTs adjusted their mitochondrial bioenergetics and biogenesis in response to acute and chronic alterations of transport activity. Based on the literature and our recent findings, I discuss working models and mechanisms underlying acute and chronic tubular adaptations to transport activity. The potential roles of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) are discussed. SUMMARY: Mitochondria in renal tubules are highly plastic to accommodate different transport activities. Understanding the mechanisms may improve the treatment of renal tubulopathies.

Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans.

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.

Five undescribed cyclopeptides from Cordyceps militaris.

Ustiloxins I-M (1-5), five undescribed cyclopeptides bearing a 15-membered macrocyclic skeleton, were isolated from Cordyceps militaris. The structures of 1 and 5 were identified by spectroscopic and crystallographic methods, whereas the structures of 2-4 were assigned by spectroscopic and computational approaches. Biological evaluation of all the compounds toward human triple-negative breast cancer cells revealed that compounds 4 and 5 are toxic with IC50 values of 64.29 µM and 28.89 µM, respectively.

Revealing the variances in color formation and bioactivities of seven catechin monomers throughout the enzymatic reaction by colorimetric and mass spectrometry.

The capacity differences of seven catechin monomers to produce colors after treating with catechin-free extract were investigated. After 240-min reaction, only (-)-epicatechin (EC) and (+)-catechin (C) presented obvious luminous red color with L* values of 63.32-71.73, a* values of 37.13-46.44, and b* values of 65.64-69.99. Meanwhile, the decrease rate of EC and C was 43.52 %-50.35 %, which were significantly lower than those of other catechin monomers (85.91 %-100 %). The oxidized products of catechin monomers were analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry coupled with diode array detector, wherein dehydro-dimers and -trimers (oxidative coupling products of catechins' A-B ring) were found to be the major chromogenic compounds of EC and C. Additionally, the antioxidant capacity of catechin monomers only decreased after 30-min reaction, while along with further enzymatic reaction, catechin monomers presented comparable oxyradical scavenging ability (e.g., the DPPH inhibitory rates of catechin monomers were in the range of 24.42 %-50.77 %) to vitamin C (positive control, DPPH inhibitory rate was 27.66 %). Meanwhile, the inhibitory effects of most catechin monomers on α-glucosidase were enhanced in different degrees. These results provided basis for the development of enzymatically-oxidized catechin monomers as functional food color additives.

Induction of neutralizing antibodies against SARS-CoV-2 variants by a multivalent mRNA-lipid nanoparticle vaccine encoding SARS-CoV-2/SARS-CoV Spike protein receptor-binding domains in mice.

To address the need for multivalent vaccines against Coronaviridae that can be rapidly developed and manufactured, we compared antibody responses against SARS-CoV, SARS-CoV-2, and several variants of concern in mice immunized with mRNA-lipid nanoparticle vaccines encoding homodimers or heterodimers of SARS-CoV/SARS-CoV-2 receptor-binding domains. All vaccine constructs induced robust anti-RBD antibody responses, and the heterodimeric vaccine elicited an IgG response capable of cross-neutralizing SARS-CoV, SARS-CoV-2 Wuhan-Hu-1, B.1.351 (beta), and B.1.617.2 (delta) variants.

In Vitro Comparative Analysis of the Effect and Structure-Based Influencing Factors of Flavonols on Lipid Accumulation.

Flavonols represented by quercetin have been widely reported to have biological activities of regulating lipid metabolism. However, the differences in flavonols with different structures in lipid-lowering activity and the influencing factors remain unclear. In this study, the stability, transmembrane uptake ratio, and lipid metabolism regulation activities of 12 flavonol compounds in the 3T3-L1 cell model were systematically compared. The results showed that kaempferide had the highest cellular uptake ratio and the most potent inhibitory effect on adipogenesis at a dosing concentration of 20 µM, followed by isorhamnetin and kaempferol. They inhibited TG accumulation by more than 65% and downregulated the expression of PPARγ and SREBP1c by more than 60%. The other four aglycones, including quercetin, did not exhibit significant activity due to the structural instability in the cell culture medium. Meanwhile, five quercetin glucosides were quite stable but showed a low uptake ratio that no obvious activity was observed. Correlation analysis also showed that for 11 compounds except galangin, the activity was positively correlated with the cellular uptake ratio (p < 0.05, r = 0.6349). These findings may provide a valuable idea and insight for exploring the structure-based activity of flavonoids at the cellular level.

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.