Dynamic changes of Bacterial Microbiomes in Oropharynx during Infection and Recovery of COVID-19 Omicron Variant.

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group-severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

Li5AlO4-Assisted Low-Temperature Sintering of Dense Li7La3Zr2O12 Solid Electrolyte with High Critical Current Density.

In recent years, solid electrolytes (SEs) have been developed a lot due to the superior safety of solid-state batteries (SSBs) upon liquid electrolyte-based commercial batteries. Among them, garnet-type Li7La3Zr2O12 (LLZO) is one of the few SEs that is stable to lithium anode with high Li+ conductivity and the feasibility of preparation under ambient air, which makes it a promising candidate for fabricating SSBs. However, high sintering temperature (>1200 °C) prevents its large-scale production, further hindering its application. In this work, the Li5AlO4 sintering aid is proposed to decrease the sintering temperature and modify the grain boundaries of LLZO ceramics. Li5AlO4 generates in situ Li2O atmosphere and molten Li-Al-O compounds at relatively low temperatures to facilitate the gas-liquid-solid material transportation among raw LLZO grains, which decreases the densification temperature over 150 °C and strengthens the grain boundaries against lithium dendrites. As an example, Ta-doped LLZO ceramics without excessive Li sintered with 2 wt % Li5AlO4 at 1050 °C delivered high relative density > 94%, an ionic conductivity of 6.7 × 10-4 S cm-1, and an excellent critical current density (CCD) of 1.5 mA cm-2 at room temperature. In comparison, Ta-doped LLZO with 15% excessive Li sintered at 1200 °C delivered low relative density < 89%, a low ionic conductivity of ∼2 × 10-4 S cm-1, and a poor CCD of 0.5 mA cm-2. Li symmetric cells and Li-LFP full cells fabricated with Li5AlO4-assised ceramics were stably cycled at 0.2 mA cm-2 over 2000 h and at 0.8C over 100 cycles, respectively.

Spin-torque-driven antiferromagnetic resonance.

The intrinsic fast dynamics make antiferromagnetic spintronics a promising avenue for faster data processing. Ultrafast antiferromagnetic resonance-generated spin current provides valuable access to antiferromagnetic spin dynamics. However, the inverse effect, spin-torque-driven antiferromagnetic resonance (ST-AFMR), which is attractive for practical utilization of fast devices but seriously impeded by difficulties in controlling and detecting Néel vectors, remains elusive. We observe ST-AFMR in Y3Fe5O12/α-Fe2O3/Pt at room temperature. The Néel vector oscillates and contributes to voltage signal owing to antiferromagnetic negative spin Hall magnetoresistance-induced spin rectification effect, which has the opposite sign to ferromagnets. The Néel vector in antiferromagnetic α-Fe2O3 is strongly coupled to the magnetization in Y3Fe5O12 buffer, resulting in the convenient control of Néel vectors. ST-AFMR experiment is bolstered by micromagnetic simulations, where both the Néel vector and the canted moment of α-Fe2O3 are in elliptic resonance. These findings shed light on the spin current-induced dynamics in antiferromagnets and represent a step toward electrically controlled antiferromagnetic terahertz emitters.

Integrating bioinformatics and experimental validation to unveil disulfidptosis-related lncRNAs as prognostic biomarker and therapeutic target in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) stands as a prevalent malignancy globally, characterized by significant morbidity and mortality. Despite continuous advancements in the treatment of HCC, the prognosis of patients with this cancer remains unsatisfactory. This study aims at constructing a disulfidoptosis­related long noncoding RNA (lncRNA) signature to probe the prognosis and personalized treatment of patients with HCC. METHODS: The data of patients with HCC were extracted from The Cancer Genome Atlas (TCGA) databases. Univariate, multivariate, and least absolute selection operator Cox regression analyses were performed to build a disulfidptosis-related lncRNAs (DRLs) signature. Kaplan-Meier plots were used to evaluate the prognosis of the patients with HCC. Functional enrichment analysis was used to identify key DRLs-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between the DRLs signature and immune microenvironment. The function of TMCC1-AS1 in HCC was validated in two HCC cell lines (HEP3B and HEPG2). RESULTS: We identified 11 prognostic DRLs from the TCGA dataset, three of which were selected to construct the prognostic signature of DRLs. We found that the survival time of low-risk patients was considerably longer than that of high-risk patients. We further observed that the composition and the function of immune cell subpopulations were significantly different between high- and low-risk groups. Additionally, we identified that sorafenib, 5-Fluorouracil, and doxorubicin displayed better responses in the low-score group than those in the high-score group, based on IC50 values. Finally, we confirmed that inhibition of TMCC1-AS1 impeded the proliferation, migration, and invasion of hepatocellular carcinoma cells. CONCLUSIONS: The DRL signatures have been shown to be a reliable prognostic and treatment response indicator in HCC patients. TMCC1-AS1 showed potential as a novel prognostic biomarker and therapeutic target for HCC.

Electrical 180° switching of Néel vector in spin-splitting antiferromagnet.

Antiferromagnetic spintronics have attracted wide attention due to its great potential in constructing ultradense and ultrafast antiferromagnetic memory that suits modern high-performance information technology. The electrical 180° switching of Néel vector is a long-term goal for developing electrical-controllable antiferromagnetic memory with opposite Néel vectors as binary "0" and "1." However, the state-of-art antiferromagnetic switching mechanisms have long been limited for 90° or 120° switching of Néel vector, which unavoidably require multiple writing channels that contradict ultradense integration. Here, we propose a deterministic switching mechanism based on spin-orbit torque with asymmetric energy barrier and experimentally achieve electrical 180° switching of spin-splitting antiferromagnet Mn5Si3. Such a 180° switching is read out by the Néel vector-induced anomalous Hall effect. On the basis of our writing and readout methods, we fabricate an antiferromagnet device with electrical-controllable high- and low-resistance states that accomplishes robust write and read cycles. Besides fundamental advance, our work promotes practical spin-splitting antiferromagnetic devices based on spin-splitting antiferromagnet.

Clinical Benefit of Avapritinib in KIT-Mutant Gastrointestinal Stromal Tumors: A Post Hoc Analysis of the Phase I NAVIGATOR and Phase I/II CS3007-001 Studies.

PURPOSE: The efficacy of the selective KIT/PDGFRA inhibitor avapritinib (300 mg once daily) was explored in patients with non-PDGFRA-mutant gastrointestinal stromal tumors (GISTs) from the phase I NAVIGATOR and phase I/II CS3007-001 trials. PATIENTS AND METHODS: Adults with unresectable/metastatic, KIT-only-mutant GISTs and progression following ≥1 tyrosine kinase inhibitors (TKIs) were included in this post hoc analysis. Baseline mutational status was identified in tumor and plasma. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent radiology review per modified RECIST v1.1 in patients harboring KIT activation-loop mutations (KIT exons 17 or 18) without ATP binding-pocket mutations (KIT exons 13 or 14; ALposABPneg), and other KIT mutations (OTHERS). RESULTS: Sixty KIT ALposABPneg and 100 KIT OTHERS predominantly heavily pretreated patients (61.3% with ≥3 prior TKIs) were included. ORR was significantly higher in KIT ALposABPneg than KIT OTHERS patients (unadjusted: 26.7% vs. 12.0%; P = 0.0852; adjusted: 31.4% vs. 12.1%; P = 0.0047). Median PFS (mPFS) was significantly longer in KIT ALposABPneg patients compared with KIT OTHERS patients (unadjusted: 9.1 vs. 3.5 months; P = 0.0002; adjusted: 9.1 vs. 3.4 months; P < 0.0001), and longer in second- versus later-line settings (19.3 vs. 5.6-10.6 months). Benefit with avapritinib was observed in patients with KIT exon 9 mutations in the ≥4 line settings (mPFS: 5.6 and 3.7 months for 4 line and >4 line, respectively). CONCLUSIONS: Avapritinib showed greater antitumor activity in patients with GISTs harboring KIT ALposABPneg mutations versus KIT OTHERS, and may be considered in the former subpopulation. Patients with KIT exon 9 mutations may also benefit in ≥4 line settings.

Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China.

AIM: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. METHODS: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). RESULTS: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). CONCLUSIONS: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.

CT features combined with RECIST 1.1 criteria improve progression assessments of sunitinib-treated gastrointestinal stromal tumors.

OBJECTIVES: To explore the auxiliary value of combining CT features with existing response evaluation criteria in the prediction of progressive disease (PD) in gastrointestinal stromal tumors (GIST) patients treated with sunitinib. MATERIAL AND METHODS: Eighty-one patients with GISTs who received sunitinib were included in this retrospective multicenter study and divided into training and external validation cohorts. Progression at six months was determined as a reference standard. The predictive performance of the RECIST 1.1 and Choi criteria was compared. CT features at baseline and the first follow-up were analyzed. Logistic regression analyses were used to determine the most significant predictors and develop modified criteria. RESULTS: A total of 216 lesions showed a good response and 107 showed a poor response in 81 patients. The RECIST 1.1 criteria performed better than the Choi criteria in predicting progression (AUC, 0.75 vs. 0.69, p = 0.04). The expanded/intensified high-enhancement area, blurred tumor-tissue interface, and progressive enlarged vessels feeding or draining the mass (EVFDM) differed significantly between lesions with good and poor responses in the training cohort (p = 0.001, 0.003, and 0.000, respectively). Multivariate analysis revealed that the expanded/intensified high-enhancement area (p = 0.001), progressive EVFDM (p = 0.000), and RECIST PD (p = 0.000) were independent predictive factors. Modified RECIST (mRECIST) criteria were developed and showed significantly higher AUCs in the training and external validation cohorts than the RECIST 1.1 criteria (training: 0.81 vs. 0.73, p = 0.002; validation: 0.82 vs. 0.77, p = 0.04). CONCLUSION: The mRECIST criteria, combining CT features with the RECIST 1.1 criteria, demonstrated superior performance in the prediction of early progression in GIST patients receiving sunitinib. CLINICAL RELEVANCE STATEMENT: The mRECIST criteria, which combine CT features with the RECIST 1.1 criteria, may facilitate the early detection of progressive disease in GIST patients treated with sunitinib, thereby potentially guiding the timely switch to late-line medications or combination with surgical excision. KEY POINTS: • The RECIST 1.1 criteria outperformed the Choi criteria in identifying progression of GISTs in patients treated with sunitinib. • GISTs displayed different morphologic features on CT depending on how they responded to sunitinib. • Combining CT morphologic features with the RECIST 1.1 criteria allowed for the prompt and accurate identification of progressing GIST lesions.

Mitochondrial Lipid Metabolism Genes as Diagnostic and Prognostic Indicators in Hepatocellular Carcinoma.

Background: Due to the heterogeneity of Hepatocellular carcinoma (HCC), there is an urgent need for reliable diagnosis and prognosis. Mitochondria-mediated abnormal lipid metabolism affects the occurrence and progression of HCC. Objective: This study aims to investigate the potential of mitochondrial lipid metabolism (MTLM) genes as diagnostic and independent prognostic biomarkers for HCC. Methods: MTLM genes were screened from the Gene Expression Omnibus (GEO) and Gene Set Enrichment Analysis (GSEA) databases, followed by an evaluation of their diagnostic values in both The Cancer Genome Atlas Program (TCGA) and the Affiliated Cancer Hospital of Guangxi Medical University (GXMU) cohort. The TCGA dataset was utilized to construct a gene signature and investigate the prognostic significance, immune infiltration, and copy number alterations. The validity of the prognostic signature was confirmed through GEO, International Cancer Genome Consortium (ICGC), and GXMU cohorts. Results: The diagnostic receiver operating characteristic (ROC) curve revealed that eight MTLM genes have excellent diagnostic of HCC. A prognostic signature comprising 5 MTLM genes with robust predictive value was constructed using the lasso regression algorithm based on TCGA data. The results of the Stepwise regression model showed that the combination of signature and routine clinical parameters had a higher area under the curve (AUC) compared to a single risk score. Further, a nomogram was constructed to predict the survival probability of HCC, and the calibration curves demonstrated a perfect predictive ability. Finally, the risk score also unveiled the different immune and mutation statuses between the two different risk groups. Conclusion: MTLT-related genes may serve as diagnostic and prognostic biomarkers for HCC as well as novel therapeutic targets, which may be beneficial for facilitating further understanding the molecular pathogenesis and providing potential therapeutic strategies for HCC.

Rapamycin extenuates experimental colitis by modulating the gut microbiota.

BACKGROUND AND AIM: Autophagy and gut microbiota correlates closely with the inflammatory bowel disease. Herein, we aimed to study the roles of rapamycin on the gut microbiota in inflammatory bowel disease. METHODS: Acute colitis was induced with dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzenesulfonic acid solution in mice. Mice were administered with rapamycin or hydroxychloroquine. Weight loss, disease activity index scores, histopathological score, serum inflammatory cytokines, intestinal permeability, and colonic autophagy-related proteins were detected. Cecal content was also preserved in liquid nitrogen and subsequently analyzed following the 16S DNA sequencing. The antibiotic cocktail-induced microbiome depletion was performed to further investigate the relationship between autophagy activation and gut microbiota. RESULTS: Compared with the control group, the colonic autophagy-related proteins of P62, mTOR, and p-mTOR increased significantly, while the levels of LC3B and ATG16L1 decreased (all P < 0.05) in the model group. After rapamycin intervention, the colonic pathology of mice improved, while the disease activity index score decreased substantially; the colon length increased, and the expression of IL-6 and TNF-α decreased. Following hydroxychloroquine treatment, some indicators suggested aggravation of colitis. Principal coordinates analysis showed that the DSS group was located on a separate branch from the rapamycin group but was closer to the hydroxychloroquine group. Compared with the DSS group, the rapamycin group was associated with higher abundances of f_Lactobacillaceae (P = 0.0151), f_Deferribacteraceae (P = 0.0290), g_Lactobacillus (P = 0.0151), g_Mucispirillum (P = 0.0137), s_Lactobacillus_reuteri (P = 0.0028), and s_Clostridium_sp_Culture_Jar-13 (P = 0.0082) and a lower abundance of s_Bacteroides_sartorii (P = 0.0180). Linear discriminant analysis effect size showed that rapamycin increased the abundances of Lactobacillus-reuteri, Prevotellaceae, Paraprevotella, Christensenella and Streptococcus and decreased those of Peptostreptococcaceae and Romboutsia Bacteroides-sartorii. Besides, the improvement effect of autophagy activation on colitis disappears following gut microbiome depletion. CONCLUSION: The therapeutic effects of rapamycin on extenuating experimental colitis may be related to the gut microbiota.

Mdivi1 ameliorates mitochondrial dysfunction in non-alcoholic steatohepatitis by inhibiting JNK/MFF signaling.

BACKGROUND AND AIMS: Mitochondrial dysfunction plays a crucial role in the progression of non-alcoholic steatohepatitis (NASH). Mitochondrial division inhibitor 1 (Mdivi1) is a potential inhibitor of dynamin-related protein (Drp1) and mitochondrial fission. However, the therapeutic effect of Mdivi1 against NASH and its underlying molecular mechanisms remain unclear. METHODS: In this study, we established mouse models of NASH by inducing high-fat/high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diets and treated the animals with 5 mg/kg/day Mdivi1 or placebo. RESULTS: Treatment with Mdivi1 significantly alleviated diet-induced fatty liver phenotypes, including increased liver weight/body weight ratio, insulin resistance, hepatic lipid accumulation, steatohepatitis, and liver injury. Furthermore, Mdivi1 treatment suppressed HFHC or MCD diet-induced changes in the expression of genes related to lipid metabolism and inflammatory cytokines. Additionally, Mdivi1 reduced macrophage infiltration in the injured liver and promoted polarization of macrophages towards the M1 phenotype. At the molecular level, Mdivi1 attenuated mitochondrial fission by reducing Drp1 activation and expression, thereby decreasing mitochondrial reactive oxygen species accumulation and mitochondrial DNA damage. Moreover, Mdivi1-treated mice exhibited elevated levels of phosphorylated-c-Jun N-terminal kinase (p-JNK), mitochondrial fission factor (MFF), cleaved caspase 3 protein, and TUNEL-positive cell expression in the liver, suggesting that Mdivi1 might ameliorate mitochondrial dysfunction and reduce hepatocyte apoptosis by inhibiting the JNK/MFF pathway. CONCLUSION: Collectively, Mdivi1 protected against diet-induced NASH by restoring mitochondrial homeostasis and function, potentially through its inhibitory effect on the JNK/MFF pathway. Consequently, further investigation of Mdivi1 as a promising drug for NASH treatment is warranted.

Hepatobiliary and pancreatic: Multi-donor fecal microbiota transplantation attenuated high-fat diet-induced hepatic steatosis in mice by remodeling the gut microbiota.

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) can improve the symptoms of nonalcoholic fatty liver disease (NAFLD) by restoring the gut microbiota. This study was aimed to evaluate the therapeutic effects of single-donor (SD) or multi-donor (MD) FMT in a mouse model of hepatic steatosis and explore the underlying mechanisms. METHODS: Fecal samples were collected from NAFLD patients and healthy controls with similar baseline characteristics, with gut microbiota analyzed. Mice were fed either a normal-chow diet (NCD) or a high-fat diet (HFD) for 3 weeks and then administered fecal microbiota collected from healthy SDs or MDs for 12 weeks. RESULTS: Fecal samples from NAFLD patients showed significantly lower microbial diversity than those from healthy controls. MD-FMT reduced liver fat accumulation and body weight and significantly improved serum and liver biochemical indices in HFD-fed mice. Compared to untreated HFD-fed mice, MD-FMT significantly decreased the relative expression of IL-1ß, IL-6, TNF-α, IFN-γ, and IL-1ß mRNAs in the liver. The relative protein level of intestinal barrier components, including claudin-1, occludin, and E-cadherin, as well as serum lipopolysaccharide (LPS) level in mice, were found to be improved following MD-FMT intervention. Furthermore, FMT reversed HFD-induced gut dysbiosis and increased the abundance of beneficial bacteria such as Blautia and Akkermansia. CONCLUSION: NAFLD patients and healthy controls showed distinct gut microbiota. Likewise, HFD altered gut microbiota in mice compared to NCD-fed controls. MD-FMT restored gut dysbiosis in HFD-fed mice and attenuated liver steatosis, and should be considered as an effective treatment option for NAFLD.

Two-photon imaging reveals histopathological changes in the gastric tumor microenvironment induced by neoadjuvant treatment.

There is a close association between tumor response and survival in gastric cancer patients after receiving neoadjuvant treatment. An accurate and rapid assessment of therapeutic efficacy would be helpful for subsequent treatments and individual prognosis. At present, pathological examination is the gold standard for evaluating treatment response, however, it requires additional staining and the process is tedious, labor-intensive, as well as time-consuming. Here, we introduce a label-free imaging technique, two-photon imaging, to evaluate histopathological changes induced by pre-operative therapy, with a focus on assessing tumor regression as well as stromal response. Imaging data show that two-photon imaging allows label-free, rapid visualization of various aspects of pathological alterations in tumor microenvironment such as fibrotic reaction, inflammatory cell infiltration, mucinous response, isolated residual tumor cells. Moreover, a semi-automatic image processing approach is developed to extract the collagen morphological features, and statistical results show that there are significant differences in collagen area, length, width, cross-link space between the gastric cancer tissues with and without treatment. With the advent of a portable, miniaturized two-photon imaging device, we have enough reason to believe that this technique will become as an important auxiliary diagnostic tool in assessing neoadjuvant treatment response and thereby tailoring the most appropriate therapy strategies for the patients.

Erratum: Long-Distance Coherent Propagation of High-Velocity Antiferromagnetic Spin Waves [Phys. Rev. Lett. 130, 096701 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.096701.

Ruderman-Kittel-Kasuya-Yosida-Type Interlayer Dzyaloshinskii-Moriya Interaction in Synthetic Magnets.

Conduction electron spins interacting with magnetic impurity spins can mediate an interlayer exchange interaction, namely, the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction. This discovery opened the way to significant technological developments in the field of magnetic storage and spintronics. So far, the RKKY-type interlayer interaction has been found to construct symmetric coupling of magnetism; however, the asymmetric counterpart remains unexplored. Here we report unprecedented RKKY-type interlayer Dzyaloshinskii-Moriya interaction (DMI) in synthetic magnets, exhibiting a damped oscillatory feature. This asymmetric interlayer interaction is found to be dramatically dependent on the intermediate coupling layer. By introducing the Fert-Lévy model to the trilayer system, we reveal that the in-plane inversion symmetry breaking plays a pivotal role for generating interlayer DMI and the RKKY oscillation is an intrinsic behavior in metallic multilayers. Our finding fills up the empty block for RKKY-type asymmetric interlayer exchange coupling in comparison to the well-known (symmetric) RKKY-type interlayer exchange coupling.

Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis.

BACKGROUND AND AIM: Mucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y-box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution. METHODS: We studied the characteristics of UXT-V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT-V1 in the colonic epithelium was investigated using lentivirus-mediated shRNA in vitro and ex vivo. Through endogenous Co-immunoprecipitation and LC-MS/MS, we identified ZONAB as a UXT-V1-interactive protein. RESULTS: Herein, we report that UXT-V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT-V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT-V1 in NCM-460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT-V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT-V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation-related genes, including AML1 and KLF4. CONCLUSION: Taken together, our study reveals a potential role of UXT-V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC.

Optimizing Li1.3Al0.3Ti1.7(PO4)3 Particle Sizes toward High Ionic Conductivity.

NASICON-type Li1.3Al0.3Ti1.7(PO4)3 (LATP) has attracted a lot of attention because of its high ionic conductivity and stability to air and moisture. However, the size effect of LATP primary particles on ionic conductivity is ignored. In this study, different sizes of LATP particles are prepared to investigate the morphology, relative density, and ionic conductivity of the LATP solid electrolyte. The influences of particle size and sintering temperature on the microstructure, phase composition, and electrical properties of LATP ceramics were systematically studied. The medium-sized LATP particle (2 µm) presents a great microstructure with a high relative density of over 97%, the highest ionic conductivity of 6.7 × 10-4 S cm-1, and an activation energy of 0.418 eV. The Li-Li symmetric cells and Li-LFP batteries delivering good electrochemical performance were fabricated with highly conductive LATP ceramics. These results make significant strides in elucidating the relationship between the particle sizes of LATP and its electrochemical performance.

Ordered creation and motion of skyrmions with surface acoustic wave.

Magnetic skyrmions with a well-defined spin texture have shown unprecedented potential for various spintronic applications owning to their topologically non-trivial and quasiparticle properties. To put skyrmions into practical technology, efficient manipulation, especially the inhibition of skyrmion Hall effect (SkHE) has been intensively pursued. In spite of the recent progress made on reducing SkHE in several substituted systems, such as ferrimagnets and synthetic antiferromagnets, the organized creation and current driven motion of skyrmions with negligible SkHE in ferromagnets remain challenging. Here, by embedding the [Co/Pd] multilayer into a surface acoustic wave (SAW) delay line where the longitudinal leaky SAW is excited to provide both the strain and thermal effect, we experimentally realized the ordered generation of magnetic skyrmions. The resultant current-induced skyrmions movement with negligible SkHE was observed, which can be attributed to the energy redistribution of the system during the excitation of SAW. Our findings open up an unprecedentedly new perspective for manipulating topological solitons, which could possibly trigger the future discoveries in skyrmionics and spin acousto-electronics.

Engineering siRNA-loaded and RGDfC-targeted selenium nanoparticles for highly efficient silencing of DCBLD2 gene for colorectal cancer treatment.

Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.