Indoxyl sulfate mediates low handgrip strength and is predictive of high hospitalization rates in patients with end-stage renal disease.

Background and aims: Sarcopenia has a higher occurrence rate in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Low handgrip strength-and not sarcopenia per se-is associated with clinical outcomes in patients with CKD, including cardiovascular mortality and hospitalization. The factors contributing to low handgrip strength are still unknown. Accordingly, this study aimed to determine whether uremic toxins influence low handgrip strength in patients with CKD. Materials and methods: This cohort study lasted from August 2018 to January 2020. The participants were divided into three groups: the control group [estimated glomerular filtration rate (eGFR) ≥ 60 ml/min], an advanced CKD group (eGFR = 15-60 ml/min), and an ESRD group (under maintenance renal replacement therapy). All participants underwent handgrip strength measurement, dual-energy X-ray absorptiometry, and blood sampling for myokines (irisin, myostatin, and interleukin 6) and indoxyl sulfate. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus as low appendicular skeletal muscle index (appendicular skeletal muscle/height2 of < 7.0 kg/m2 in men and < 5.4 kg/m2 in women) and low handgrip strength (< 28 kg in men and < 18 kg in women). Results: Among the study participants (control: n = 16; CKD: n = 17; and ESRD: n = 42), the ESRD group had the highest prevalence of low handgrip strength (41.6 vs. 25% and 5.85% in the control and CKD groups, respectively; p < 0.05). The sarcopenia rate was similar among the groups (12.5, 17.6, and 19.5% for the control, CKD, and ESRD groups, respectively; p = 0.864). Low handgrip strength was associated with high hospitalization rates within the total study population during the 600-day follow-up period (p = 0.02). The predictions for cardiovascular mortality and hospitalization were similar among patients with and without sarcopenia (p = 0.190 and p = 0.094). The serum concentrations of indoxyl sulfate were higher in the ESRD group (227.29 ± 92.65 µM vs. 41.97 ± 43.96 µM and 6.54 ± 3.45 µM for the CKD and control groups, respectively; p < 0.05). Myokine concentrations were similar among groups. Indoxyl sulfate was associated with low handgrip strength in univariate and multivariate logistic regression models [univariate odds ratio (OR): 3.485, 95% confidence interval (CI): 1.372-8.852, p = 0.001; multivariate OR: 8.525, 95% CI: 1.807-40.207, p = 0.007]. Conclusion: Handgrip strength was lower in the patients with ESRD, and low handgrip strength was predictive of hospitalization in the total study population. Indoxyl sulfate contributed to low handgrip strength and counteracted the benefits of myokines in patients with CKD.

Euchromatic histone lysine methyltransferase 2 facilitates radioresistance in prostate cancer by repressing endoplasmic reticulum protein 29 transcription.

Prostate cancer is one of the most common cancers in men. This study was conducted to investigate the role of euchromatic histone lysine methyltransferase 2 (EHMT2) and endoplasmic reticulum protein 29 (ERP29) in the progression of radioresistance in prostate cancer. The expression of EHMT2 and ERP29 in prostate cancer cells and during the progression of radioresistance was detected using quantitative reverse transcription-polymerase chain reaction and western blotting, and the interaction between EHMT2 and ERP29 was investigated. The proliferation of transfected cells under x-ray irradiation was determined using the methyl thiazolyl tetrazolium and colony formation assays. Flow cytometry was used to analyze the apoptosis of the transfected cells under x-ray irradiation. Nude mice were subcutaneously injected with prostate cancer (DU145) cells stably transfected with sh-ERP29 or sh-NC. The effect of ERP29 expression on radioresistance in nude mice was assessed by x-ray irradiation. The expression of EHMT2 was upregulated and that of ERP29 was downregulated in prostate cancer cells during radioresistance progression. EHMT2 downregulation suppressed radioresistance in DU145 and androgen-sensitive prostate cancer (LNCaP) cells. In irradiated DU145 cells, EHMT2 inhibition decreased the number of colonies and accelerated apoptosis. The transcription of ERP29 was suppressed by EHMT2 by upregulating H3K9me2 and downregulating H3K4me3, thereby regulating radioresistance in prostate cancer cells. In addition, the downregulation of ERP29 promoted the progression of radioresistance in prostate cancer cells in nude mice. EHMT2 promotes radioresistance in prostate cancer cells by repressing ERP29 transcription.

[Re-thinking the acupoint-visceral correlation: evidence from clinical literature and its biological mechanism].

The regularity of acupoint-viscera correlation is a basic problem in the study of acupuncture and moxibustion. At present, there are two main theories of the regularities: (1) the law of acupoint effect determined by meridian circulation; (2) segmental dominance of acupoint effect. These two regularities belong to different paradigm systems, they are not complementary relations within the same conceptual system. Based on the evidence of clinical practice of acupuncture and moxibustion, combined with the research on biological mechanisms, this paper analyzed the objectivity and universality of the regularities of acupoint-visceral correlation. The law determined by meridian of acupoint effect does not manifests the universality guiding role in the clinical practice of modern acupuncture and moxibustion, which is obviously divorced from the needs of modern clinical practice. The segmental dominance of acupoint effect has been strongly supported by the clinical practice of modern acupuncture and moxibustion, which is highly consistent with the clinical practice. The regularity of acupoint effect needs to be tested and re-identified in practice.

Mucoadhesive Hydrogel with Anti-gastric Acid and Sustained-Release Functions for Amelioration of DSS-Induced Ulcerative Colitis.

Mucoadhesive hydrogels with multifunctional properties such as gastric acid resistance and sustained drug release in the intestinal tract are highly desirable for the oral treatment of inflammatory bowel diseases (IBDs). Polyphenols are proven to have great efficacies compared with the first-line drugs for IBD treatments. We recently reported that gallic acid (GA) was capable of forming a hydrogel. However, this hydrogel is prone to easy degradation and poor adhesion in vivo. To tackle this problem, the current study introduced sodium alginate (SA) to form a gallic acid/sodium alginate hybrid hydrogel (GAS). As expected, the GAS hydrogel showed excellent antiacid, mucoadhesive, and sustained degradation properties in the intestinal tract. In vitro studies demonstrated that the GAS hydrogel significantly alleviated ulcerative colitis (UC) in mice. The colonic length of the GAS group (7.75 ± 0.38 cm) was significantly longer than that of the UC group (6.12 ± 0.25 cm). The disease activity index (DAI) value of the UC group was (5.5 ± 0.57), which was markedly higher than that of the GAS group (2.5 ± 0.65). The GAS hydrogel also could inhibit the expression of inflammatory cytokines, regulating macrophage polarization and improving the intestinal mucosal barrier functions. All these results indicated that the GAS hydrogel was an ideal candidate for oral treatment of UC.

Limosilactobacillus reuteri ameliorates preeclampsia in mice via improving gut dysbiosis and endothelial dysfunction.

BACKGROUND: As a leading cause of maternal and neonatal morbidity and mortality, preeclampsia (PE) remains enigmatic. We confirmed that PE is associated with gut dysbiosis. However, whether probiotics could improve PE via regulating gut microbiota remains unclear. Exploring specific probiotic that could alleviate PE by modulating gut microbiota and elucidating detailed mechanisms will be essential for treating PE. METHODS: PE model was induced by nitric oxide (NO) inhibition with L-NAME in mice, and treated with Limosilactobacillus reuteri (L. reuteri). 16 S rDNA analysis was conducted on feces from mice. In vitro and in vivo experiments were performed to explore the roles and mechanisms of L. reuteri in PE. RESULTS: NO inhibition by L-NAME induced PE and gut dysbiosis in mice, characterized by differential gut microbiome, reduced alpha diversity, and markedly decreased abundance of Lactobacillales and L. reuteri. Importantly, L. reuteri could improve PE induced by L-NAME in mice, and ameliorate the gut dysbiosis of PE mice, including restorative gut microbiota composition, increased alpha diversity, and upregulated L. reuteri content. Moreover, L. reuteri could improve NO synthesis, angiogenesis, inflammation and oxidative stress of PE mice. Consistently, L. reuteri could ameliorate NO synthesis, endothelial dysfunction and inflammation mediated by L-NAME in vitro. CONCLUSIONS: Our results reveal that L. reuteri could ameliorate PE induced by NO inhibition in mice via improving gut dysbiosis and endothelial dysfunction, supporting gut microbiota serving as therapeutic target for treating PE originated from endothelial dysfunction and L. reuteri protecting patients from PE via modulating gut microbiota and endothelial function.

Smart nanoparticles and microbeads for interventional embolization therapy of liver cancer: state of the art.

The process of transcatheter arterial chemoembolization is characterized by the ability to accurately deliver chemotherapy drugs with minimal systemic side effects and has become the standard treatment for unresectable intermediate hepatocellular carcinoma (HCC). However, this treatment option still has much room for improvement, one of which may be the introduction of nanomaterials, which exhibit unique functions and can be applied to in vivo tumor imaging and therapy. Several biodegradable and multifunctional nanomaterials and nanobeads have recently been developed and applied in the locoregional treatment of hepatocellular cancer. This review explores recent developments and findings in relation to micro-nano medicines in transarterial therapy for HCC, emerging strategies to improve the efficacy of delivering nano-based medicines, and expounding prospects for clinical applications of nanomaterials.

MiR-125b and SATB1-AS1 might be shear stress-mediated therapeutic targets.

The aim of the study was to explore the potential molecular mechanism associated with shear stress on abdominal aortic aneurysm (AAA) progression. This study performed RNA sequencing on AAA patients (SQ), AAA patients after endovascular aneurysm repair (EVAR, SH), and normal controls (NC). Furthermore, we identified the differentially expressed microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNA (cirRNAs) and constructed competing endogenous RNA (ceRNA) networks. Finally, 164 differentially expressed miRNAs, 179 co-differentially expressed lncRNAs, and 440 co-differentially expressed circRNAs among the three groups were obtained. The differentially expressed miRNAs mainly enriched in 325 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Target genes associated with co-differentially expressed genes among the group of SH, SQ, and NC mainly enriched in 66 KEGG pathways. LncRNA-miRNA-mRNA interactions, including 15 lncRNAs, 63 miRNAs and 57 mRNAs, was constructed. CircRNA-miRNA-mRNA ceRNA network included 79 circRNAs, 21 miRNAs, and 49 mRNAs. Among them, KLRC2 and CSTF1, targeted by miR-125b, participated in cell-mediated immunity regulation. MiR-320-related circRNAs and SATB1-AS1 serving as the sponge of miRNAs, such as has-circ-0129245, has-circ-0138746, and has-circ-0139786, were hub genes in ceRNA network. In conclusion, AAA patients might be benefit from EVAR based on various pathways and some molecules, such as miR-125b and SATB1-AS1, related with shear stress.

Dual-stimuli responsive smart nanoprobe for precise diagnosis and synergistic multi-modalities therapy of superficial squamous cell carcinoma.

BACKGROUND: Although the promising advancements of current therapeutic approaches is available for the squamous cell carcinoma (SCC) patients, the clinical treatment of SCC still faces many difficulties. The surgical irreparable disfigurement and the postoperative wound infection largely hamper the recovery, and the chemo/radiotherapy leads to toxic side effects. RESULTS: Herein, a novel pH/Hyaluronidase (HAase) dual-stimuli triggered smart nanoprobe FeIIITA@HA has been designed through the biomineralization of Fe3+ and polyphenol tannic acid (TA) under the control of hyaluronic acid (HA) matrix. With the HA residues on the outer surface, FeIIITA@HA nanoprobes can specifically target the SCC cells through the over-expressed CD44, and accumulate in the carcinoma region after intravenously administration. The abundant HAase in carcinoma microenvironment will trigger the degradation of HA molecules, thereby exposing the FeIIITA complex. After ingesting by tumor cells via CD44 mediated endocytosis, the acidic lysosomal condition will further trigger the protonation of TA molecules, finally leading to the Fe3+ release of nanoprobe, and inducing a hybrid ferroptosis/apoptosis of tumor cells through peroxidase activity and glutathione depletion. In addition, Owing to the outstanding T1 magnetic resonance imaging (MRI) performance and phototermal conversion efficiency of nanoprobes, the MRI-guided photothermal therapy (PTT) can be also combined to complement the Fe3+-induced cancer therapy. Meanwhile, it was also found that the nanoprobes can promote the recruitment of CD4+ and CD8+ T cells to inhibit the tumor growth through the cytokines secretion. In addition, the FeIIITA@HA nanoprobes can be eliminated from the body and no obvious adverse side effect can be found in histological analysis, which confirmed the biosafety of them. CONCLUSION: The current FeIIITA@HA nanoprobe has huge potential in clinical translation in the field of precise diagnosis and intelligent synergistic therapy of superficial SCC. This strategy will promisingly avoid the surgical defects, and reduce the systemic side effect of traditional chemotherapy, paving a new way for the future SCC treatment.

Short Mediterranean diet screener detects risk of prediabetes in Taiwan, a cross-sectional study.

We aimed to determine whether the 14-item Mediterranean diet adherence screener (MEDAS) is suitable in Taiwan and associate the MEDAS score with the risk of prediabetes. In this cross-sectional study 346 patients were recruited between 2014 and 2019 at Taipei Tzu Chi Hospital. The MEDAS score was obtained with a 14-item MEDAS used in the PREDIMED trial. The blood glucose level is measured by fasting glucose and HbA1c. The results of the screener were analyzed for internal consistency and compared with the blood glucose level using multivariate regression models. The MEDAS score was significantly (p = 0.001) and inversely associated with both measures of blood glucose level. Adjusted data (95% CI) showed that each additional point in the MEDAS score decreases the risk of prediabetes with abnormal fasting glucose (> 100 mg/dL) level by 60% and the risk of prediabetes with abnormal HbA1c (> 5.7%) by 22.4%. Consuming at least 3 servings of legumes each week was significantly (p = 0.007) related to a lower risk of prediabetes under logistic regression. A higher score on the 14-item MEDAS screener was significantly associated with a lower risk of prediabetes.

Decellularized-disc based allograft and xenograft prosthesis for the long-term precise reconstruction of temporomandibular joint disc.

Currently, no effective disc reconstruction treatment strategy is clinically available for temporomandibular joint (TMJ) disc-related diseases. To address this, we developed a prosthesis construct with laser-drilled decellularized natural disc reinforced by polycaprolactone, which mimics the natural morphology, and structural, biomechanical and biological property of the TMJ disc. The construct demonstrated good biocompatibility, safety and immunological tolerance both in vitro, and in a rat subcutaneous model. During 6 months implantation in an allogeneic rabbit TMJ disc reconstruction model, the disc prosthesis maintained its integrity, collagen fiber-orientation, mechanical property, joint structural stability and prevented articular cartilage and bone from damage. Furthermore, the "upgraded" disc prosthesis obtained from decellularized porcine disc was implanted into a goat TMJ disc reconstruction model. The xenograft prosthesis, with strength and viscoelasticity similar to a natural TMJ disc, was able to restore the structure and function of TMJ up to 20 weeks. These results demonstrate the translational feasibility of an allogeneic or xenogeneic decellularized disc prosthesis for treatment of advanced TMJ disc-related diseases. STATEMENT OF SIGNIFICANCE: This study makes a significant contribution to TMJ disc disease treatment both in theory and in clinics, because: (1) it provided an innovative approach to prepare an artificial TMJ disc with decent mechanical properties and long-term condyle-protecting effect; (2) it specified an advanced decellularized method for fibrocartilage decellularization and xenograft application; (3) it developed a facile and reproducible TMJ disc reconstruction model not only for middle size animal but also for large animal study; (4) the comprehensive and unreported biomechanical tests on the natural TMJ discs would act as a valuable reference for further research in the field of artificial TMJ disc materials or TMJ disc tissue engineering; (5) it suggested a potential treatment for patients with severe TMJ diseases that were commonly met but difficult to treat in clinics.

Mindfulness Training Improves Attention: Evidence from Behavioral and Event-related Potential Analyses.

Mindfulness meditation helps to improve attentional capacity. However, the neural correlates that indicate the mechanism through which mindfulness improves attention are unclear. To address this gap, we aimed to assess the effects of mindfulness training on sustained attentional capacity. Event-related potentials (ERPs) associated with the modified sustained attention response task (mSART) were used in this study. A total of 45 college students were randomly assigned to either the mindfulness group (n = 21) or the control group (n = 24). Participants in the mindfulness group received a three-week mindfulness training. The self-report results showed that the mindfulness group reported higher mindfulness scores (observing and non-judgment of inner experiences) after the training. The mindfulness group also scored lower on the state anxiety than the control group. Behavioral results also showed that self-caught mind wandering in the mindfulness group significantly decreased after the training, and the mindfulness group showed a faster response after the training. The ERP results showed that N2 amplitudes in the post-test were significantly greater than those in the pre-test in the mindfulness group. We did not find any interactions between group and time for P3. The findings suggest that mindfulness training can effectively improve sustained attentional capacity, as indicated by reduced mind wandering and increased N2 responses.

Stereodivergent Construction of 1,3-Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction.

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition of dialkylzinc reagents to cyclic enones with iridium-catalyzed asymmetric allylic substitution reaction. Good to excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction of adjacent stereocenters (1,2-position) reported in the literature, the current reaction can achieve the stereodivergent construction of nonadjacent stereocenters (1,3-position) by a proper combination of two chiral catalysts with different enantiomers.

Nanoprobe Based on Biominerals in Protein Corona for Dual-Modality MR Imaging and Therapy of Tumors.

Various functional nanomaterials have been fabricated as diagnostic and therapeutic nanomedicines; however, the nanoparticles closely interact with proteins when immersed in biological fluids, forming a "protein corona" that critically alters the biological identity of nanomedicine. Here, we developed a robust strategy to construct theranostic nanoprobes based on protein-corona-coated Fe3O4 nanoparticles and biomineralization in the corona. Water-soluble carboxylic Fe3O4 nanoparticles were prepared by treating oleate-capped Fe3O4 nanoparticles with Lemieux-von Rudloff reagent. Bovine serum albumin (BSA) was used as a model protein to form a corona on the surface of Fe3O4 nanoparticles, endowing the Fe3O4 nanoparticles with biocompatibility and nonimmunogenicity. The protein corona also provides a template for biomimetic mineralization of Fe3+ with tannic acid (TA) to construct Fe3O4@BSA-TAFeIII nanoprobes. The TA-Fe(III) biominerals can not only act as photothermal therapy agents but also interact with unsaturated transferrin in plasma to form a "hybrid" corona, enabling the nanoprobes to target tumor cells through the mediation of transferrin receptors, which commonly overexpress on tumor cell membranes. Once taken in by tumor cells, the protonation of phenol hydroxyl groups in acidic lysosomes would lead to the release of Fe3+, inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. In addition, the released Fe3+ can boost the T1-weighted MR imaging performance, and the Fe3O4 nanoparticles serve as T2-weighted MR imaging contrast agents. It is thus believed that the current nanoprobes can realize the enhanced dual-modality MR imaging and combined therapy of tumors through controlling the protein corona and biomineralization.

Unexpected spontaneous symmetry breaking and diverse ferroicity in two-dimensional mono-metal phosphorus chalcogenides.

Mono-metal phosphorus trichalcogenides (MPX3) have attracted intensive interest due to their intriguing magnetic properties and potential applications. Generally, single-layer two-dimensional (2D) MPX3 are believed to be centrosymmetric. However, we discovered that unexpected spontaneous symmetry breaking may occur in some 2D MPX3, i.e., vertical P-P dimers move out of the plane and become tilted, leading to the structural stability being enhanced, the inversion symmetry being simultaneously broken, and ferroelectricity or ferroelasticity emerging. By systematically investigating the family (176) of 2D MPX3, we found that 34 members undergo such symmetry breaking during geometric optimization, in which ten are identified to be dynamically stable. We show that the mismatch between the triangular sublattice of P-P dimers and the hexagonal sublattice of M atoms and the variable accommodation of P lone-pair electrons in different valence states of M atoms play dominant roles in the inversion symmetry breaking and the emergence of ferroicity. We obtained a ferroic atlas of the whole 2D MPX3 family, which also includes many stable antiferromagnetic and non-ferroic members that have never been reported. Our work not only presents ferroelectricity in the 2D MPX3 family but also reveals how diverse ferroicity emerges with various spontaneous symmetry breakings, which will be helpful for further exploration of 2D ferroic materials.

Photonic Crystal-Integrated Optoelectronic Devices with Naked-Eye Visualization and Digital Readout for High-Resolution Detection of Ultratrace Analytes.

The detection of ultratrace analytes is highly desirable for the non-invasive monitoring of human diseases. However, a major challenge is fast, naked-eye, high-resolution ultratrace detection. Herein, a rectangular 3D composite photonic crystal (PC)-based optoelectronic device is first designed that combines the sensitivity-enhancing effects of PCs and optoelectronic devices with fast and real-time digital monitoring. A crack-free, centimeter-scale, mechanically robust ellipsoidal composite PCs with sufficient hardness and modulus, even exceeding most plastics and aluminum alloys, are developed. The high mechanical strength of ellipsoidal composite PCs allows them to be hand-machined into rectangular geometries that can be conformally covered with the centimeter-scale flat light-detection area without interference from ambient light, easily integrating 3D composite PC-based optoelectronic devices. The PC-based device's signal-to-noise ratio increases dramatically from original 30-40 to ≈60-70 dB. Droplets of ultratrace analytes on the device are identified by fast digital readout within seconds, with detection limits down to 5 µL, enabling rapid identification of ultratrace glucose in artificial sweat and diabetes risk. The developed 3D PC-based sensor offers the advantages of small size, low cost, and high reliability, paving the way for wider implementation in other portable optoelectronic devices.

Novel Small-Molecule PD-L1 Inhibitor Induces PD-L1 Internalization and Optimizes the Immune Microenvironment.

Blocking the PD-1/PD-L1 interaction has become an important strategy for tumor therapy, which has shown outstanding therapeutic effects in clinical settings. However, unsatisfactory response rates and immune-related adverse effects limit the use of anti-PD1/PD-L1 antibodies. Here, we report the discovery and identification of S4-1, an innovative small-molecule inhibitor of PD-L1. In vitro, S4-1 effectively altered the PD-L1/PD-1 interaction, induced PD-L1 dimerization and internalization, improved its localization to endoplasmic reticulum, and thus enhanced the cytotoxicity of peripheral blood mononuclear cells toward tumor cells. In vivo, S4-1 significantly inhibited tumor growth in both lung and colorectal cancer models, particularly in colorectal cancer, where it led to complete clearance of a portion of the tumor cells. Furthermore, S4-1 induced T-cell activation and inversed the inhibitory tumor microenvironment, consistent with the PD-L1/PD-1 pathway blockade. These data support the continued evaluation of S4-1 as an alternative ICB therapeutic strategy.

Mitochondrial E3 ubiquitin ligase MARCH5 is required for mouse oocyte meiotic maturation†.

As the most abundant organelles in oocytes, mitochondria play an important role in maintaining oocyte quality. Here, we report that March5, encoding a mitochondrial ubiquitin ligase that promotes mitochondrial elongation, plays a critical role in mouse oocyte meiotic maturation via regulating mitochondrial function. The subcellular localization of MARCH5 was similar to the mitochondrial distribution during mouse oocyte meiotic progression. Knockdown of March5 caused decreased ratios of the first polar body extrusion. March5-siRNA injection resulted in oocyte mitochondrial dysfunctions, manifested by increased reactive oxygen species, decreased ATP content as well as decreased mitochondrial membrane potential, leading to reduced ability of spindle formation and an increased ratio of kinetochore-microtubule detachment. Further study showed that the continuous activation of the spindle assembly checkpoint and the failure of Cyclin B1 degradation caused MI arrest and first polar body (PB1) extrusion failure in March5 knockdown oocytes. Taken together, our results demonstrated that March5 plays an essential role in mouse oocyte meiotic maturation, possibly via regulation of mitochondrial function and/or ubiquitination of microtubule dynamics- or cell cycle-regulating proteins.

Two-Dimensional Intercalating Multiferroics with Strong Magnetoelectric Coupling.

Intrinsic two-dimensional (2D) multiferroics that couple ferromagnetism and ferroelectricity are rare. Here, we present an approach to achieve 2D multiferroics using powerful intercalation technology. In this approach, metal atoms such as Cu or Ag atoms are intercalated in bilayer CrI3 to form Cu(CrI3)4 or Ag(CrI3)4. The intercalant leads to the inversion symmetry breaking and produces a large out-of-plane electric polarization with a low transition barrier and a small reversal electric field, exhibiting excellent 2D ferroelectric properties. In addition, due to charge transfer between the intercalated atoms and bilayer CrI3, the interlayer coupling transits from antiferromagnetic to ferromagnetic, and the intralayer ferromagnetic coupling is also enhanced. Furthermore, the built-in electric polarization causes a distinct surface magnetization difference, generating a strong magnetoelectric coupling with a coefficient larger than that of Fe, Co, and Ni thin films. Our work paves a practical path for 2D multiferroics, which may have crucial applications in spintronics.

An embedded interfacial network stabilizes inorganic CsPbI3 perovskite thin films.

The black perovskite phase of CsPbI3 is promising for optoelectronic applications; however, it is unstable under ambient conditions, transforming within minutes into an optically inactive yellow phase, a fact that has so far prevented its widespread adoption. Here we use coarse photolithography to embed a PbI2-based interfacial microstructure into otherwise-unstable CsPbI3 perovskite thin films and devices. Films fitted with a tessellating microgrid are rendered resistant to moisture-triggered decay and exhibit enhanced long-term stability of the black phase (beyond 2.5 years in a dry environment), due to increasing the phase transition energy barrier and limiting the spread of potential yellow phase formation to structurally isolated domains of the grid. This stabilizing effect is readily achieved at the device level, where unencapsulated CsPbI3 perovskite photodetectors display ambient-stable operation. These findings provide insights into the nature of phase destabilization in emerging CsPbI3 perovskite devices and demonstrate an effective stabilization procedure which is entirely orthogonal to existing approaches.