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Rational design and constructing earth-abundant electrocatalysts for efficient electrocatalytic water splitting is a crucial challenge. Herein, we report a simple and efficient one-step electrochemical synthetic route of the NiFe2O4@FeOOH composite electrocatalyst for the oxygen evolution reaction. The unique morphology of the NiFe2O4 nanoflowers loaded on FeOOH nanosheets allows more active sites to be exposed and promote charge transfer as well as gas release, and the resulting electrode enables a current density of 10 mA cm−2 at a low overpotential of 255 mV with outstanding stability at a current density of 100 mA cm−2 for 300 h.

The recent advancement of nanocatalysis offers great promise for cancer therapy, and the development of efficient nanozymes for catalytic biological reactions is highly desirable, but still challenging. Herein, we report the synthesis of ultra-small FeO x nanozymes which is enabled by the introduction of Cu 2+ . The obtained nanozymes exhibit versatile catalytic activities integratively for effective cancer treatment. In particular, the as-synthesized nanozymes display pH-dependent peroxidase (POD)-like catalytic activity and approach the optimal performance at around pH = 4, endowing it with the possibility for the precise treatment of tumors with acidic microenvironment. Furthermore, the FeO x nanozyme possesses a promising glutathione (GSH) depleting capability and allows to reverse the abnormal GSH level in the tumor issues. Additionally, the fabricated nanozymes are able to catalyze the decomposition of hydrogen peroxide (H 2 O 2 ) to O 2 , allowing to alleviate the hypoxic environment of the tumors and improving the function of immune system for the treatment of tumors. More importantly, the FeO x nanozymes showed remarkable stability and maintained the enzymatic activity after six months in storage. Collectively, the FeO x nanozyme was demonstrated as a promisingly effective nanomedicine for tumor treatment by 4T1 cells, providing insight into the rational design of efficient nanozymes for cancer treatment. Graphical abstract

Rational design and constructing earth-abundant electrocatalysts for efficient electrocatalytic water splitting is a crucial challenge. Herein, we report a simple and efficient one-step electrochemical synthetic route of the NiFe[sub.2]O[sub.4]@FeOOH composite electrocatalyst for the oxygen evolution reaction. The unique morphology of the NiFe[sub.2]O[sub.4] nanoflowers loaded on FeOOH nanosheets allows more active sites to be exposed and promote charge transfer as well as gas release, and the resulting electrode enables a current density of 10 mA cm[sup.−2] at a low overpotential of 255 mV with outstanding stability at a current density of 100 mA cm[sup.−2] for 300 h.

Antithymocyte globulin （ATG） is often included in the conditioning regimen to prevent graft vs. host disease in allogeneic hematopoietic stem cell （HSC） transplantation. However, because ATG contains antibodies targeting a wide range of antigens on human cells, its potential off-target effects remain a concern. Here, we explored this question in humanized mice that permit the analysis of human cell depletion in tissues. We showed that ATG binds to almost all lineages of human hematopoietic cells including HSCs, and accordingly it is capable of depleting almost all human hematopoietic cells. Interestingly, the efficacy of ATG was highly variable depending on the tissue of residence, with human cells in bone marrow significantly less susceptible than those in the blood and spleen. Recovery of multilineage human lymphohematopoietic reconstitution in humanized mice that received ATG 3 weeks after HSC transplantation indicates that ATG had a minimal effect on human HSCs that have settled in bone marrow niches. However, efficient human HSC depletion and engraftment failure were seen in mice receiving ATG at the time of transplantation. Our data indicate that the efficacy of ATG is tissue-dependent, and suggest a potential risk of impairing donor hematopoietic engraftment when ATG is used in preparative conditioning regimens.

An association between assisted reproductive technology （ART） and neurobehavioral imprinting disorders has been reported in many studies, and it seems that ART may interfere with imprint reprogramming. However, it has never been explored whether epigenetic erros or imprinting disease susceptibility induced by ART can be inherited transgenerationally. Hence, the aim of this study was to determine the effect of in vitro fertilization and embryo transfer （IVF-ET） on transgenerational inheritance in am inbred mouse model. Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations. Their behavior, morphology, histology, and DNA methylation status at several important differentially methylated regions （DMRs） were analyzed by Morris water maze, hematoxylin and eosin （H＆E） staining, and bisulfite genomic sequencing. No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF （F1） and female and male line F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation （0.40±0.118, P=0.086）. Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR displayed normal patterns. Methylation percentage did not differ significantly from that of adults conceived naturally, and the expression of the genes they regulated was not disturbed. Transgenerational integrity, such as behavior, morphology, histology, and DNA methylation status, was maintained in these generations, which indicates that exposure of female germ cells to hormonel stimulation and gamete manipulation might not affect the individuals and their descendents.

Bacteria preferentially accumulating in tumor microenvironments can be utilized as natural vehicles for tumor targeting. However, neither current chemical nor genetic approaches alone can fully satisfy the requirements on both stability and high efficiency. Here, we propose a strategy of “charging” bacteria with a nano-photocatalyst to strengthen their metabolic activities. Carbon nitride (C 3 N 4 ) is combined with Escherichia coli ( E. coli ) carrying nitric oxide (NO) generation enzymes for photo-controlled bacterial metabolite therapy (PMT). Under light irradiation, photoelectrons produced by C 3 N 4 can be transferred to E. coli to promote the enzymatic reduction of endogenous NO 3 – to cytotoxic NO with a 37-fold increase. In a mouse model, C 3 N 4 loaded bacteria are perfectly accumulated throughout the tumor and the PMT treatment results in around 80% inhibition of tumor growth. Thus, synthetic materials-remodeled microorganism may be used to regulate focal microenvironments and increase therapeutic efficiency. Targeting tumors with bacteria as vehicles for metabolite therapy suffers from low efficiency and robustness. Here, the authors combine carbon nitride with nitric oxide generation enzyme-positive E. coli for photo-controlled metabolite therapy (PMT) and observe increased effects both in vitro and in tumor-bearing mice.

The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy. Immune checkpoint blockade (ICB) immunotherapy efficacy has still limitations. Here, the authors generate a vaccine that integrates CD274 siRNA into the L1 protein of human papillomavirus, which cooperates with ICB by activating innate immunity in breast cancer models.

The microbiota in the human gut is strongly correlated with the progression of colorectal cancer (CRC) and with therapeutic responses to CRC. Here, by leveraging the higher concentration of the pro-tumoural Fusobacterium nucleatum and the absence of antineoplastic butyrate-producing bacteria in the faecal microbiota of patients with CRC, we show that—in mice with orthotopic colorectal tumours or with spontaneously formed colorectal tumours—oral or intravenous administration of irinotecan-loaded dextran nanoparticles covalently linked to azide-modified phages that inhibit the growth of F. nucleatum significantly augments the efficiency of first-line chemotherapy treatments of CRC. We also show that oral administration of the phage-guided irinotecan-loaded nanoparticles in piglets led to negligible changes in haemocyte counts, immunoglobulin and histamine levels, and liver and renal functions. Phage-guided nanotechnology for the modulation of the gut microbiota might inspire new approaches for the treatment of CRC. Dextran nanoparticles loaded with a chemotherapeutic agent and bound to phages that eliminate a pro-tumoural gut bacterium and promote the growth of anticancer-compound-producing bacteria boost chemotherapy responses in mouse models of colorectal cancer.

Intracytoplasmic sperm injection （ICSI） is commonly used to solve male infertility problems. Previous studies showed that early environmental exposure of an embryo may influence postnatal development. To detect whether ICSI operations affect the reproductive health of a male or his offspring, we established assisted reproductive technologies （ART） conceived mouse models, and analyzed gene expression profiles in the testes of both ICSI and naturally conceived （NC） newborn F~ mice using micro-array analysis. Among the differentially expressed genes, we focused on the expression of eight mate reproduction-related genes. Quantitative real-time reverse transcription- polymerase chain reaction （qRT-PCR） was used to analyze the expression of these genes in the testes of both adult and old F~ generation mice and adult F2 generation mice. Our results showed that down-regulated and somatic cell-expressed genes in newborn mice retained their differential expression patterns in adult and old F~ generation individuals, implying the persistence and fetal origin of the alteration in the expression of these genes. The intergen- erational transmission of differential gene expression was observed, but most changes tended to be reduced in adult F2 generations. Controlled ovarian hyperstimulation （COH） and in vitro fertilization （IVF） mice models were added to explore the precise factors contributing to the differences in ICSI offspring. The data demonstrated that superovulation, in vitro culture, and mechanical stimulation involved in ICSI had a cumulative effect on the differential expression of these male reproductive genes.

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects. An orally delivered encapsulated bacterial cocktail that metabolizes blood nitrogenous waste products in the gut reduces urea and creatinine concentrations in the blood of animal models of acute and chronic kidney injury.