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Numerous studies have demonstrated that multiple intrinsic and extrinsic factors shape the structure and composition of gut microbiota in a host. The disorder of the gut microbiota may trigger various host diseases. Here, we collected fecal samples from wild-caught Japanese geckos (Gekko japonicus) and captive conspecifics fed with mealworms (mealworm-fed geckos) and fruit flies (fly-fed geckos), aiming to examine the dietary and sexual correlates of the gut microbiota. We used 16S rRNA gene sequencing technology to determine the composition of the gut microbiota. The dominant phyla with a mean relative abundance higher than 10% were Verrucomicrobiota, Bacteroidota, and Firmicutes. Gut microbial community richness and diversity were higher in mealworm-fed geckos than in wild geckos. Neither community evenness nor beta diversity of gut microbiota differed among wild, mealworm-fed, and fly-fed geckos. The beta rather than alpha diversity of gut microbiota was sex dependent. Based on the relative abundance of gut bacteria and their gene functions, we concluded that gut microbiota contributed more significantly to the host’s metabolic and immune functions. A higher diversity of gut microbiota in mealworm-fed geckos could result from higher chitin content in insects of the order Coleoptera. This study not only provides basic information about the gut microbiota of G. japonicus but also shows that gut microbiota correlates with dietary habits and sex in the species.

Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer1, 2–3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM deletion enhances CAR-NK cell effector function both in vitro and in vivo and increases resistance to tumour-induced immunosuppression after rechallenge. Mechanistically, we establish that induction of CREM is mediated by the PKA–CREB signalling pathway, which can be activated by immunoreceptor tyrosine-based activation motif signalling downstream of CAR activation or by interleukin-15. Finally, our findings reveal that CREM exerts its regulatory functions through epigenetic reprogramming of CAR-NK cells. Our results provide support for CREM as a therapeutic target to enhance the antitumour efficacy of CAR-NK cells.The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

We used wild-caught Japanese geckos (Gekko japonicus) and captive conspecifics fed with mealworms and fruit flies to study their differences in gut microbial structure and composition and sexual correlates of gut microbiota. Gut microbial community richness and diversity were higher in mealworm-fed geckos than in wild geckos. The beta rather than alpha diversity of gut microbiota was sex dependent. From this study, we know the following. First, dietary and sexual correlates of gut microbiota are evident in G. japonicus. Second, with respect to the composition of gut microbiota, G. japonicus is more similar to the common leopard gecko than other reptilian taxa. Third, the diversity of gut microbiota is higher in geckos ingesting food with a higher chitin content. Numerous studies have demonstrated that multiple intrinsic and extrinsic factors shape the structure and composition of gut microbiota in a host. The disorder of the gut microbiota may trigger various host diseases. Here, we collected fecal samples from wild-caught Japanese geckos (Gekko japonicus) and captive conspecifics fed with mealworms (mealworm-fed geckos) and fruit flies (fly-fed geckos), aiming to examine the dietary and sexual correlates of the gut microbiota. We used 16S rRNA gene sequencing technology to determine the composition of the gut microbiota. The dominant phyla with a mean relative abundance higher than 10% were Verrucomicrobiota, Bacteroidota, and Firmicutes. Gut microbial community richness and diversity were higher in mealworm-fed geckos than in wild geckos. Neither community evenness nor beta diversity of gut microbiota differed among wild, mealworm-fed, and fly-fed geckos. The beta rather than alpha diversity of gut microbiota was sex dependent. Based on the relative abundance of gut bacteria and their gene functions, we concluded that gut microbiota contributed more significantly to the host's metabolic and immune functions. A higher diversity of gut microbiota in mealworm-fed geckos could result from higher chitin content in insects of the order Coleoptera. This study not only provides basic information about the gut microbiota of G. japonicus but also shows that gut microbiota correlates with dietary habits and sex in the species.

Somatic cells can be reprogrammed into induced pluripotent stem cells （iPSCs） by defined factors. The low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limited the potential application of iPSCs. Here we report that Lithium （Li）, a drug used to treat mood disorders, greatly enhances iPSC generation from both mouse embryonic fibroblast and human umbilical vein endothelial cells. Li facilitates iPSC generation with one （Oct4） or two factors （OS or OK）. The effect of Li on promoting reprogramming only partially depends on its major target GSK3β Unlike other GSK3β inhibitors, Li not only increases the expression of Nanog, but also enhances the transcriptional activity of Nanog. We also found that Li exerts its effect by promoting epigenetic modifications via downregulation of LSD1, a H3K4-specific histone demethylase. Knocking down LSD1 partially mimics Li＇s effect in enhancing reprogramming. Our results not only provide a straightforward method to improve the iPSC generation efficiency, but also identified a histone demethylase as a critical modulator for somatic cell reprogramming.

Background： Some ultrasonographic （US） signs overlap between benign and malignant nodules. The purpose of this study was to raise a special US sign of benign thyroid nodules, termed the ＂onion skin-liked sign.＂ Methods： Twenty-seven patients with 27 nodules who shrank naturally and the ＂onion skin-liked sign＂ appeared on the final US images were enrolled in the study. The ultrasound characters and risk stratifications at the start and end of observation were compared. Then, thirty goiters with fibrosis and thirty papillary thyroid carcinomas （PTC） were randomly selected from the database of our hospital, matched the sizes of 27 nodules at the end point of observation. The differences of ＂onion skin-liked sign＂ between the two groups were analyzed. Results： The average duration of follow-up of 27 nodules was 24.0 ± 12.2 months （range, 12-65 months）. At the end of the follow-up, the size of the nodules decreased on average by 1.26 ± 0.82 cm （range, 0.3-3.4 cm） and calcification was found in 21 nodules, compared with only 2 nodules with calcification at the start of the follow-up. In addition, only negligible or no blood flow signal could be detected at the periphery of all the nodules and 100% （27/27） were high suspicion at the end of observation. In matched groups, all PTC showed high suspicion of malignancy, 18/30 （60%） goiters with fibrosis were high suspicion and 11/30 （37%） were intermediate suspicion. Twenty-two patients in the group of nodular fibrosis presented ＂onion skin-liked sign,＂ which was not shown in any patient of PTC group. The sensitivity, specificity, positive predictive value, and negative predictive value of ＂onion skin-liked sign＂ in predicting nodular goiter with fibrosis were 73.3%, 100%, 100%, and 78.9%, respectively. Conclusions： The ＂onion skin-liked sign＂ was a characteristic US feature of benign thyroid nodules detected in the follow-up of thyroid nodules. It is useful to differentiate PTCs and nodular goiters with fibrosis.

Aim： Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Aβ peptide toxicity in vitro. Methods： The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aβ1-40 （2 pmol/L）, and the cell viability was detected using a CCK8 assay. Results： A series of β-（1,4）-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 pmol/L β-（1,4）-D-mannobiose 6, β-（1,4）-D-mannotriose 9 or β-（1,4）-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aβ1-40-induced toxicity. The efficacies were similar to those caused by 10 pmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. Conclusion： Synthetic homogeneous short chain β-（1,4）-D-mannans shows neuroprotective effect against Aβ peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.

Representative pioneer tree root systems in the subtropical area of South China were examined with regard to their structure, underground stratification and biomass distribution. Excavation of skeleton roots and observation of fine roots of seven species including the Euphorbiaceae, Theaceae, Melastomataceae, Lauraceae and Fagaceae families was carried out. The results showed that： （1） Pioneer tree roots in the first stage of natural succession were of two types, one characterized by taproot system with bulky plagiotropic branches; the other characterized by flat root system with several tabular roots. The late mesophilous tree roots were characterized by one obvious taproot and tactic braches roots up and down. Shrub species roots were characterized by heart fibrous root type featured both by horizontally and transversally growing branches. Root shapes varied in different dominant species at different stages of succession. （2） Roots of the different species varied in the external features-color, periderm and structure of freshly cut slash. （3） In a set of successional stages the biomass of tree roots increased linearly with the age of growth. During monsoon, the total root biomass amounted to 115.70 t/ha in the evergreen broadqeaved forest; 50.61 t/ha in needle and broad-leaved mixed forest dominated by coniferous forest; and 64.20 t/ha in broad-and needle-leaved mixed forest dominated by broad-leaved heliophytes, and are comparable to the underground biomass observed in similar tropical forests. This is the first report about roots characteristics of forest in the lower sub-tropical area of Dinghushan, Guangdong, China.

Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality. The authors present an exciting 3D meta-holography based on angular spectrum diffraction theory that significantly improves depth limits. The showcased amorphous silicon metasurface with independent polarization control herein achieves a 47.5x depth increase and 0.95 dm depth reconstructions for polarization-independent and different color 3D meta-hologram.

A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD. A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR. As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression. BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism. ClinicalTrials.gov NCT00633282.

Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immune regulator STING (stimulator of interferon genes) confer remarkable protection against cancer pain, bone destruction, and local tumor burden. Repeated systemic administration of STING agonists robustly attenuates bone cancer-induced pain and improves locomotor function. Interestingly, STING agonists produce acute pain relief through direct neuronal modulation. Additionally, STING agonists protect against local bone destruction and reduce local tumor burden through modulation of osteoclast and immune cell function in the tumor microenvironment, providing long-term cancer pain relief. Finally, these in vivo effects are dependent on host-intrinsic STING and IFN-I signaling. Overall, STING activation provides unique advantages in controlling bone cancer pain through distinct and synergistic actions on nociceptors, immune cells, and osteoclasts. There is an unmet clinical need to develop therapies to alleviate metastatic bone pain, frequently observed in patients with advanced cancers. Here, using mouse models of bone cancer pain, the authors show that STING agonists not only suppress bone cancer tumor burden, but also attenuate bone pain and reduce cancer-induced bone destruction.