Large-scale genome sequencing of giant pandas improves the understanding of population structure and future conservation initiatives.

The extinction risk of the giant panda has been demoted from "endangered" to "vulnerable" on the International Union for Conservation of Nature Red List, but its habitat is more fragmented than ever before, resulting in 33 isolated giant panda populations according to the fourth national survey released by the Chinese government. Further comprehensive investigations of the genetic background and in-depth assessments of the conservation status of wild populations are still necessary and urgently needed. Here, we sequenced the genomes of 612 giant pandas with an average depth of ~26× and generated a high-resolution map of genomic variation with more than 20 million variants covering wild individuals from six mountain ranges and captive representatives in China. We identified distinct genetic clusters within the Minshan population by performing a fine-grained genetic structure. The estimation of inbreeding and genetic load associated with historical population dynamics suggested that future conservation efforts should pay special attention to the Qinling and Liangshan populations. Releasing captive individuals with a genetic background similar to the recipient population appears to be an advantageous genetic rescue strategy for recovering the wild giant panda populations, as this approach introduces fewer deleterious mutations into the wild population than mating with differentiated lineages. These findings emphasize the superiority of large-scale population genomics to provide precise guidelines for future conservation of the giant panda.

Mitochondrial targeting sequence of magnetoreceptor MagR: More than just targeting.

Iron-sulfur clusters are essential cofactors for proteins involved in various biological processes, such as electron transport, biosynthetic reactions, DNA repair, and gene expression regulation. Iron-sulfur cluster assembly protein IscA1 (or MagR) is found within the mitochondria of most eukaryotes. Magnetoreceptor (MagR) is a highly conserved A-type iron and iron-sulfur cluster-binding protein, characterized by two distinct types of iron-sulfur clusters, [2Fe-2S] and [3Fe-4S], each conferring unique magnetic properties. MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome (Cry) and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation. Although the N-terminal sequences of MagR vary among species, their specific function remains unknown. In the present study, we found that the N-terminal sequences of pigeon MagR, previously thought to serve as a mitochondrial targeting signal (MTS), were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound. Moreover, the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex. Thus, the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting. These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.

Helical-caging enables single-emitted large asymmetric full-color circularly polarized luminescence.

Colorful circularly polarized luminescence materials are desired for 3D displays, information security and asymmetric synthesis, in which single-emitted materials are ideal owing to self-absorption avoidance, evenly entire-visible-spectrum-covered photon emission and facile device fabrication. However, restricted by the synthesis of chiral broad-luminescent emitters, the realization and application of high-performing single-emitted full-color circularly polarized luminescence is in its infancy. Here, we disclose a single-emitted full-color circularly polarized luminescence system (spiral full-color emission generator), composed of whole-vis-spectrum emissive quantum dots and chiral liquid crystals. The system achieves a maximum luminescence dissymmetry factor of 0.8 and remains an order of 10-1 in visible region by tuning its photonic bandgap. We then expand it to a series of desired customized-color circularly polarized luminescence, build chiral devices and further demonstrate the working scenario in the photoinduced enantioselective polymerization. This work contributes to the design and synthesis of efficient chiroptical materials, device fabrication and photoinduced asymmetric synthesis.

Unexpected divergence in magnetoreceptor MagR from robin and pigeon linked to two sequence variations.

Birds exhibit extraordinary mobility and remarkable navigational skills, obtaining guidance cues from the Earth's magnetic field for orientation and long-distance movement. Bird species also show tremendous diversity in navigation strategies, with considerable differences even within the same taxa and among individuals from the same population. The highly conserved iron and iron-sulfur cluster binding magnetoreceptor (MagR) protein is suggested to enable animals, including birds, to detect the geomagnetic field and navigate accordingly. Notably, MagR is also implicated in other functions, such as electron transfer and biogenesis of iron-sulfur clusters, raising the question of whether variability exists in its biochemical and biophysical features among species, particularly birds. In the current study, we conducted a comparative analysis of MagR from two different bird species, including the migratory European robin and the homing pigeon. Sequence alignment revealed an extremely high degree of similarity between the MagRs of these species, with only three sequence variations. Nevertheless, two of these variations underpinned significant differences in metal binding capacity, oligomeric state, and magnetic properties. These findings offer compelling evidence for the marked differences in MagR between the two avian species, potentially explaining how a highly conserved protein can mediate such diverse functions.

Genome assembly and annotation of the Brown-Spotted Pit viper Protobothrops mucrosquamatus.

The Brown-Spotted Pit viper (Protobothrops mucrosquamatus), also known as the Chinese habu, is a widespread and highly venomous snake distributed from Northeastern India to Eastern China. Genomics research can contribute to our understanding of venom components and natural selection in vipers. Here, we collected, sequenced and assembled the genome of a male P. mucrosquamatus individual from China. We generated a highly continuous reference genome, with a length of 1.53 Gb and 41.18% of repeat elements content. Using this genome, we identified 24,799 genes, 97.97% of which could be annotated. We verified the validity of our genome assembly and annotation process by generating a phylogenetic tree based on the nuclear genome single-copy genes of six other reptile species. The results of our research will contribute to future studies on Protobothrops biology and the genetic basis of snake venom.

Processable circularly polarized luminescence material enables flexible stereoscopic 3D imaging.

Endowing three-dimensional (3D) displays with flexibility drives innovation in the next-generation wearable and smart electronic technology. Printing circularly polarized luminescence (CPL) materials on stretchable panels gives the chance to build desired flexible stereoscopic displays: CPL provides unusual optical rotation characteristics to achieve the considerable contrast ratio and wide viewing angle. However, the lack of printable, intense circularly polarized optical materials suitable for flexible processing hinders the implementation of flexible 3D devices. Here, we report a controllable and macroscopic production of printable CPL-active photonic paints using a designed confining helical co-assembly strategy, achieving a maximum luminescence dissymmetry factor (glum) value of 1.6. We print customized graphics and meter-long luminous coatings with these paints on a range of substates such as polypropylene, cotton fabric, and polyester fabric. We then demonstrate a flexible textile 3D display panel with two printed sets of pixel arrays based on the orthogonal CPL emission, which lays an efficient framework for future intelligent displays and clothing.

Development and validation of a nomogram to predict protein-energy wasting in patients with peritoneal dialysis: a multicenter cohort study.

Background: Protein-energy wasting (PEW) is a common complication in patients with peritoneal dialysis (PD). Few investigations involved risk factors identification and predictive model construction related to PEW. We aimed to develop a nomogram to predict PEW risk in patients with peritoneal dialysis. Methods: We collected data from end-stage renal disease (ESRD) patients who regularly underwent peritoneal dialysis between January 2011 and November 2022 at two hospitals retrospectively. The outcome of the nomogram was PEW. Multivariate logistic regression screened predictors and established a nomogram. We measured the predictive performance based on discrimination ability, calibration, and clinical utility. Evaluation indicators were receiver operating characteristic (ROC), calibrate curve, and decision curve analysis (DCA). The performance calculation of the internal validation cohort validated the nomogram. Results: In this study, 369 enrolled patients were divided into development (n = 210) and validation (n = 159) cohorts according to the proportion of 6:4. The incidence of PEW was 49.86%. Predictors were age, dialysis duration, glucose, C-reactive protein (CRP), creatinine clearance rate (Ccr), serum creatinine (Scr), serum calcium, and triglyceride (TG). These variables showed a good discriminate performance in development and validation cohorts (ROC = 0.769, 95% CI [0.705-0.832], ROC = 0.669, 95% CI [0.585-0.753]). This nomogram was adequately calibrated. The predicted probability was consistent with the observed outcome. Conclusion: This nomogram can predict the risk of PEW in patients with PD and provide valuable evidence for PEW prevention and decision-making.

Multimodal-Responsive Circularly Polarized Luminescence Security Materials.

Nations, industries, and aspects of everyday life have undergone forgery and counterfeiting ever since the emergence of commercialization. Securing documents and products with anticounterfeit additives shows promise for authentication, allowing one to combat ever-increasing global counterfeiting. One most-used effective encryption strategy is to combine with optical-security markers on the required protection objects; however, state-of-the-art labels still suffer from imitation due to their poor complexity and easy forecasting, as a result of deterministic production. Developing advanced anticounterfeiting tags with unusual optical characters and further incorporating complex security features are desired to achieve multimodal, unbreakable authentication capacity; unfortunately, this has not yet been achieved. Here, we prepare a series of stable circularly polarized luminescence (CPL) materials, composed of toxicity-free, high-quality-emitting inorganic quantum dots (QDs) and liquid crystals, using a designed helical-coassembly strategy. This CPL system achieves a figure of merit (FM, assessing the performance of both luminescence dissymmetry and quantum yield) value of 0.39, fulfilling practical demands for anticounterfeiting applications. Based on these CPL structures, we produce a type of multimodal-responsive security materials (MRSMs) that exhibits six different stimuli-responsive modes, including light activation, polarization, temperature, voltage, pressure, and view angle. Thus, we show a proof-of-principle blockchain-like integrated anticounterfeiting system, allowing multimodal-responsive, interactive/changeable information encryption-decryption. We further encapsulate the obtained security materials into a fiber to expand our materials to work on flexible fabrics, that is, building an intelligent textile with a color-adaptable function along with environmental change.

Towards magnetism in pigeon MagR: Iron- and iron-sulfur binding work indispensably and synergistically.

The ability to navigate long distances is essential for many animals to locate shelter, food, and breeding grounds. Magnetic sense has evolved in various migratory and homing species to orient them based on the geomagnetic field. A highly conserved iron-sulfur cluster assembly protein IscA is proposed as an animal magnetoreceptor (MagR). Iron-sulfur cluster binding is also suggested to play an essential role in MagR magnetism and is thus critical in animal magnetoreception. In the current study, we provide evidence for distinct iron binding and iron-sulfur cluster binding in MagR in pigeons, an avian species that relies on the geomagnetic field for navigation and homing. Pigeon MagR showed significantly higher total iron content from both iron- and iron-sulfur binding. Y65 in pigeon MagR was shown to directly mediate mononuclear iron binding, and its mutation abolished iron-binding capacity of the protein. Surprisingly, both iron binding and iron-sulfur binding demonstrated synergistic effects, and thus appear to be integral and indispensable to pigeon MagR magnetism. These results not only extend our current understanding of the origin and complexity of MagR magnetism, but also imply a possible molecular explanation for the huge diversity in animal magnetoreception.

The rational design of iron-sulfur cluster binding site for prolonged stability in magnetoreceptor MagR.

Iron-sulfur proteins play essential roles in a wide variety of cellular processes such as respiration, photosynthesis, nitrogen fixation and magnetoreception. The stability of iron-sulfur clusters varies significantly between anaerobic and aerobic conditions due to their intrinsic sensitivity to oxygen. Iron-sulfur proteins are well suited to various practical applications as molecular redox sensors or molecular "wires" for electron transfer. Various technologies have been developed recently using one particular iron-sulfur protein, MagR, as a magnetic tag. However, the limited protein stability and low magnetic sensitivity of MagR hindered its wide application. Here in this study, the iron-sulfur binding site of pigeon clMagR was rationally re-designed. One such mutation, T57C in pigeon MagR, showed improved iron-sulfur binding efficiency and higher iron content, as well as prolonged thermostability. Thus, clMagRT57C can serve as a prototype for further design of more stable and sensitive magnetic toolbox for magnetogenetics in the future.

Modified hollow mesoporous silica nanoparticles as immune adjuvant-nanocarriers for photodynamically enhanced cancer immunotherapy.

Nanomedicine has demonstrated great potential in enhancing cancer immunotherapy. However, nanoparticle (NP)-based immunotherapy still has limitations in inducing effective antitumor responses and inhibiting tumor metastasis. Herein, polyethylenimine (PEI) hybrid thin shell hollow mesoporous silica NPs (THMSNs) were applied as adjuvant-nanocarriers and encapsulated with very small dose of photosensitizer chlorine e6 (Ce6) to realize the synergy of photodynamic therapy (PDT)/immunotherapy. Through PEI etching, the obtained Ce6@THMSNs exhibited enhanced cellular internalization and endosome/lysosome escape, which further improved the PDT efficacy of Ce6@THMSNs in destroying tumor cells. After PDT treatment, the released tumor-associated antigens with the help of THMSNs as adjuvants promoted dendritic cells maturation, which further boosted CD8+ cytotoxic T lymphocytes activation and triggered antitumor immune responses. The in vivo experiments demonstrated the significant potency of Ce6@THMSNs-based PDT in obliterating primary tumors and inducing persistent tumor-specific immune responses, thus preventing distant metastasis. Therefore, we offer a THMSNs-mediated and PDT-triggered nanotherapeutic system with immunogenic property, which can elicit robust antitumor immunity and is promising for future clinical development of immunotherapy.

Amplifying inorganic chirality using liquid crystals.

Chiral inorganic nanostructures have drawn extensive attention thanks to their unique physical properties as well as multidisciplinary applications. Amplifying inorganic chirality using liquid crystals (LCs) is an efficient way to enhance the parented inorganic asymmetry owing to chirality transfer. Herein, the universal synthetic methods and structural characterizations of chiral inorganic-doped LC hybrids are introduced. Additionally, the current progress and status of recent experiment and theory research about chiral interactions between inorganic nanomaterials (e.g. metal, semiconductor, perovskite, and magnetic oxide) and LCs are summarized in this review. We further present representative applications of these new hybrids in the area of encryption, sensing, optics, etc. Finally, we provide perspectives on this field in terms of material variety, new synthesis, and future practice. It is envisaged that LCs will act as a pivotal part in the amplification of inorganic chirality with versatile applications.

miR-3677-3p promotes hepatocellular carcinoma progression via inhibiting GSK3ß.

MicroRNAs play important roles in regulating hepatocellular carcinoma (HCC) formation, progression and metastasis. However, their functions and the underlying molecular mechanisms are still unclear. Here, we found that miR-3677-3p was highly expressed in primary tumor tissues of HCC patients. And its inhibition by using sponge in HCC cells could suppress cell proliferation significantly, but it has no effect on cell apoptosis. Through directly targeting to the 3' untranslated region of glycogen synthase kinase 3-ß (GSK3ß), miR-3677-3p could inhibit GSK3ß expression. Our study revealed that the miR-3677-3p/GSK3ß axis may play a crucial role in HCC and miR-3677-3p may serve as a potential diagnostic biomarker or a therapeutic target for HCC.

[Adjuvant therapy of Wentong acupuncture for elderly patients of primary osteoporosis with intestinal dysfunction: a randomized controlled trial].

OBJECTIVE: To observe the effects of Wentong acupuncture on bone mineral density (BMD), bone metabolism and intestinal function in elderly patients of primary osteoporosis with intestinal dysfunction. METHODS: A total of 128 elderly patients of primary osteoporosis with intestinal dysfunction were randomly divided into an observation group and a control group, 64 cases in each group. Patients in the control group were treated with oral administration of vitamin D calcium chewable tablets (0.6 g, once a day) and calcitriol capsules (0.25 µg, three times a day); the treatment was given for 6 months. On the basis of the treatment in the control group, patients in the observation group were additionally treated with Wentong acupuncture at Shenshu (BL 23), Mingmen (GV 4), Pishu (BL 20), Dachangshu (BL 25), Tianshu (ST 25) and Zusanli (ST 36), etc. for 30 min each time, once a day. After 1-week treatment, the patients took a rest for 2 days; the treatment was given for 6 months. Before and after treatment, the BMD of lumbar spine, femoral neck and femoral trochanter was detected by dual energy X-ray absorptiometry, and the serum levels of bone alkaline phosphatase (NBAP), osteocalcin (OC), matrix metalloproteinase-2 (MMP-2) and calcitonin (CT) were detected by ELISA method. The primary symptom scores of intestinal function, serum diamine oxidase (DAO) and D-lactic acid (D-Lac) levels were compared between the two groups before and after treatment, and the clinical efficacy of the two groups was evaluated. RESULTS: The total effective rate was 85.9% (55/64) in the observation group, which was higher than 71.9% (46/64) in the control group (P<0.05). After treatment, BMD were increased (P<0.05), and serum bone metabolism indexes were improved in the two groups (P<0.05); the BMD and serum bone metabolism indexes in the observation group were better than those in the control group (P<0.05). After treatment, the primary symptom scores of intestinal function, serum DAO and D-Lac levels in the observation group were decreased (P<0.05), and the indexes in the observation group were lower than those in the control group (P<0.05). CONCLUSION: The adjuvant therapy of Wentong acupuncture could increase BMD, improve bone metabolism and regulate intestinal function in elderly patients of primary osteoporosis with intestinal dysfunction.

Abemaciclib induces apoptosis in cardiomyocytes by activating the Hippo signaling pathway.

Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor that has received approval from the US Food and Drug Administration for using in patients with advanced breast cancer. However, its potential adverse effects on cardiomyocytes remain unknown. In this study, we used the cell counting kit-8 assay, western blot analysis, flow cytometry, immunostaining, and quantitative polymerase chain reaction to investigate the role of abemaciclib in inducing apoptosis and in inhibiting the viability and proliferation of AC16 human cardiomyocyte cells. The results revealed that abemaciclib induced apoptosis and inhibited cell proliferation by activating the Hippo signaling pathway. This work demonstrates the molecular basis by which abemaciclib induces cardiac side effects, providing a theoretical basis and effective targets for the treatment of cardiac diseases.

Pyrroloquinoline quinone attenuates isoproterenol hydrochloride­induced cardiac hypertrophy in AC16 cells by inhibiting the NF­κB signaling pathway.

Pyrroloquinoline quinone (PQQ) is a naturally occurring redox co­factor that functions as an essential nutrient and antioxidant, and has been reported to exert potent anti­inflammatory effects. However, the therapeutic potential of PQQ for isoproterenol hydrochloride (Iso)­induced cardiac hypertrophy has not yet been explored, at least to the best of our knowledge. In the present study, the anti­inflammatory effects of PQQ were investigated in Iso­treated AC16 cells, a myocardial injury cellular model characterized by an increase in the apparent surface area of the cells and the activation of intracellular cardiac hypertrophy­associated proteins. The results revealed that pre­treatment with PQQ significantly inhibited the expression of cardiac hypertrophy marker proteins, such as atrial natriuretic peptide, brain natriuretic peptide and ß­myosin heavy chain. PQQ also inhibited the activation of the nuclear factor (NF)­κB signaling pathway in Iso­treated AC16 cells, thus inhibiting the nuclear translocation of NF­κB and reducing the phosphorylation levels of p65. On the whole, the findings of this study suggest that PQQ may be a promising therapeutic agent for effectively reversing the progression of cardiac hypertrophy.

A Comprehensive Review of the Genus Pyrola Herbs in Traditional Uses, Phytochemistry and Pharmacological Activities.

Pyrola (Pyrolaceae), also known as Luxiancao/in China, was recorded in Sheng Nong's Herbal Classic listed in top grade. Pyrola herbs were used as medicinal plants for a long history with wide-ranging activities such as nourishing kidney-yang, strengthening muscles and bones, activating blood, stopping bleeding, dispelling rheumatism, and eliminating dampness. Currently, the research on Pyrola plants is increasing year by year but there is no comprehensive and detailed review concerning genus Pyrola. This review aims to sum up the updated and comprehensive information about botany and traditional use, phytochemistry, pharmacological activities and safety by analyzing the information available on Pyrola plants via internationally accepted scientific databases. Collectively, more than 100 compounds have been isolated from the Pyrola plants. Furthermore, a total of 33 prescriptions containing Pyrola plants are compiled in this review. Pyrola plants are used as indispensable agents in traditional Chinese medicine due to its activities of antimicrobial, anti-inflammatory, antioxidant, lipidlowering, cardiovascular and cerebrovascular protection, proliferation of osteoblasts promoting, antineoplastic and etc. Further work should be developed on the elucidation of structure-function relationship, understanding of multi-target pharmacological effects, as well as developing its application both in clinical usage and functional food for research and development of Pyrola plants.

Polyethylenimine Hybrid Thin-Shell Hollow Mesoporous Silica Nanoparticles as Vaccine Self-Adjuvants for Cancer Immunotherapy.

Conventional adjuvants (e.g., aluminum) are insufficient to trigger cell-mediated immunity, which plays a crucial role in triggering specific immunity against cancer. Therefore, developing appropriate adjuvants for cancer vaccines is a central way to stimulate the antitumor immune response. Hollow mesoporous silica nanoparticles (HMSNs) have been proven to stimulate Th1 antitumor immunity in vivo and promote immunological memory in the formulation of novel cancer vaccines. Yet, immune response rates of existing HMSNs for anticancer immunity still remain low. Here, we demonstrate the generation of polyethylenimine (PEI)-incorporated thin-shell HMSNs (THMSNs) through a facile PEI etching strategy for cancer immunotherapy. Interestingly, incorporation of PEI and thin-shell hollow structures of THMSNs not only improved the antigen-loading efficacy and sustained drug release profiles but also enhanced the phagocytosis efficiency by dendritic cells (DCs), enabled DC maturation and Th1 immunity, and sustained immunological memory, resulting in the enhancement of the adjuvant effect of THMSNs. Moreover, THMSNs vaccines without significant side effects can significantly reduce the potentiality of tumor growth and metastasis in tumor challenge and rechallenge models, respectively. THMSNs are considered to be promising vehicles and excellent adjuvants for the formulation of cancer vaccines for immunotherapy.

Au Nanocage-Strengthened Dissolving Microneedles for Chemo-Photothermal Combined Therapy of Superficial Skin Tumors.

For superficial skin tumors (SST) with high incidence, surgery and systemic therapy are relatively invasive and possible to cause severe side effect, respectively. Yet, topical therapy is confronted with the limited transdermal capacity because of the stratum corneum barrier layer of skin. Therefore, it is crucial to develop a highly effective and minimally invasive alternative transdermal approach for treating SST. Here, we developed gold nanocage (AuNC)- and chemotherapeutic drug doxorubicin (DOX)-loaded hyaluronic acid dissolving microneedle (MN) arrays. The loaded AuNCs are not only reinforcers to enhance the mechanical strength of the MNs, but also effective agents for photothermal therapy to obtain effective transdermal therapy for SST. The resultant MNs can effectively penetrate the skin, dissolve in the skin and release cargoes within the tumor site. Photothermal effect of AuNCs initiated by near-infrared laser irradiation combined with the chemotherapy effect of DOX destroyed tumors synergistically. Moreover, we verified the potent antitumor effects of the DOX/AuNC-loaded MNs after four administrations to SST-bearing mice without obvious side effects. Therefore, the drug/AuNC-loaded dissolving MN system provides a promising platform for effective, safe, minimally invasive combined treatment of SST.

Regulation of eIF2α expression and renal interstitial fibrosis by resveratrol in rat renal tissue after unilateral ureteral obstruction.

PURPOSE: This study was performed to assess the effect of resveratrol on the expression of eukaryotic initiation factor 2α (eIF2α) and activating transcription factor 4 (ATF4) in renal tissues of rats with unilateral ureteral obstruction (UUO). METHODS: Using UUO animal model, after 14 days of surgery, pathological changes were detected by HE staining, renal tubular damage index, renal interstitial collagen deposition area were evaluated by Masson staining, in situ cell apoptosis in renal tissue was analyzed by TUNEL assay, and protein expression of eIF2α and ATF4 in renal tissue was analyzed using western blot detection. RESULTS: After comparison of the treatment groups with model group, we observed that the degree of renal tubular damage, relative area of renal interstitial collagen and eIF2α, ATF4 protein expression were also significantly reduced (p<0.05, p <0.01) in the high-dose resveratrol group. CONCLUSION: Resveratrol can reduce the level of eIF2α protein expression, which further reduces the ATF4 levels.