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Abstract Patients diagnosed with diffuse large B-cell lymphoma (DLBCL) are at increased risk of developing atrial fibrillation (AF). Abnormal P-wave parameters (PWPs) have been identified as independent predictors of AF, however, their prognostic significance in DLBCL patients remains unknown. Newly diagnosed DLBCL patients from January 2015 to August 2022 were retrospectively included in this study. Patients were devided as with abnormal PWPs or without it. Primary outcome was the all-cause mortality. The median duration of follow-up was 16.3 months. The Kaplan‒Meier method and multivariable COX proportional hazards regression models were used to analyze the relationship between PWPs and all-cause mortality. Logistic regression analyses were performed to identify risk factors associated with PWPs. A total of 374 newly diagnosed DLBCL patients were included, of whom 137 patients exhibited abnormalities in PWPs. Compared to the group with normal PWPs, patients with PWPs abnormalities had a higher proportion of males (p = 0.001), elevated levels of blood urea nitrogen (p = 0.038) and blood creatinine (p = 0.005), and a higher rate of all-cause mortality (p = 0.001). PWPs, particularly P-wave duration (p = 0.017) and P-wave terminal force in lead V1 (PTFV1) (p = 0.001), were independently correlated with all-cause mortality in DLBCL patients. Furthermore, male patients exhibited a higher susceptibility to abnormal PWPs (p = 0.001). PWPs, particularly P-wave duration and PTFV1, serve as simple yet effective prognostic indicators for all-cause mortality in DLBCL patients. Consequently, vigilant monitoring of PWPs, particularly in male patients, is warranted to accurately evaluate the prognosis of DLBCL.

Surface nano-modification has emerged as an effective strategy to enhance osseointegration of titanium (Ti) implants. Despite its promise, rational optimization of surface nanomorphology for ameliorated osseointegration remains a significant challenge. Our research pioneering developed a one-step alkali etching technique to produce a gradient nanowire coating with continuously varied dimensions on Ti surfaces, which was subsequently served as a versatile platform for high-throughput screening of optimal dimensions to enhance osseointegration. The results showed that macrophages (MФs) that mainly governed the initial inflammatory reaction exhibited a polarization tendency towards pro-healing M2 phenotype with decreased nanowire dimension due to nanomorphology-mediated focal adhesion formation and activation of its downstream signaling pathways (typically PI3K-Akt). Simultaneously, small-sized nanowires with diameter of 5.63–14.25 nm and inter-spacing of 29.42–57.97 nm were conductive to angiogenesis of endothelial cells (ECs) and osteogenesis of bone marrow mesenchymal stem cells (BMSCs), which may share similar mechanisms of MФs. The in vivo results well corroborated these in vitro observations. The knowledge gained from the present work not only advance our understanding of the interaction between surface morphology and cells, but also potentially pave the way for efficient and cost-effective design of advanced biomaterial surfaces for better osseointegration.

Climate change adaptation policies and research have traditionally focused on dietary quantity, neglecting dietary quality, particularly in developing countries like Afghanistan. This study aims to identify how climate change affects household dietary diversity and whether the impacts are consistent across different food groups. To examine the impact of climate change on dietary diversity in Afghanistan, a climate change proxy variable (temperature) was created at the district level by calculating the difference from its long-term mean. Meanwhile, the Household Dietary Diversity Score (HDDS) was obtained from three rounds of household survey data conducted between 2011 and 2017, which included information from 60,099 households. Negative binomial regression analysis reveals a positive association between climate change and HDDS. That is, higher temperatures would lead to the higher availability of diverse diets in Afghanistan. Interestingly, climate change appears to affect food groups heterogeneously. While staple food consumption frequency remains unaffected, non-staple food consumption increases with higher temperatures. The results remain consistent after incorporating precipitation and two lagged versions of temperature and precipitation into the model. Therefore, the climate adaptation policies of the government of Afghanistan should consider different policy implications for staple and non-staple foods. These findings have policy implications for achieving food security and climate change-related Sustainable Development Goals (SDGs) such as SDG 2 (zero hunger) and SDG 13 (climate action).

Background: Diabetic bone healing remains a great challenge due to its pathological features including biochemical disturbance, excessive inflammation, and reduced blood vessel formation. In previous studies, small intestine submucosa (SIS) has been demonstrated for its immunomodulatory and angiogenic properties, which are necessary to diabetic bone healing. However, the noticeable drawbacks of SIS such as fast degradation rate, slow gelling time, and weak mechanical property seriously impede the 3D printing of SIS for bone repair. Method: In this study, we developed a novel kind of 3D-printed scaffold composed of alginate, nano-hydroxyapatite, and SIS. The morphological characterization, biocompatibility, and in vitro biological effects of the scaffolds were evaluated, and an established diabetic rat model was used for testing the in vivo biological effect of the scaffold after implantation. Results: The in vitro and in vivo results show that the addition of SIS can tune the immunomodulatory properties and angiogenic and osteogenic performances of 3D-printed scaffold, where the macrophages polarization of M2 phenotype, migration and tube formation of HUVECs, as well as osteogenic expression of ALP, are all improved, which bode well with the functional requirements for treating diabetic bone nonunion. Furthermore, the incorporation of alginate substantially improves the printability of composites with tunable degradation properties, thereby broadening the application prospect of SIS-based materials in the field of tissue engineering. Conclusion: The fabricated 3D-printed Alg/HA/SIS scaffold provides desirable immunomodulatory effect, as well as good osteogenic and angiogenic performances in vitro and in vivo, which properties are well-suited with the requirement for treating diabetic bone defects. Translational potential of this article: The incorporation of SIS and alginate acid not only provides good printability of the newly fabricated 3D-printed Alg/HA/SIS scaffold, but also improves its immunoregulatory and angiogenic properties, which suits well with the requirement for treating diabetic bone disease and opens up new horizons for the development of implants associating diabetic bone healings.

Recent advancements in tissue engineering offer promising solutions for the repair and reconstruction of the urinary system, particularly in cases of urinary organ injuries. Historically, autologous tissue grafts and allografts have been the primary options for repairing damaged tissues. However, these approaches often lead to complications such as immune rejection, donor site morbidity, and functional limitations. Tissue engineering provides a more sustainable alternative by leveraging the potential of cells, bioactive scaffolds, and growth factors to regenerate and repair damaged tissues. This approach aims not only to restore tissue structure but also to enhance functional recovery. Key challenges in the field include achieving adequate vascularization, overcoming immune responses, and ensuring long-term tissue integration. Recent innovations, such as 3D bioprinting, stem cell-based therapies, and the development of novel biomaterials, show great promise in addressing these challenges. This review explores the current state of tissue engineering applications in the urological system, focusing on the regeneration of the bladder, urethra, and kidneys. We discuss recent breakthroughs, ongoing clinical trials, and emerging technologies, as well as the potential for these approaches to improve clinical outcomes. Finally, we outline critical future directions of tissue engineering in urology, emphasizing the need for interdisciplinary collaboration to overcome existing barriers and accelerate clinical translation.

IntroductionThe occurrence of pachyonychia congenita (PC) and acne inversa (AI) may be related to gene mutations. The aim of this study is to identify the genetic cause in a patient with PC and AI, and to explore the possible molecular mechanism of their co-occurrence.MethodsThe clinical data of the proband were collected, and the genomic DNA of the proband and unaffected parents were extracted. The variant sites of the proband were identified by whole-exome sequencing, and then the variant sites of the proband and his parents were verified by Sanger sequencing.ResultsA heterozygous variant in KRT17 gene was found in the patient, resulting in a missense amino acid variant (p.N92D). The variant was not found in his parents or 100 unrelated healthy controls. In addition, this variant was not found in the gnomad v4 database. The three-dimensional structure analysis of the protein suggested that the polarity of amino acids changed after the variant. After lentiviral plasmid transfection into HaCaT cells, the expression level of NOTCH signaling decreased in the constructed c.274A>G (p.Asn92Asp) of KRT-17 mutant cells compared to that in the wild-type. Subsequent verification confirmed that differences in the expression levels of p-PI3K, AKT and p-AKT between the groups were not statistically significant.DiscussionAlthough this variant has been reported previously, our findings could expand the spectrum of co-occurrence of PC and AI with KRT17 gene variants, and elucidated the possible pathogenesis at the protein level, thereby laying a foundation for the genetic diagnosis and genetic counseling provided to individuals with PC.

Realgar-Indigo Naturalis Formula (RIF) is an oral form of arsenic that is effective against acute promyelocytic leukemia (APL). This multicenter, randomized, controlled trial compared the efficacy of all-trans retinoic acid (ATRA) plus RIF with ATRA plus arsenic trioxide (ATO) in a simplified regimen for non-high-risk APL. Following induction therapy with ATRA and ATO, participants were randomly assigned to receive either ATRA plus ATO or ATRA plus RIF both in a 2-week on 2-week off schedule for consolidation therapy. Once achieving molecular complete remission, the regimen was administered for a total of 6 cycles. All of 108 eligible patients achieved hematological complete remission after induction therapy. The median follow-up time was 29 months. The primary endpoint of two-year disease-free survival was 97% in the ATRA-RIF arm and 98% in the ATRA-ATO arm, respectively. (The ATRA-RIF arm was found to be non-inferior to the ATRA-ATO arm, (P < .01), with a percentage difference of -1% (95%CI, -4.8 to 6.9). No deaths have been observed. Most adverse events were moderate. This study confirms the noninferiority of RIF to ATO for non-high-risk APL, while also offering a more favorable regimen schedule for post-remission therapy. (ClinicalTrials gov. Identifier: as NCT02899169).

The main purpose of this paper is to optimize the drying process and gain a fundamental understanding of the movement of different phases during the drying process of cigarette flakes. Therefore, the drying model of a multiphase porous medium for cigarette flakes has been established in this paper. Binary diffusion of water vapor and gas pressure transport, as well as capillary diffusion of liquid water and gas pressure transport, are considered in this model. The non-equilibrium equations are used to calculate the evaporation rate, and the fluxes of water vapor and liquid water are also obtained. The results indicated that the stochastic stacking model is suitable for studying cigarette flake drying. Because water evaporation absorbs more heat than hot air, the temperature of the cigarette flakes decreases during the drying process. The water activity, vapor density, and vapor mole fraction of the medium layer of cigarette flakes were significantly higher than those of the upper and lower layers. The highest water vapor and liquid water fluxes occur in the medium of the drying process. Additionally, it was observed that the saturated vapor pressure was higher than the equilibrium vapor pressure and steam pressure, non-equilibrium evaporation occurs in the medium of drying. The correlation between the evaporation rate and the drying temperature and humidity of the cigarette flakes was found to be positive.

Abstract Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.

Stellera chamaejasme, a toxic invasive species widespread in degraded alpine grasslands, Qinghai Province, causes a significant threat to the local ecological balance. Accurate monitoring of the leaf chlorophyll content is essential for preventing its expansion over large areas. This study presents an optimal approach by integrating hierarchical dimensionality reduction, stacking ensemble learning, and 1D-CNN models to estimate leaf chlorophyll content in S. chamaejasme using hyperspectral reflectance data. Field spectrometry analysis demonstrates that the combination of Pearson correlation, first derivative, and SPA algorithms can efficiently select the most chlorophyll-sensitive wavelengths, red-edge parameters, and spectral indices related to S. chamaejasme leaves. The stacking ensemble model outperforms the 1D-CNN model in predicting leaf chlorophyll content of S. chamaejasme over the whole growth stage, while the 1D-CNN excels at prediction in each individual growth stage. Comparatively, the 1D-CNN model achieved higher accuracy (R2 > 0.5) in all five growth stages, with optimal performance during the flower bud stage (R2 = 0.787, RMSE = 2.476). This study underscores the potential of combining feature spectra selection with machine learning and deep learning models to monitor S. chamaejasme growth, offering valuable insights for invasive species control and ecological management.

Summary: Universal coatings with versatile surface adhesion, good mechanochemical robustness, and the capacity for secondary modification are of great scientific interest. However, incorporating these advantages into a system is still a great challenge. Here, we report a series of catechol-decorated polyallylamines (CPAs), denoted as pseudo-Mytilus edulis foot protein 5 (pseudo-Mefp-5), that mimic not only the catechol and amine groups but also the backbone of Mefp-5. CPAs can fabricate highly adhesive, robust, multifunctional polyCPA (PCPA) coatings based on synergetic catechol-polyamine chemistry as universal building blocks. Due to the interpenetrating entangled network architectures, these coatings exhibit high chemical robustness against harsh conditions (HCl, pH 1; NaOH, pH 14; H2O2, 30%), good mechanical robustness, and wear resistance. In addition, PCPA coatings provide abundant grafting sites, enabling the fabrication of various functional surfaces through secondary modification. Furthermore, the versatility, multifaceted robustness, and scalability of PCPA coatings indicate their great potential for surface engineering, especially for withstanding harsh conditions in multipurpose biomedical applications.

Hydrogen is considered the optimal solution for achieving high efficiency and low emissions in Wankel rotary engines (WREs). This paper aims to reveal the effect of ignition patterns on the combustion process of a hydrogen-fueled WRE. The results show that the combustion rate of the trailing spark plug (TSP), due to its structural similarity with the passive precombustion chamber, surpasses that of the leading spark plug (LSP). The unidirectional flow field promotes the forward development of the flame of TSP but inhibits the backward development of the flame of LSP. Moreover, the recess in combustion chamber facilitates flame propagation of TSP. Asynchronous ignition mode exhibits a higher indicated thermal efficiency (ITE) than synchronous ignition mode, facilitating effective control of the combustion phase. When the ignition timing of LSP is delayed, and TSP is earlier, the flame of TSP exceeds LSP, resulting in unchanged ITE. When the ignition timing of TSP is delayed, and LSP is earlier, the peak of free radicals and burned volume rate are the highest, resulting in a faster combustion rate. It is recommended that the LSP ignition timing is set earlier for practical operations.

Bone-related diseases refer to a group of skeletal disorders that are characterized by bone and cartilage destruction. Conventional approaches can regulate bone homeostasis to a certain extent. However, these therapies are still associated with some undesirable problems. Fortunately, recent advances in nanomaterials have provided unprecedented opportunities for diagnosis and therapy of bone-related diseases. This review provides a comprehensive and up-to-date overview of current advanced theranostic nanomaterials in bone-related diseases. First, the potential utility of nanomaterials for biological imaging and biomarker detection is illustrated. Second, nanomaterials serve as therapeutic delivery platforms with special functions for bone homeostasis regulation and cellular modulation are highlighted. Finally, perspectives in this field are offered, including current key bottlenecks and future directions, which may be helpful for exploiting nanomaterials with novel properties and unique functions. This review will provide scientific guidance to enhance the development of advanced nanomaterials for the diagnosis and therapy of bone-related diseases.

This research presents a novel port parametric modeling technique using three-dimensional computational fluid dynamics for the design and optimization of intake and exhaust phases in side-ported Wankel rotary engines (WREs). Definitions for the port phases encompass parameters such as port start opening, port full opening, port start closing, and port full closing timings. The four port phase control arcs are obtained by translating and rotating the rotor flank to satisfy the high control accuracy. Further, the shape of the port is further smoothed and varied by four auxiliary circular arcs. Moreover, the influence of port full closing timing and the size of auxiliary circular arcs (R1, and R3) on the intake characteristics is studied.The results show that the novel method can flexibly and effectively control the phases and shapes. The early port full closing timing reduces fluid backflow and improves volumetric efficiency (VE) but increases intake loss (IL). The small size of R1 facilitates to increase the VE and reduce IL. A larger or smaller size of R3 is not conducive to reducing IL, and the smaller size of R3 improves the VE. The novel generation method proposed in this paper provides a theoretical basis to optimize the design of various sizes of side-ported WREs and guidance for practical manufacturing.

Stellera chamaejasme is highly invasive and causes a significant threat to alpine grassland on the Qinghai-Tibet Plateau. It is important to determine its distribution pattern in order to stem the rapid invasion of this toxic weed. In the present study, strategies for mapping S. chamaejasme based on UAV Resonon hyperspectral imaging were assessed in combination with dimension reduction, clustering and ordination analysis, and spectral separability measurement. Field spectrometry analysis showed that the hierarchical procedure of Kruskal-Wallis test and Dunn’s post hoc test, CART and JM distance can efficiently select the minimum optimal wavelengths for S. chamaejasme discrimination and considerably reduce the dimensions of hyperspectral imagery. DCA and RDA ordination revealed that S. chamaejasme identification at the species level is difficult even using hyperspectral feature bands. The reaggregating of TWINSPAN ecological communities based on the criterion of JM distance > 1.9 can result in spectrally delineated S. chamaejasme communities and the co-existing species community. Applying three algorithms of MLC, RF, and SVM, the performance of S. chamaejasme classification based on JM-TWINSPAN schemes was significantly improved compared to that based on TWINSPAN schemes. Of these, RF and JM-TWINSPAN achieved the best classification result (OA = 91.00%, Kappa = 0.83, AD = 14.0%, and QD = 1.2%). The result indicates that the promising accuracy can be achieved in accurate mapping of S. chamaejasme by a multivariate approach, which combines ecological analysis and separability measurement with image classification.

Based on the traditional Chinese cultural belief of “male breadwinner, female homemaker”, as well as the systemic and interactive characteristics of families, this study aims to explore the relationship between maternal gatekeeping behavior and the quality and quantity of paternal parenting, as well as adolescent aggressive behavior. A total of 483 seventh-grade students completed questionnaires on maternal gatekeeping behavior, paternal involvement, parenting styles, and aggressive behavior. Latent profile analysis identified four parenting combinations: positive, negative, mixed, and neglectful. Adolescents under negative parenting exhibited the highest aggression and experienced the highest maternal gatekeeping behavior, while those under positive and neglectful parenting showed the least aggression and least maternal gatekeeping behavior. Maternal gatekeeping behavior correlated with paternal negative parenting and adolescent aggression. Paternal negative parenting mediated the relationship between maternal gatekeeping and aggression, while paternal involvement moderated this relationship. These findings highlight the role of parental interaction in adolescent behavior and support family-based interventions.

The multivalency of bioligands in living systems brings inspiration for not only the discovery of biological mechanisms but also the design of extracellular matrix (ECM)-mimicking biomaterials. However, designing controllable multivalency construction strategies is still challenging. Herein, we synthesized a series of well-defined multivalent antimicrobial peptide polymers (mAMPs) by clicking ligand molecules onto polymers prepared by reversible addition-fragmentation chain transfer polymerization. The multiple cationic ligands in the mAMPs could enhance the local disturbance of the anionic phospholipid layer of the bacterial membrane through multivalent binding, leading to amplification of the bactericidal effect. In addition to multivalency-enhanced antibacterial activity, mAMPs also enable multivalency-assisted hydrogel fabrication with an ECM-like dynamic structure. The resultant hydrogel with self-healing and injectable properties could be successfully employed as an antibacterial biomaterial scaffold to treat infected skin wounds. The multivalency construction strategy presented in this work provides new ideas for the biomimetic design of highly active and dynamic biomaterials for tissue repair and regeneration.

Polyetheretherketone (PEEK) is deemed to be a promising alternative to biomedical metals for orthopedic and dental implantation attributed to its bone-like elastic modulus and good biocompatibility. Nevertheless, the bioinert PEEK elicits an acute and irreducible inflammatory immune response after implantation, resulting in fibrous encapsulation and ultimately inferior osseointegration. Therefore, endowing the PEEK surface with immunomodulatory function is essential for advanced osseointegration. Herein, surface bisphosphonation of PEEK is achieved by using mussel-inspired chemistry together with alendronate, which can not only mitigate the early servious inflammatory immune response by promoting macrophages polarization toward the pro-healing M2 phenotype, but also construct a favorable osteoimmune microenvironment to promote the angiogenesis of human umbilical vein endothelial cells (HUVECs) and the osteogenesis of MC3T3-E1 osteoblasts. In vivo evaluation reveals an ameliorative osseointegration of PEEK implant after surface bisphosphonation, confirming the in vitro results. Our findings elucidate that the PEEK implant after surface bisphosphonation can positively regulate early immune reaction to facilitate subsequent angiogenesis and osteogenesis processes, which is desirable for orthopedic and dental implantation.

Abstract Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body. The molecular mechanisms of OA are currently unknown. OA is a heterogeneous disease that affects the entire joint, and multiple tissues are altered during OA development. To better understand the pathological mechanisms of OA, new approaches, methods, and techniques need to be used to understand OA pathogenesis. In this review, we first focus on the epigenetic regulation of OA, with a particular focus on DNA methylation, histone modification, and microRNA regulation, followed by a summary of several key mediators in OA-associated pain. We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain, such as CRISPR, scRNA sequencing, and lineage tracing. Next, we discuss the timely updates concerning cell death regulation in OA pathology, including pyroptosis, ferroptosis, and autophagy, as well as their individual roles in OA and potential molecular targets in treating OA. Finally, our review highlights new directions on the role of the synovial lymphatic system in OA. An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

Skeletal diseases normally represents a grievous imbalance between osteoblasts for bone formation and osteoclasts for bone resorption. A lack of osteogenic function can make it difficult to repair pathological bone erosion. Therefore, substantial efforts have been made to remedy these issues, with the aid of bioactive molecules, herbs and materials. Following recent insights, the importance of epigenetic gene regulation is increasingly evident, especially microRNAs. MicroRNAs can silence target genes by inhibiting mRNA translation or degrading mRNA molecules by binding to their 3′-untranslated region. There is accumulating evidence indicating that the miRNAs significantly involved in osteogenic gene expression, signaling pathway intervention and programmed cell death. Besides, numerous new target drugs (microRNA inhibitors or agonists) have been proposed to exploit its value in skeletal physiology and pathology. In this review, we mainly discuss the role of microRNAs in the context of skeletal disease-associated osteoblast differentiation, the applications of microRNA polymorphisms as biomarkers for diagnostic and therapeutic targets, and the challenges to meet this goal. Our summary provides novel horizon for improving the therapeutic effect of microRNAs, which may be beneficial to the further clinical translation of microRNAs in the treatments of skeletal diseases.

Polyetheretherketone (PEEK) is a desirable alternative to conventional biomedical metals for orthopedic implants due to the excellent mechanical properties. However, the inherent bioinertness of PEEK contributes to inferior osseointegration of PEEK implants, especially under pathological conditions of osteoporosis. Herein, a programmed surface is designed and fabricated on PEEK to dictate osteoimmunomodulation and bone regeneration sequentially. A degradable hybrid coating consisting of poly(lactide-co-glycolide) and alendronate (ALN) loaded nano-hydroxyapatite is deposited on PEEK and then interleukin-4 (IL-4) is grafted onto the outer surface of the hybrid coating with the aid of N2 plasma immersion ion implantation and subsequent immersion in IL-4 solution. Dominant release of IL-4 together with ALN and Ca2+ during the first few days synergistically mitigates the early acute inflammatory reactions and creates an osteoimmunomodulatory microenvironment that facilitates bone regeneration. Afterwards, slow and sustained delivery of ALN and Ca2+ in the following weeks boosts osteogenesis and suppresses osteoclastogenesis simultaneously, consequently ameliorating bone-implant osseointegration even under osteoporotic conditions. By taking into account the different phases in bone repair, this strategy of constructing advanced bone implants with sequential functions provides customizable and clinically viable therapy to osteoporotic patients.

Summary Preclinical studies have shown that the induction of secretory IgA (sIgA) in mucosa and neutralizing antibodies (NAbs) in sera is essential for designing vaccines that can effectively block the transmission of HIV‐1. We previously showed that a vaccine consisting of bacterium‐like particles (BLPs) displaying Protan‐gp120AE‐MTQ (PAM) could induce mucosal immune responses through intranasal (IN) immunization in mice and NAbs through intramuscular (IM) immunization in guinea pigs. Here, we evaluated the ability of this vaccine BLP‐PAM to elicit HIV‐1‐specific mucosal and systemic immune responses through IN and IM immunization combination strategies in rhesus macaques. First, the morphology, antigenicity and epitope accessibility of the vaccine were analysed by transmission electron microscopy, bio‐layer interferometry and ELISA. In BLP‐PAM‐immunized macaques, HIV‐1‐specific sIgA were rapidly induced through IN immunization in situ and distant mucosal sites, although the immune responses are relatively weak. Furthermore, the HIV‐1‐specific IgG and IgA antibody levels in mucosal secretions were enhanced and maintained, while production of serum NAbs against heterologous HIV‐1 tier 1 and 2 pseudoviruses was elicited after IM boost. Additionally, situ mucosal responses and systemic T cell immune responses were improved by rAd2‐gp120AE boost immunization via the IN and IM routes. These results suggested that BLP‐based delivery in combination with the IN and IM immunization approach represents a potential vaccine strategy against HIV‐1.

Abstract Periprosthetic osteolysis (PPO) triggered by wear particles is the most severe complication of total joint replacement (TJR) surgeries, representing the major cause of implant failure, which is public health concern worldwide. Previous studies have confirmed the specialized role of osteoclast-induced progressive bone destruction in the progression of PPO. Additionally, the reactive oxygen species (ROS) induced by wear particles can promote excessive osteoclastogenesis and bone resorption. Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), a cellular enzyme, is considered to be responsible for the production of ROS and the formation of mature osteoclasts. However, NOX4 involvement in PPO has not yet been elucidated. Therefore, we investigated the mechanism by which NOX4 regulates osteoclast differentiation and the therapeutic effects on titanium nanoparticle-induced bone destruction. We found that NOX4 blockade suppressed osteoclastogenesis and enhanced the scavenging of intracellular ROS. Our rescue experiment revealed that nuclear factor-erythroid 2-related factor 2 (Nrf2) silencing reversed the effects of NOX4 blockade on ROS production and osteoclast differentiation. In addition, we found increased expression levels of NOX4 in PPO tissues, while NOX4 inhibition in vivo exerted protective effects on titanium nanoparticle-induced osteolysis through antiosteoclastic and antioxidant effects. Collectively, these findings suggested that NOX4 blockade suppresses titanium nanoparticle-induced bone destruction via activation of the Nrf2 signaling pathway and that NOX4 blockade may be an attractive therapeutic approach for preventing PPO. Graphical Abstract

ObjectiveDiagnosis classification and risk stratification are crucial in the prognosis prediction and treatment selection of acute myeloid leukemia (AML). Here, we used a database of 536 AML patients to compare the 4th and 5th WHO classifications and the 2017 and 2022 versions of ELN guidance.MethodsAML patients were classified according to the 4th and 5th WHO classifications, as well as the 2017 and 2022 versions of the European LeukemiaNet (ELN) guidance. Kaplan–Meier curves with log-rank tests were used for survival analysis.ResultsThe biggest change was that 25 (5.2%), 8 (1.6%), and 1 (0.2%) patients in the AML, not otherwise specified (NOS) group according to the 4th WHO classification, were re-classified into the AML-MR (myelodysplasia-related), KMT2A rearrangement, and NUP98 rearrangement subgroups based on the 5th WHO classification. Referring to the ELN guidance, 16 patients in the favorable group, six patients in the adverse group, and 13 patients in the intermediate group based on the 2017 ELN guidance were re-classified to the intermediate and adverse groups based on the 2022 ELN guidance. Regrettably, the Kaplan–Meier curves showed that the survival of intermediate and adverse groups could not be distinguished well according to either the 2017 or 2022 ELN guidance. To this end, we constructed a risk model for Chinese AML patients, in which the clinical information (age and gender), gene mutations (NPM1, RUNX1, SH2B3, and TP53), and fusions (CBFB::MYH11 and RUNX1::RUNX1T1) were included, and our model could help divide the patients into favorable, intermediate, and adverse groups.ConclusionThese results affirmed the clinical value of both WHO and ELN, but a more suitable prognosis model should be established in Chinese cohorts, such as the models we proposed.

The widespread adoption of hybrid rice varieties in China is a successful example, showing the role of agricultural technology in terms of food security. However, the dynamic diffusion of hybrid rice varieties and their effect on rice production requires further study. Based on data on hybrid rice adoption at the provincial level from 1984 to 2011, we applied the Ordinary Least Squares (OLS) and Geographically and Temporally Weighted Regression (GTWR) models to investigate the spatial and temporal effects of hybrid rice adoption at national and provincial levels. Overall, the effects of hybrid rice adoption on rice production have decreased over time. However, the results showed possible spillover and crowding effects of hybrid rice adoption across provinces. In particular, the development of hybrid rice varieties in Hunan province has had a significant influence on changes in rice yield and the distribution of rice areas in other regions. This study, therefore, serves as a reference in understanding the dynamic distribution of high-yield rice variety adoption in relation to food security and for designing appropriate agricultural extension strategies. However, further research is needed to identify the determinants affecting changes in rice farming in complex environments and associated ecological systems.

Inflammatory responses of nucleus pulposus (NP) can induce imbalanced anabolism and catabolism of extracellular matrix, and the cytosolic dsDNA accumulation and STING–NF–κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc (IVD) degeneration. Herein, we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid (HA-CHO) and poly(amidoamine) PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment, where the formation of dynamic Schiff base bonds in the system (siSTING@HPgel) was able to overcome the shortcomings such as low cellular uptake, short half-life, and rapid degradation of siRNA-based strategy. PAMAM not only formed complexes with siRNA to promote siRNA transfection, but also served as dynamic crosslinker to construct hydrogel, and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells. Finally, the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model, revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.

Polyetheretherketone (PEEK) has been widely used as orthopedic and dental materials due to excellent mechanical and physicochemical tolerance. However, its biological inertness, poor osteoinduction, and weak antibacterial activity make the clinical applications in a dilemma. Inspired by the mussel adhesion mechanism, here we reported a biomimetic surface strategy for rational integration and optimization of anti-infectivity and osteo-inductivity onto PEEK surfaces using a mussel foot proteins (Mfps)-mimic peptide with clickable azido terminal. The peptide enables mussel-like adhesion on PEEK biomaterial surfaces, leaving azido groups for the further steps of biofunctionalizations. In this study, antimicrobial peptide (AMP) and osteogenic growth peptide (OGP) were bioorthogonally clicked on the azido-modified PEEK biomaterials to obtain a dual-effect of host defense and tissue repair. Since bioorthogonal clicking allows precise collocation between AMP and OGP through changing their feeding molar ratios, an optimal PEEK surface was finally obtained in this research, which could long-term inhibit bacterial growth, stabilize bone homeostasis and facilitate interfacial bone regeneration. In a word, this upgraded mussel surface strategy proposed in this study is promising for the surface bioengineering of inert medical implants, in particular, achieving rational integration of multiple biofunctions to match clinical requirements.

Mesenchymal stem cells (MSCs), with high self-renewal ability and multipotency, are commonly used as the seed cells for tissue engineering. However, the reduction and loss of multipotential ability after necessary expansion in vitro set up a heavy obstacle to the clinical application of MSCs. Here in this study, we exploit the autologous crystallization ability of biocompatible poly (ε-caprolactone) (PCL) to obtain uniformly distributed nanoneedle arrays. By controlling the molecular weight of PCL, nanoneedle with a width of 2 μm and height of 50 nm, 80 nm, and 100 nm can be successfully fabricated. After surface chemical modification with polydopamine (PDA), the water contact angle of the fabricated PCL nanoneedle arrays are reduced from 84° to almost 60° with no significant change of the nanostructure. All the fabricated substrates are cultured with bone marrow MSCs (BMMSCs), and the adhesion, spreading, proliferation ability and multipotency of cells on different substrates are investigated. Compared with the BMMSCs cultured on pure PCL nanoneedle arrays, the decoration of PDA can improve the adhesion and spreading of cells and further change them from aggregated distribution to laminar distribution. Nevertheless, the laminar distribution of cultured cells leads to a weak cell-cell interaction, and hence the multipotency of BMMSCs cultured on the PCL-PDA substrates is decimated. On the contrary, the pure PCL nanoneedle arrays can be used to maintain the multipotency of BMMSCs via clustered growth, and the PCL1 nanoneedle array with a height of 50 nm is more promising than the other 2 with regard to the highest proliferation rate and best multipotential differentiation ability of cultured cells. Interestingly, there is a positive correlation between the strength of cell-cell interaction and the multipotency of stem cells in vitro. In conclusion, we have successfully maintained the multipotency of BMMSCs by using the PCL nanoneedle arrays, especially the PCL1 nanoneedle array with a height of 50 nm, as the substrates for in vitro extension, and further revealed the importance of cell-cell interaction on the multipotency of MSCs. The study provides a theoretical basis for the behavioral regulation of MSCs, and is instructive to the design of tissue engineering scaffolds.

The repair of critical-sized bone defects (CSBD) remains a significant challenge in clinical practice. Personalized 3D porous scaffolding is generally considered an ideal approach for directed regeneration of CSBD, which usually has irregular and complex 3D geometry. In this study, we designed a customized porous scaffold rabbit radius based on a body-centered cubic unit. Borate bioactive glass/polycaprolactone (BBG/PCL) composite scaffolds with different BBG contents (0%, 5%, 10%, 20%, and 40%) were fabricated using selective laser sintering. The pore geometry, porosity, mechanical strength, hydrophilicity, protein absorption, degradation behavior, in vitro cytocompatibility, and osteogenesis differentiation of the composite scaffolds were systematically characterized. The in vivo biological properties of the BBG/PCL composite scaffold for CSBD repair were assessed using a rabbit foreleg radius defect model. The results indicate that the BBG/PCL composite scaffold with 20% BBG content effectively promoted the proliferation of osteoblasts and repaired the rabbit radius defects. The mechanical strength of the scaffold was sufficient to maintain the integrity of the scaffold structure during a relatively long CSBD repair. Our results indicate that the BBG/PCL composite scaffold can be anticipated to be a promising biomaterial for CSBD repair.

The power generated by flexible wearable devices (FWDs) is normally insufficient to eradicate bacteria, and many conventional antibacterial strategies are also not suitable for flexible and wearable applications because of the strict mechanical and electrical requirements. Here, polypyrrole (PPy), a conductive polymer with a high mass density, is used to form a nanostructured surface on FWDs for antibacterial purposes. The conductive films with PPy nanorods (PNRs) are found to sterilize 98.2 ± 1.6% of Staphylococcus aureus and 99.6 ± 0.2% of Escherichia coli upon mild electrification (1 V). Bacteria killing stems from membrane stress produced by the PNRs and membrane depolarization caused by electrical neutralization. Additionally, the PNR films exhibit excellent biosafety and electrical stability. The results represent pioneering work in fabricating antibacterial components for FWDs by comprehensively taking into consideration the required conductivity, mechanical properties, and biosafety.

Biobased poly(γ-methyl-α-methylene-γ-butyrolactone) (PMMBL) has attracted interest because it is biorenewable and exhibits superior properties to petroleum-based linear analog poly(methyl methacrylate) (PMMA). Here the authors report the synthesis of well-defined PMMBL-based ABA tri-block copolymers, enabled by dual-initiating and living frustrated Lewis pairs, which have superior mechanical properties compared to those of PMMA-based tri-BCPs.

A 50-year-old female patient presented with post-exercise dyspnea in September 2016, and was subsequently diagnosed with SCLC with multiple brain and spinal metastases. The first-line treatment was etoposide combined with cisplatin and synchronously performed radiotherapy for the brain and spinal cord metastases. She was treated with anlotinib after disease progression in December 2018 and continued to have clinical benefit for nearly 25 months. Unexpectedly, the patient can still benefit from further combination treatment with durvalumab after another disease progression in February 2021. Thus, it may be a potential option to use anlotinib along with immunotherapy after the anlotinib resistance in SCLC, but more clinical data are still needed to confirm it. Moreover, ctDNA dynamic monitoring was performed and reflected the outcome of the process of treatment.

Poor osseointegration ability and the release of worn debris after implantation are the main issues impeding the clinic application of polyether ether ketone (PEEK) as orthopedics. To address these problems, we expect that the initial deposition of diamond-like carbon (DLC) coating on PEEK substrate and the subsequent introduction of amino groups onto sample surface using plasma immersion ion implantation (PIII) have the potential to simultaneously improve the mechanical performance and osseointegration. On one hand, the surface hardness is raised from 0.38 ​GPa to 2.99 ​GPa and the elastic modulus reaches 35 ​GPa after DLC deposition, while no failure is observed in the scratch tests even the loading force is up to 100 ​N. On the other hand, the introduced amino groups facilitate the adhesion, proliferation, and osteogenic differentiation of the osteoblasts in vitro, and further enhanced the peri-implant bone regeneration in vivo. With the merits of low cost, clean approach, and ease of operation, the approach described here holds great potential for biomedical applications.

Abstract Background The relationship between kidney function and hearing loss has long been recognized, but evidence of this association mostly comes from small observational studies or other populations. The aim of this study is to explore the association between reduced kidney function and hearing loss in a large population-based study among the middle-aged and elderly Chinese. Methods Data collected from the Chinese Health and Retirement Longitudinal Study (CHARLS) in 2015 were used for analysis. A cross-sectional study was conducted among 12,508 participants aged 45 years and older. Hearing loss, the outcome of this study, was defined according to interviewees’ responses to three survey questions related to hearing in the CHARLS. Estimated glomerular filtration rate (eGFR) was employed to assess kidney function, and participants were classified into three categories based on eGFR: ≥90, 60–89 and

Topographical cues on material surfaces are crucial for guiding the behavior of nerve cells and facilitating the repair of peripheral nerve defects. Previously, micron-grooved surfaces have shown great potential in controlling nerve cell alignment for studying the behavior and functions of those cells and peripheral nerve regeneration. However, the effects of smaller-sized topographical cues, such as those in the submicron- and nano-scales, on Schwann cell behavior remain poorly understood. In this study, four different submicron-grooved polystyrene films (800/400, 800/100, 400/400, and 400/100) were fabricated to study the behavior, gene expression, and membrane potential of Schwann cells. The results showed that all submicron-grooved films could guide the cell alignment and cytoskeleton in a groove depth-dependent manner. Cell proliferation and cell cycle assays revealed that there was no significant difference between the submicron groove samples and the flat control. However, the submicron grooves can direct the migration of cells and upregulate the expression of critical genes in axon regeneration and myelination (e.g., MBP and Smad6). Finally, the membrane potential of the Schwann cells was significantly altered on the grooved sample. In conclusion, this study sheds light on the role of submicron-grooved patterns in regulating the behavior and function of Schwann cells, which provides unique insights for the development of implants for peripheral nerve regeneration.

Stellera chamaejasme (Thymelaeaceae) is amongst the worst invasive species of the alpine grasslands on the Qinghai–Tibet Plateau; timely and effective monitoring is critical for its prevention and control. In this study, by using high spatial resolution Planet imagery, an optimal approach was explored to improve the discrimination of S. chamaejasme from surrounding communities, integrated with TWINSAPN technique, Transformed divergence and image classification algorithms. Results demonstrated that there were obvious spectral conflicts observed among the TWINSPAN ecological communities, owing to the inconsistency of S. chamaejasme coverage within the communities. By determining the threshold of spectral separability, the adjustment of ecological classification produced spectrally separated S. chamaejasme communities and native species communities. The sensitive index characterizing the spectra of S. chamaejasme contributes to its discrimination; moderate or good classification accuracy was obtained by using four machine learning algorithms, of which Random Forest achieved the highest accuracy of S. chamaejasme classification. Our study suggests the distinct phenological feature of S. chamaejasme provides a basis for the detection of the toxic weed, and the establishment of communities using the rule of spectral similarity can assist the accurate discrimination of invasive species.

Integration of two or more biomolecules with synergetic and complementary effects on a material surface can help to obtain multi-functions for various biomedical applications. However, the amounts of biomolecules integrated and their physiological functions are compromised due to the limited surface anchoring sites. Herein, we propose a novel concept of film engineering strategy “from surface to bulk synergetic modification”. This new concept is realized by employing the surface amine groups of plasma polymerized allylamine (PPAm) film for grafting a molecule e.g., thrombin inhibitor, bivalirudin (BVLD), meanwhile its bulk amine groups is used as a universal depot for storing and releasing therapeutic nitric oxide (NO) gas as supplement to the functions of BVLD. It is demonstrated that such a “from surface to bulk synergetic modification” film engineering can impart the modified-substrates with anti-platelet and anti-coagulant dual functions, giving rise to a highly endothelium-mimetic thromboresistant property. We believe that our research provides a very promising strategy to deliver multifunctional surface versatilely that require NO release in combination with other properties, which will find broad biomedical applications in blood-contacting devices, and et al. Moreover, it also provides a brand-new film engineering strategy for tailoring surface multi-functionalities of a wide range of materials. Keywords: Surface chemistry, Amine-bearing coating, Synergic modification, Biomolecule grafting, Nitric oxide loading

Abstract Background Acute promyelocytic leukemia (APL) is a highly curable disease when treated with all-trans retinoid acid (ATRA) and arsenic trioxide (ATO). The combination of ATO and ATRA has become the standard therapeutic protocol for induction therapy in non-high-risk APL. An oral arsenic realgar-indigo naturalis formula (RIF) has also showed high efficacy and it has a more convenient route of administration than the standard intravenous regimen. Unlike in previous trials, the arsenical agent was used simultaneously with ATRA during post-remission therapy in this trial. Methods This study was designed as a multicenter, randomized controlled trial. The trial has a non-inferiority design with superiority being explored if non-inferiority is identified. All patients receive ATRA-ATO during the induction therapy. After achieving hematologic complete remission (HCR), patients were randomly assigned (1:1) to receive treatment with ATRA-RIF (experimental group) or ATRA-ATO (control group) as the consolidation therapy. During the consolidation therapy, the two groups receive ATRA plus RIF or intravenous ATO 2 weeks on and 2 to ~ 4 weeks off until molecular complete remission (MCR), then ATRA and oral RIF 2 weeks on and 2 to ~ 4 weeks off giving a total of six courses. Discussion This trial aims to compare the efficacy of ATRA-ATO versus ATRA-RIF in non-high-risk patients with APL, to demonstrate that oral RIF application reduces the total hospitalization days and medical costs. The simple schedule was studied in this trial. Trial registration ClinicalTrials.gov, NCT02899169. Registered on 14 September 2016.

At present, two-stage centrifugal compressors based on air bearing and high-speed motor technology are widely used in automotive hydrogen fuel cells. The low-pressure stage and high-pressure stage of the compressor are directly connected through an interstage pipeline, thus the structure of the interstage pipeline has an important influence on the aerodynamic performance of the compressor. In this work, a two-stage compressor with three different interstage pipelines were investigated experimentally and numerically. Results show that affected by the interstage pipeline bend section, the flow distortion will be induced at the impeller inlet of the high-pressure stage, and the distortion intensity changes with the pipeline structure. Among the three models, the EPC (elbow pipe change) model induces the most intense total pressure distortion at the condition of 80 kr/min and 130% mass flow rate, resulting in an efficiency reduction of 2 and 1.5 percentage points compared with the SPC (straight pipe change) and the TPC (total pipe change) model, respectively. Further research indicates that the upstream distortion has obvious influence on the downstream rotor blades. As the blade height decreases, the load becomes more uniform on the main blades, while the load extremum migrates to the trailing edge on the splitter blades. Finally, three models are tested, and their performance is compared at three typical rotational speeds., It is recommended that interstage pipelines similar to SPC models should be chosen to improve the two-stage compressor efficiency in the design.

To study the rewetting characteristics of tobacco strips during the redrying stage, a conjugate heat and mass transfer model of tobacco strips was established based on their physical properties. The fundamental relationship between the multiphysical fields and humidity fields of tobacco strips and the key process parameters was considered in this model, and the feasibility of the model was verified via experiments. Based on this model, the transfer and variation laws of the moisture content, humidification rate, and temperature of tobacco strips under different relative humidity and temperature conditions were studied, and the rewetting process parameters of tobacco strips were determined using COMSOL Multiphysics. The results show that this model can be used to study the rewetting characteristics of tobacco strips during the redrying stage. The rewetting of tobacco strips can be divided into two stages, namely, the accelerated stage and approximate constant rate increase stage, where the former stage has a greater impact on the rewetting effect. The higher the relative humidity and temperature, the greater the change in the moisture content, humidification rate, and effective moisture diffusivity, and the faster the increase rate. The best rewetting effect was achieved when the relative humidity was 85% and the temperature was 55 °C. Under these conditions, the moisture content of the tobacco strips was 11% to 13%, the humidification rate was 0.03 %/s to 0.29 %/s, the highest effective moisture diffusivity was 7.8 × 10−10 m2/s, and the maximum activation energy was 37.86 kJ/mol. This study provides a theoretical basis and data support for analyzing the characteristics of the rewetting process and for optimizing the process parameters.

To accurately study the drying characteristics of tobacco strips in the process of redrying, a discrete heaped physical model of tobacco strips is built. Based on this model, a convective drying multiphase porous media model of the heaped tobacco strips is established, which considers the binary diffusion and transport of vapor inside and outside the tobacco leaf. The model is solved using COMSOL Multiphysics, and the accuracy of the model is verified by experiments. The changes in hot air velocity, vapor and moisture content, and evaporation rate in heaped tobacco strips with different thicknesses are analyzed. The results show that: it is feasible to study the drying characteristics of tobacco strips in redrying using a discrete heaped model; there were significant differences in water content, evaporation rate, and temperature in different regions of heaped tobacco strips; the increase in heaping thickness will significantly reduce the uniformity of heat and mass transfer of tobacco strips in the process of convection drying. This model can provide a reference for the study of heat and mass transfer in porous media, such as tobacco strips in the heaping state.

In order to effectively weaken the leakage flow and shock intensity of traditional “swing” type guide vanes in a variable nozzle turbine, a new flow control device named the “split sliding guide vane” (SSGV) is studied in the present work. Steady and unsteady calculations were carried out on both the SSGV and base model at 10%, 40%, and 100% open positions. The shock test was performed to verify the accuracy of the numerical method. The results showed that at 10%, 40%, and 100% open positions, the leakage flow of the SSGV was 43%, 51%, and 40% of that of the base model, respectively. When 10% open, the turbine efficiency increased by 12%, compared with the base model, since the SSGV could effectively inhibit the clearance leakage flow. Due to the increased distance between the rotor and guide vane, the shock intensity of the SSGV was only 52% of that of the base model when 40% was open. The SSGV could reduce the static pressure loss on the guide vane pressure surface, but for the guide vane suction surface, the static pressure distribution appeared in a “W” shape due to the influence of the vane profile. Finally, the flow in the rotor was studied, which showed that the weakening of the shock and reduction of the clearance leakage flow in the guide vane were also beneficial for the strength of downstream rotor blades.

The immune responses are involved in every stage after implantation but the reported immune-regulated materials only work at the beginning without fully considering the different phases of bone healing. Here, poly(aryl-ether-ether-ketone) (PEEK) is coated with a programmed surface, which rapidly releases interleukin-10 (IL-10) in the first week and slowly delivers dexamethasone (DEX) up to 4 weeks. Owing to the synergistic effects of IL-10 and DEX, an aptly weak inflammation is triggered within the first week, followed by significant M2 polarization of macrophages and upregulation of the autophagy-related factors. The suitable immunomodulatory activities pave the way for osteogenesis and the steady release of DEX facilitates bone regeneration thereafter. The sequential immune-mediated process is also validated by an 8-week implementation on a rat model. This is the first attempt to construct implants by taking advantage of both immune-mediated modulation and sequential regulation spanning all bone regeneration phases, which provides insights into the fabrication of advanced biomaterials for tissue engineering and immunological therapeutics.

The mitochondrial membrane potential (MMP, ΔΨmito) provides the charge gradient required for mitochondrial functions and is a key indicator of cellular health. The changes in MMP are closely related to diseases and the monitoring of MMP is thus vital for pathological study and drug development. However, most of the current fluorescent probes for MMP rely solely on the cell fluorescence intensity and are thus restricted by poor photostability, rendering them not suitable for long-term dynamic monitoring of MMP. Herein, an MMP-responsive fluorescent probe pyrrolyl quinolinium (PQ) which is capable of reversible migration between mitochondria and nucleolus is developed and demonstrated for dynamic evaluation of MMP. The fluorescence of PQ translocates from mitochondria to nucleoli when MMP decreases due to the intrinsic RNA-specificity and more importantly, the translocation is reversible. The cytoplasm to nucleolus fluorescence intensity ratio is positively correlated with MMP so that this method avoids the negative influence of photostability and imaging parameters. Various situations of MMP can be monitored in real time even without controls. Additionally, long-term dynamic evaluation of MMP is demonstrated for HeLa cells using PQ in oxidative environment. This study is expected to give impetus to the development of mitochondria-related disease diagnosis and drug screening.

Abstract Background The treatment of acute promyelocytic leukemia (APL) has been revolutionized in the past two decades by the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). It suggests that non-high-risk APL patients can be cured without chemotherapy. However, ATRA plus chemotherapy is still the standard therapy for the high-risk patients. Central nervous system (CNS) relapse remains a significant cause of treatment failure in high-risk patients. However, increasing the ATO concentration in cerebrospinal fluid (CSF) may reduce CNS relapse in high-risk patients. Mannitol can allow ATO to penetrate the blood-brain barrier (BBB) and reach therapeutically effective levels in the CSF. It is used for the treatment of CNS relapse in patients APL. We compare ATRA-ATO with ATRA-ATO plus chemotherapy in both high-risk and non-high-risk patients with APL. Methods This study was designed as a multicenter randomized controlled trial. Patients with APL were randomly assigned into two groups: the ATRA-ATO group (experimental group) and the ATRA-ATO plus chemotherapy group (control group). The experimental group receives therapy with ATRA-ATO for induction, consolidation and maintenance therapy. In the high-risk patients, mannitol will be used with ATO in the consolidation and maintenance therapy. Hydroxyurea will be used in patients who developed leukocytosis in the induction therapy. The control group receives therapy with ATRA-ATO plus chemotherapy for induction and consolidation therapy. Discussion In this study, a randomized clinical trial design is described. It aims to compare the efficacy of ATRA-ATO versus ATRA-ATO plus chemotherapy in all-risk patients with APL. Trial registration Chinese Clinical Trials Registry, ID: ChiCTR-IPR-15006821. Registered on 27 July 2015.

Bacteria are known to be sensitive to electrical interactions with the environment. Here, the authors report on a study into how the antibacterial properties of carbon-doped titania nanotubes are affected by capacitance after charging with direct and alternating currents.

With increasingly strict emission regulations and growing environmental concerns, it is urgent to improve engine performance and reduce emissions. In this paper, multivariate nonlinear regression (MNLR) combined with multiobjective particle swarm optimization (MOPSO) was implemented to optimize the performance and emissions of a large low-speed two-stroke dual-fuel marine engine. First, a simulation model of a dual-fuel engine was established using AVL-BOOST software. Next, a single-factor scanning value method was applied to control a range of variables, including intake pressure, intake temperature, and natural gas mass fraction. Then, a nonlinear regression model was established using the statistical multivariate nonlinear regression equation. Finally, the multiobjective optimization algorithm implementing MOPSO was used to solve the trade-off between performance and emissions. It was found that when the intake pressure was 3.607 bar, the intake temperature was 297.15 K and the natural gas mass fraction was 0.962. The engine power increased by 0.34%, the brake specific fuel consumption (BSFC) reduced by 0.21%, and the NOx emissions reduced by 39.56%. The results show that the combination of multiple nonlinear regression and intelligent optimization algorithm is an effective method to optimize engine parameter settings.

Overuse of nitrogen fertilizer represents a considerable environmental problem globally, but especially in China. Recently, a recent approach on an experimental scale based on the diffusion of the so-called Three-Control Technology (TCT) successfully alleviated the overuse of nitrogen fertilizer in southern China villages in the Guangdong Province, serving as a reference point for other rice-producing countries tackling similar challenges. Here, we assessed the correlation between rice yields and reduction in the use of nitrogen fertilizer following the introduction of TCT. Our study was based on the collection of primary data from 248 households randomly selected from four rice-growing areas of Guangdong Province, China. Our results show that TCT significantly improved the efficiency in the use of nitrogen. Crucially, participating farmers, including both full adopters and partial adopters, were found to fundamentally change their application practices of nitrogen fertilizer, resulting in major improvements in the local soil and water systems.