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With the development of science over the years, people have increasingly realized the importance of science communication. Unfortunately, very little research has focused on helping medical students develop the capabilities of science communication. To improve medical students' science communication and evaluate the effectiveness of New Media through mobile clients in health science communication, a competition was held among medical undergraduates. Outstanding works were selected for publication on our official health science communication WeChat account. Furthermore, the participants volunteered to complete a questionnaire survey to help us assess students' awareness of science communication. Our analysis revealed that students had a strong willingness to serve society and to participate in science communication work. Students generally agreed that science communication work had excellent effects on professional knowledge and related skills. In addition, the correlation results showed that the greater students' willingness to participate in health science communication was, the greater their sense of gain. New Media effectively expand the influence of students' popular science works. Our findings suggest that competition in science communication has a positive impact on enhancing students' awareness and capabilities in science communication. In addition, New Media are an effective way to improve students' scientific communication efficiency. However, we also noted that students' participation rate and enthusiasm for scientific communication were not high. Further research is needed to determine the reasons for this situation and potential strategies to further improve students' science communication.

Considering the real-world dilemma of leaders' high long-term orientation and employees' insufficient innovative behaviors in practice, this study systematically explored the relationship between leaders' long-term orientation and employees' innovative behaviors using challenge and threat appraisals as the mediating variables and promotion focus as the moderating variable. An empirical analysis was performed on 348 two-stage leader-employee matching questionnaires collected from emerging industries in China. Leaders' long-term orientation was positively related to employees' innovative behaviors overall, and had positive and negative indirect relationships with employees' innovative behaviors via employees' challenge and threat appraisals, respectively. Employees' promotion focus positively moderated the relationship between leaders' long-term orientation and employees' challenge appraisal, negatively moderated the relationship between leaders' long-term orientation and employees' threat appraisals, and further moderated the mediating role of challenge or threat appraisal in the relationship between leaders' long-term orientation and employees' innovative behaviors. This study revealed the relationship between leaders' long-term orientation on employees' innovative behaviors and its boundaries. It expands theoretical research on leaders' long-term orientation and employees' innovative behaviors.

"Research Findings:" Digital leadership as an urgent and emerging topic has attracted public attention, but its nature, definition, and constructs have not been thoroughly explored for the Chinese culture. This study uses a grounded theory approach to examine how Chinese principles are utilized at "Model Level" preschools to define, understand, and practice digital leadership in preschools. Eight principals from "Model Level" preschools in Shanghai were purposefully sampled and interviewed individually. The interview transcripts' inductive coding and interpretive analysis revealed a Chinese definition of digital leadership and its three constructs: Attitude, Cognition, and Capability, resulting in a unique "ACC model." This model indicates that this Chinese definition of digital leadership has gone beyond the traditional process-capability dichotomy and is a combination of three major constructs. "Practice or Policy:" This model provides a scientific foundation for the policymakers to develop "Digital Leadership Standards for Chinese Preschool Principals;" a conceptual structure of digital leadership for developing systematic indicators and scales. Digital leadership training can begin with an emphasis on attitude and cognition.

"Research Findings": This study aims to explore the optimal roles, pressing challenges, and future developments of ChatGPT in early childhood education (ECE) by interviewing six expert professors from China and the United States. A content analysis approach that combined inductive and deductive coding was employed to analyze the transcribed interviews. The findings of this study revealed two primary roles of ChatGPT in ECE: (1) conversational agent for young children and (2) on-call facilitator for educators and caregivers. The challenges and risks associated with ChatGPT were categorized using the "3A2S" framework, which includes Accessibility, Affordability, Accountability, Sustainability, and Social Justice. The participants suggest that as knowledge, information retrieval, and integration skills become less critical, human agency and inquiry ability become more important. As a result, they predict that ChatGPT's future trajectory should be as a resource for Intelligence Augmentation (IA) rather than as a replacement for the actions of educators and caregivers. Furthermore, AI opens new domains in ECE, such as AI literacy and AI social interaction, paving the way for novel opportunities and challenges in the field. "Practice or Policy": This study contributes to the ongoing discourse on integrating AI technologies in ECE and offers valuable suggestions for policymakers, educators, and caregivers.

"Research Findings": The Problematic Media Use Measure (PMUM) assesses young children's excessive or problematic media use. The current study aims to translate the original English version of PMUM into a Chinese version and validate it with Chinese preschoolers (ages 3 to 6). The instrument was translated, back-translated, pretested, and reviewed by a panel. The Chinese version of PMUM was administered to mothers of preschoolers (N = 1896). The results indicated that the construct validity of the PMUM was supported by the best-fit two-factor model: psychosocial problems and tolerance & withdrawal. Concurrent validity was established by demonstrating that: (1) the PMUM subscales scores were positively related to children's screen time and (2) the PMUM subscales scores were negatively related to parental mediation. The predictive validity of the PMUM subscales was also established: (1) the PMUM subscales scores were negatively correlated with prosocial behaviors, and (2) the PMUM subscales scores were positively correlated with emotional symptoms, hyperactivity/inattention, conduct problems, and peer relationship problems. Internal reliability and test-retest reliability were both satisfactory. "Practice or Policy": The findings support the further development and application of the PMUM to monitor children's media use and also emphasize the need for additional research on problematic media use.

This study examined the emergence of digital literacy in early childhood among 2272 parents with at least one child under age six in central China. Findings revealed that: (1) there was a significant age difference in early digital literacy, with television literacy emerging first, followed by touchscreen, artificial intelligence, and personal computer literacy. Gender differences were only observed in television literacy; (2) the home location, home income, home digital resource (HDR), and parent's age significantly correlated with young children's general emergent digital literacy, while family structure, parent's education, and occupation had significant correlations with some specific emergent digital literacy; HDR played a mediation role in the relationship between the home context factors and preschoolers' emergent digital literacy. (3) age of the child, family structure, home income, and HDR significantly contributed to predicting preschoolers'emergent digital literacy. Implications for policy-making and parental education are also addressed.

This study focuses on the online learning abilities of university students, a crucial skill in today's digital age. This research collected data from students (n = 945) from China with a questionnaire of 40 questions in two scales. The researchers made factor analyses concerning university students' online learning ability, which included 19 Likert scale questions, and the influencing factors on online learning ability, which had 15 Likert scale questions. The former analysis yielded two factors that explained the students' online learning ability: students' ability in self-regulation and innovation; and ability in technology control, and information processing. The latter yielded two factors influencing the students' online learning ability: using learning resources; external support. Comparative analyses were also made, with results showing that the independent variables of gender, educational level, major, and family economic situation significantly influenced certain variables.

This study assessed the impact of structural characteristics on quality rating and improvement systems (QRIS) outcomes in an Australian national study. Data from the Australian Children's Education and Care Quality Authority (ACECQA) repository of National Quality Standard (NQS) ratings were used to identify long day care services that had improved from Working Towards NQS to Meeting or Exceeding NQS or had no change over two assessments. QRIS outcomes were examined for state/territory jurisdiction, urban-rural location, community socio-economic status, type and size of provider organisation, centre size and stability of centre owner/provider using multinomial logistic regression analyses. Controlling for jurisdiction, results showed that improvement to Meeting NQS was more likely for not-for-profit versus for-profit providers and for large multi-site provider organisations versus small, stand-alone providers. Improvement to Exceeding NQS was also associated with not-for-profit and larger provider organisations, as well as larger versus smaller centres, and centres that had stable ownership.

Purpose: This study aimed to investigate the effectiveness and safety of endovascular revascularisation of intracranial artery occlusion and stenosis in moyamoya disease using stent angioplasty. Materials and methods: We recruited 12 patients (8 women and 4 men) with occlusion and stenosis of intracranial arteries in the context of moyamoya disease who underwent endovascular stent angioplasty. Clinical data, baseline conditions, lesion location, treatment outcomes, periprocedural complications, and follow-up outcomes were analysed. Results: The occlusion was located at the M1 segment of the middle cerebral artery in 8 patients, at both the M1 and A2 segments in one patient, and at the C7 segment of the internal carotid artery in 3. Thirteen stents were deployed at the occlusion site, including the low-profile visualized intraluminal support (LVIS) device in 8 patients, an LVIS device and a Solitaire AB stent in one, and a Leo stent in 3, with a success rate of 100% and no intraprocedural complications. Plain CT imaging after stenting revealed leakage of contrast agent, which disappeared on the second day, resulting in no clinical symptoms or neurological sequelae. Follow-up angiography studies were performed in all patients for 6–12 months (mean, 8.8). Slight asymptomatic in-stent stenosis was observed in 2 patients (16.7%), and no neurological deficits were observed in the other patients. All preoperative ischaemic symptoms completely disappeared at follow-up. Conclusion: Stent angioplasty is a safe and effective treatment for occlusion and stenosis of intracranial arteries in moyamoya disease. Resumen: Objetivos: Evaluamos la eficacia y la seguridad de la revascularización endovascular de oclusiones y estenosis de arterias intracraneales mediante angioplastia con stent en pacientes con enfermedad de moyamoya. Materiales y métodos: Incluimos a 12 pacientes (8 mujeres y 4 hombres) con oclusiones y estenosis de arterias intracraneales en el contexto de enfermedad de moyamoya que se sometieron a angioplastia con stent. Recogimos datos clínicos e información sobre enfermedades existentes, localización de la lesión, resultados terapéuticos, complicaciones periprocedimiento y resultados de seguimiento. Resultados: La oclusión afectaba al segmento M1 de la arteria cerebral media en 8 pacientes, a los segmentos M1 y A2 en un paciente, y al segmento C7 de la arteria carótida interna en los 3 restantes. Se colocaron 13 stents en el lugar de la oclusión: stents LVIS en 8 pacientes, un stent LVIS y un stent Solitaire AB en un paciente y stents Leo en 3 pacientes. La tasa de éxito fue del 100%, sin complicaciones durante el procedimiento. Una TC tras el procedimiento detectó fugas del medio de contraste, que desaparecieron al segundo día y no provocaron síntomas ni secuelas neurológicas. Se realizó un seguimiento de todos los pacientes con angiografía durante 6-12 meses (media: 8,8 meses). Dos pacientes (16,7%) presentaron una ligera reestenosis intrastent asintomática; el resto de los pacientes no presentaron déficits neurológicos. Todos los síntomas isquémicos previos desaparecieron durante el seguimiento. Conclusiones: La angioplastia con stent es un tratamiento eficaz y seguro de las oclusiones y estenosis de arterias intracraneales en pacientes con enfermedad de moyamoya.

The axial selection of tunnels constructed in the interlayered soft-hard rock mass affects the stability and safety during construction. Previous optimization is primarily based on experience or comparison and selection of alternative values under specific geological conditions. In this work, an intelligent optimization framework has been proposed by combining numerical analysis, machine learning (ML) and optimization algorithm. An automatic and intelligent numerical analysis process was proposed and coded to reduce redundant manual intervention. The conventional optimization algorithm was developed from two aspects and applied to the hyperparameters estimation of the support vector machine (SVM) model and the axial orientation optimization of the tunnel. Finally, the comprehensive framework was applied to a numerical case study, and the results were compared with those of other studies. The results of this study indicate that the determination coefficients between the predicted and the numerical stability evaluation indices (STIs) on the training and testing datasets are 0.998 and 0.997, respectively. For a given geological condition, the STI that changes with the axial orientation shows the trend of first decreasing and then increasing, and the optimal tunnel axial orientation is estimated to be 87°. This method provides an alternative and quick approach to the overall design of the tunnels.

Abstract We measured the Born cross sections for the process e + e − → ωη′ at 22 center-of-mass energies from 2.000 to 3.080 GeV with the BESIII detector at the BEPCII collider. We observed a resonant structure with a statistical significance of 9.6σ. A Breit-Wigner fit determines its mass to be M R = (2153 ± 30 ± 31) MeV/c 2 and its width to be Γ R = (167 ± 77 ± 7) MeV, where the first uncertainties are statistical and the second are systematic.

Abstract Background To evaluate a novel intraoperative localization technique utilizing temporary pulmonary arteriovenous occlusion for enhancing the precision of sublobar resections in early‐stage NSCLC. Methods Conducted from January to November 2023, this study involved 140 patients. During the surgery, key pulmonary vessels were identified using preoperative three‐dimensional (3D) imaging and temporarily occluded with noninvasive clamps to isolate the target lung segment. Following vascular occlusion, indocyanine green (ICG) was administered intravenously to precisely delineate the resection margins. After visually confirming the marked areas, the clamps were released, and a targeted partial resection was performed on the delineated segment. Surgical data, including operation times, surgical margins, and hospitalization costs, were collected and compared with those from a historical control group of 110 patients who underwent traditional pulmonary wedge resections. Results In the study group, the median surgical margin achieved was 16 mm, which was statistically significant compared to 15 mm in the control group (p

Achalinus sheni Ma, Xu, Qi, Wang, Tang, Huang & Jiang, 2023 was originally described based on only male specimens from Lianyuan City and Nanyue District, Hunan, China. So far, no information on the females of this species is available. After molecular systematics and morphological characters of recently collected specimens from Xinshao County, Hunan, several specimens (3 males and 1 female) were identified as this species. Therefore, we provided supplementary descriptions of the female characteristics of this species in this study. Meanwhile, we extended the description of this species.

Abstract This paper utilizes the theory of quantum diffusion to analyze the electron probability and spreading width of a wavepacket on each layer in a two-dimensional (2D) coupled system with edge disorder, aiming to clarify the effects of edge disorder on the stability of the electron periodic oscillations in 2D coupled systems. Using coupled 2D square lattices with edge disorder as an example, we show that, the electron probability and wavepacket spreading width exhibit periodic oscillations and damped oscillations, respectively, before and after the wavepacket reaches the boundary. Furthermore, these electron oscillations exhibit strong resistance against disorder perturbation with a longer decay time in the regime of large disorder, due to the combined influences of ordered and disordered site energies in the central and edge regions. Finally, we numerically verified the universality of the results through bilayer graphene, demonstrating that this anomalous quantum oscillatory behavior is independent of lattice geometry. Our findings are helpful in designing relevant quantum devices and understanding the influence of edge disorder on the stability of electron periodic oscillations in 2D coupled systems.

Abstract Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.

AIM: To explore the effect of silent information regulator factor 2-related enzyme 1 (SIRT1) on modulating apoptosis of human lens epithelial cells (HLECs) and alleviating lens opacification of rats through suppressing endoplasmic reticulum (ER) stress. METHODS: HLECs (SRA01/04) were treated with varying concentrations of tunicamycin (TM) for 24h, and the expression of SIRT1 and C/EBP homologous protein (CHOP) was assessed using real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8 (CCK-8) assay, respectively. In the SRA01/04 cell apoptosis model, which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation, the expression levels of SIRT1, CHOP, glucose regulated protein 78 (GRP78), and activating transcription factor 4 (ATF4) were examined. The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid (4-PBA; an ER stress inhibitor) was investigated. In vivo, age-related cataract (ARC) rat models were induced by sodium selenite injection, and the protective role of SIRT1, activated by SRT1720 intraperitoneal injections, was evaluated through morphology observation, hematoxylin and eosin (H&E) staining, Western blotting, and RT-PCR. RESULTS: SIRT1 expression was downregulated in TM-induced SRA01/04 cells. Besides, in SRA01/04 cells, both cell apoptosis and CHOP expression increased with the rising doses of TM. ER stress was stimulated by TM, as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model. Inhibition of SIRT1 by siRNA knockdown increased ER stress activation, whereas SRT1720 treatment had opposite results. 4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis. In vivo, SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models. CONCLUSION: SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress. These findings suggest a novel strategy for cataract treatment focused on targeting ER stress, highlighting the therapeutic potential of SIRT1 modulation in ARC development.

In order to investigate the important functional-active components in different varieties of natto, natto was processed using soybean, black bean, red bean, mung bean, lentil, chickpea, kidney bean, pea, red bean and cowpea, and the differences of nattokinase, polyphenol, natto polysaccharide and γ-aminobutyric acid were compared and analyzed in these natto. The results showed that the nattokinase activity ranged from 985.31 to 2453.18 U/g, and the nattokinase activity in chickpea natto was significantly higher than those of other natto (P

Abstract The second-order nonlinear Hall effect (NLHE) in non-centrosymmetric materials has recently drawn intense interest, since its inherent rectification could enable various device applications such as energy harvesting and wireless charging. However, previously reported NLHE systems normally suffer from relatively small Hall voltage outputs and/or low working temperatures. In this study, we report the observation of a pronounced NLHE in tellurium (Te) thin flakes at room temperature. Benefiting from the semiconductor nature of Te, the obtained nonlinear response can be readily enhanced through electrostatic gating, leading to a second-harmonic output at 300 K up to 2.8 mV. By utilizing such a giant NLHE, we further demonstrate the potential of Te as a wireless Hall rectifier within the radiofrequency range, which is manifested by the remarkable and tunable rectification effect also at room temperature. Extrinsic scattering is then revealed to be the dominant mechanism for the NLHE in Te, with symmetry breaking on the surface playing a key role. As a simple elemental semiconductor, Te provides an appealing platform to advance our understanding of nonlinear transport in solids and to develop NLHE-based electronic devices.

Abstract Objective Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging‐related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera–Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM‐BAge and PhenoAge‐BAge measures based on the Levine method. The KDM‐AAge and PhenoAge‐AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results During a median follow‐up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000–1.223) for KDM‐AAge and 1.180 (95% CI, 1.068–1.303) for PhenoAge‐AAge, respectively. For PhenoAge‐AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374–2.639) in males with CAge

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) has high mortality rates. The osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK)/Toll-like receptor 4 (TLR4) pathway and its potential role in SA-AKI pathogenesis remain to be fully understood. Herein, we addressed this issue using mouse models. Methods An SA-AKI mouse model was established using the cecal ligation and puncture method (CLP). Mice were grouped into sham, CLP model, CLP + recombinant RANKL, and CLP + anti-RANKL groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured to assess kidney function. ELISA was used to detect serum IL-1β, TNF-α, and IL-6 levels. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of OPG, RANKL, RANK, and TLR4 in kidney tissues. HE staining was performed to evaluate the pathological changes. Results The CLP model group showed higher levels of Scr and BUN, indicating impaired kidney function in SA-AKI, compared to the sham group. Treatment with recombinant RANKL in the CLP + recombinant RANKL group reduced Scr and BUN levels, while anti-RANKL treatment in the CLP + anti-RANKL group elevated their levels. Moreover, the CLP model group had significantly increased IL-1β, TNF-α, and IL-6 than the sham group, indicating elevated inflammation in SA-AKI. The CLP + recombinant RANKL group demonstrated decreased cytokine levels, whereas the CLP + anti-RANKL group showed an increase. Additionally, the histopathological evaluation revealed distinct kidney tissue damage in the CLP model group. Recombinant RANKL treatment reduced this damage, while anti-RANKL treatment exacerbated it. Mechanically, the mRNA and protein expression of RANKL were significantly decreased, while those of OPG, RANK, and TLR4 were significantly increased in the CLP model group and the CLP + anti-RANKL group. Interestingly, treatment with recombinant RANKL reversed these changes, as evidenced by significantly increased RANKL but decreased OPG, RANK, and TLR4. Conclusion The OPG/RANKL/RANK/TLR4 pathway is involved in SA-AKI pathogenesis. Recombinant RANKL treatment attenuates the inflammatory response and kidney tissue damage in SA-AKI, possibly via regulating this pathway. This pathway shows promise as a therapeutic target for SA-AKI.

Abstract There are no targeted rehabilitation training modalities and assessment tools for patients after transoral endoscopic thyroidectomy vestibular approach (TOETVA). Herein, we develop a new assessment questionnaire and rehabilitation training modality and evaluate its safety and effectiveness. The THYCA-QoL-TOETVA questionnaire was compiled, and reliability and validity analyses were performed. Patients were divided into the new rehabilitation training group (N) or the conventional rehabilitation training group (C), and 1:1 propensity score matching (PSM) was performed after administering questionnaires to patients in both groups. Cervical range of motion (CROM) data were also measured and collected for statistical analysis. The questionnaire used in this study showed good expert authority, coordination, internal consistency, and questionnaire reliability. A total of 476 patients were included after PSM, and the questionnaire results showed that recovery and quality of life were better in the N group than in the C group (124.55 ± 8.171 vs. 122.94 ± 8.366, p = 0.026). Analysis of cervical spine mobility showed that rehabilitation was better in the N group compared to the C group at postoperative one month (flexion: 1.762°, extension: 4.720°, left lateral bending: 3.912°, right lateral bending: 4.061°, left axial rotation: 5.180°, right axial rotation: 5.199°, p value all of these

Abstract Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

Flowering time is important for adaptation of soybean (Glycine max) to different environments. Here, we conducted a genome-wide association study of flowering time using a panel of 1490 cultivated soybean accessions. We identified three strong signals at the qFT02-2 locus (Chr02: 12037319–12238569), which were associated with flowering time in three environments: Gongzhuling, Mengcheng, and Nanchang. By analyzing linkage disequilibrium, gene expression patterns, gene annotation, and the diversity of variants, we identified an AP1 homolog as the candidate gene for the qFT02-2 locus, which we named GmAP1d. Only one nonsynonymous polymorphism existed among 1490 soybean accessions at position Chr02:12087053. Accessions carrying the Chr02:12087053-T allele flowered significantly earlier than those carrying the Chr02:12087053-A allele. Thus, we developed a cleaved amplified polymorphic sequence (CAPS) marker for the SNP at Chr02:12087053, which is suitable for marker-assisted breeding of flowering time. Knockout of GmAP1d in the ‘Williams 82’ background by gene editing promoted flowering under long-day conditions, confirming that GmAP1d is the causal gene for qFT02-2. An analysis of the region surrounding GmAP1d revealed that GmAP1d was artificially selected during the genetic improvement of soybean. Through stepwise selection, the proportion of modern cultivars carrying the Chr02:12087053-T allele has increased, and this allele has become nearly fixed (95%) in northern China. These findings provide a theoretical basis for better understanding the molecular regulatory mechanism of flowering time in soybean and a target gene that can be used for breeding modern soybean cultivars adapted to different latitudes.

Objective: This study aims to explore the relationship between different endometrial preparations and pregnancy outcomes among patients with regular ovulatory cycles in order to find the best endometrial preparation methods in the freeze–thaw embryo transfer (FET) cycle. Materials and Methods: This is a retrospective study to investigate FET pregnancy outcomes in women who had a regular menstrual cycle, were younger than 35 years old, and underwent a modified natural cycle (mNC), ovulation induction (OI), or a hormone replacement treatment (HRT) cycle. A total of 1071 frozen cycles were included for analysis. Results: The implantation rate and live birth rate (LBR) in the OI group show a significant difference when compared to the mNC and HRT groups (P < 0.01). After adjusting for confounding factors, the logistic regression analysis revealed that the number of embryos transferred, the embryo stage, and quality were significantly associated with clinical pregnancy rate and LBR. The LBR was additionally affected by the mode of the endometrial preparation; the OI cycle could increase LBR. Conclusions: Endometrial preparation methods affect the LBR in women with a regular menstrual cycle. The OI cycle had an advantage in the LBR of FET.

Abstract Background Arterial injury caused by heterotopic ossification (HO) following fractures is rarely reported, yet it can have catastrophic consequences. This case report presents a unique instance of femoral artery injury and hematoma organization, occurring a decade after intramedullary nail fixation for a femoral shaft fracture complicated by HO. Case presentation A 56-year-old male presented with right femoral artery injury and organized hematoma, a decade after suffering bilateral femoral shaft fractures with mild head injury in a traffic accident. He had received intramedullary nailing for the right femoral shaft fracture and plate fixation for the left side in a local hospital. Physical examination revealed two firm, palpable masses with clear boundaries, limited mobility, and no tenderness. Peripheral arterial pulses were intact. Radiography demonstrated satisfactory fracture healing, while a continuous high-density shadow was evident along the inner and posterior aspect of the right thigh. Computed tomography angiography identified a large mixed-density mass (16.8 × 14.8 × 20.7 cm) on the right thigh’s medial side, featuring central calcification and multiple internal calcifications. The right deep femoral artery coursed within this mass, with a smaller lesion noted on the posterior thigh. Surgical consultation with a vascular surgeon led to planned intervention. The smaller mass was completely excised, but the larger one partially, as it encased the femoral artery. The inability to remove all HO was due to excessive bleeding. Postoperatively, the patient experienced no complications, and one-year follow-up revealed a favorable recovery with restoration of full right lower limb mobility. Conclusion This case underscores the potential gravity of vascular injury associated with heterotopic ossification. Surgeons should remain vigilant regarding the risk of vascular injury during HO excision.

Abstract Diabetic foot ulcer (DFU) is a leading cause of high-level amputation in DM patients, with a low wound healing rate and a high incidence of infection. Vascular endothelial growth factor (VEGF) plays an important role in diabetes mellitus (DM) related complications. This study aims to explore the VEGF expression and its predictive value for prognosis in DFU, in order to provide basis for the prevention of DFU related adverse events. We analyzed 502 patients, with 328 in healing group and 174 in non-healing/recurrent group. The general clinical data and laboratory indicators of patients were compared through Spearman correlation analysis, ROC analysis and logistic regression analysis. Finally, the independent risk factors for adverse prognosis in DFU patients were confirmed. Spearman analysis reveals a positive correlation between the DFU healing rate and ABI, VEGF in wound tissue, and positive rate of VEGF expression, and a negative correlation with DM duration, FPG, HbA1c, TC, Scr, BUN, and serum VEGF. Further logistic regression analysis finds that the DM duration, FPG, HbA1c, ABI, serum VEGF, VEGF in wound tissue, and positive rate of VEGF expression are the independent risk factors for adverse prognosis in DFU (p

Abstract Background The modified pancreatitis activity scoring system (mPASS) was proposed to assess the activity of acute pancreatitis (AP) while it doesn’t include indicators that directly reflect pathophysiology processes and imaging characteristics. Objectives To determine the threshold of admission mPASS and investigate radiomics and laboratory parameters to construct a model to predict the activity of AP. Methods AP inpatients at institution 1 were randomly divided into training and validation groups based on a 5:5 ratio. AP inpatients at Institution 2 were served as test group. The cutoff value of admission mPASS scores in predicting severe AP was selected to divide patients into high and low level of disease activity group. LASSO was used in screening features. Multivariable logistic regression was used to develop radiomics model. Meaningful laboratory parameters were used to construct combined model. Results There were 234 (48 years ± 10, 155 men) and 101 (48 years ± 11, 69 men) patients in two institutions. The threshold of admission mPASS score was 112.5 in severe AP prediction. The AUC of the radiomics model was 0.79, 0.72, and 0.76 and that of the combined model incorporating rad-score and white blood cell were 0.84, 0.77, and 0.80 in three groups for activity prediction. The AUC of the combined model in predicting disease without remission was 0.74. Conclusions The threshold of admission mPASS was 112.5 in predicting severe AP. The model based on CECT radiomics has the ability to predict AP activity. Its ability to predict disease without remission is comparable to mPASS. Critical relevance statement This work is the first attempt to assess the activity of acute pancreatitis using contrast-enhanced CT radiomics and laboratory parameters. The model provides a new method to predict the activity and prognosis of AP, which could contribute to further management. Key Points Radiomics features and laboratory parameters are associated with the activity of acute pancreatitis. The combined model provides a new method to predict the activity and prognosis of AP. The ability of the combined model is comparable to the modified Pancreatitis Activity Scoring System. Graphical Abstract

Abstract Nanoplasmas induced by intense laser fields have attracted enormous attention due to their accompanied spectacular physical phenomena which are vigorously expected by the community of science and industry. For instance, the energetic electrons and ions produced in laser-driven nanoplasmas are significant for the development of compact beam sources. Nevertheless, effective confinement on the propagating charged particles, which was realized through magnetic field modulation and target structure design in big facilities, are largely absent in the microscopic regime. Here we introduce a reliable scheme to provide control on the emission direction of protons generated from surface ionization in gold nanoparticles driven by intense femtosecond laser fields. The ionization level of the nanosystem provides us a knob to manipulate the characteristics of the collective proton emission. The most probable emission direction can be precisely steered by tuning the excitation strength of the laser pulses. This work opens new avenue for controlling the ion emission in nanoplasmas and can vigorously promote the fields such as development of on-chip beam sources at micro-/nano-scales.

Abstract Background Getting lost with family members who have dementia is a significant source of stress for family caregivers. In Taiwan, family caregivers develop strategies to deal with dementia persons who may get lost. This study aimed to explore the experiences of family caregivers caring for persons with dementia who have been lost outside the home. Methods A descriptive phenomenological method was used. The COREQ checklist was used to ensure the explicit reporting of data. A total of 20 family caregivers caring for persons with dementia who were lost outside their homes were selected from hospital outpatient clinics and a day care center in northern Taiwan using purposive sampling. Data were analyzed using the Giorgi analysis method. Results Five main themes emerged: (i) surprised persons with dementia lost outside, (ii) using strategies to prevent persons with dementia from getting lost, (iii) using strategies to find lost persons with dementia, (iv) exhaustion in long-term care persons with dementia, and (v) coping with the care load. It was found that family caregivers were surprised, nervous, and worried about persons with dementia being lost outside. They used the first strategy to supervise persons with dementia to prevent external losses. In addition, long-term supervision of persons with dementia led to mental exhaustion in the family caregivers. Finally, the family caregivers learned about loss prevention strategies and obtained family support and care replacement workers to reduce the care burden. Conclusions It is essential to teach family caregivers early to prevent persons with dementia from losing external strategies. Nurses also provide long-term care services to reduce the care burden on family caregivers.

Abstract Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration. Graphical Abstract

Taking the deep-ultra deep glutenite reservoirs in the Upper Wuerhe Formation of Permian in Fukang Sag and Dongdaohaizi Sag as the research object and representative of the eastern Junggar Basin, its characteristics and main controlling factors are analyzed using various methods, including core analysis, thin section examination, and scanning electron microscope observation. High-pressure mercury injection and logging imaging were also employed to reveal the reservoir that Fukang and Dongdaohaizi sags harbor deep-ultra deep glutenite reservoirs, with Fukang Sag being a typical low porosity to ultra-low permeability reservoir, while Dongdaohaizi Sag is a low porosity to low permeability reservoir. Reservoir space types vary between the two sags, with Fukang Sag characterized by microfractures and corrosion pores, while a large number of corrosion pores with fewer fractures existing in Dongdaohaizi Sag. Both compaction and cementation exhibit a strong destructive effect on the reservoirs in the eastern Junggar Basin. However, the compaction effect in Fukang Sag is very strong, and the dissolution effect is weak. The large number of fractures generated by overpressure becomes an effective channel for ultra-deep oil and gas migration. The cracks in the Dongdaohaizi Sag are underdeveloped, and a large number of intra-particle corrosion pores generated by the dissolution of feldspar and turbidite improve reservoir properties. In addition, its rich turbidite also plays a compressive and pore retention role. There are two types of reservoir models developed in the Upper Wuerhe Formation of Permian in the eastern Junggar Basin: the deep fracture model represented by the Fukang Sag and the solution pore model rich in turbidite in Dongdaohaizi Sag. These models create favorable conditions for oil and gas accumulation in the deep-ultra deep reservoirs in the depression area.

Based on the organic geochemical data and the molecular and stable carbon isotopic compositions of natural gas of the Lower Permian Fengcheng Formation in the western Central Depression of Junggar Basin, combined with sedimentary environment analysis and hydrocarbon-generating simulation, the gas-generating potential of the Fengcheng source rock is evaluated, the distribution of large-scale effective source kitchen is described, the genetic types of natural gas are clarified, and four types of favorable exploration targets are selected. The results show that: (1) The Fengcheng Formation is a set of oil-prone source rocks, and the retained liquid hydrocarbon is conducive to late cracking into gas, with characteristics of high gas-generating potential and late accumulation; (2) The maximum thickness of Fengcheng source rock reaches 900 m. The source rock has entered the main gas-generating stage in Penyijingxi and Shawan sags, and the area with gas-generating intensity greater than 20×108 m3/km2 is approximately 6 500 km2. (3) Around the western Central Depression, highly mature oil-type gas with light carbon isotope composition was identified to be derived from the Fengcheng source rocks mainly, while the rest was coal-derived gas from the Carboniferous source rock; (4) Four types of favorable exploration targets with exploration potential were developed in the western Central Depression which are structural traps neighboring to the source, stratigraphic traps neighboring to the source, shale-gas type within the source, and structural traps within the source. Great attention should be paid to these targets.

Elevated levels of high mobility group protein B1 (HMGB1) play a significant role in the pathogenesis of many diseases, but is particularly important for the formation of malignant tumors. Nonetheless, the function of HMGB1 and the underlying mechanism of laryngeal squamous cell carcinoma (LSCC) remain incompletely understood, causing uncertainty. Here we found immunohistochemistry from 97 LSCC tissues showed HMGB1 was upregulated, which was associated with poor differentiation. HMGB1 knockdown could significantly inhibit wound closure and colony formation. The full-genome gene expression microarray was performed to investigate the mechanism. After knockdown of HMGB1 by siRNA, among the expressed differential genes, 10 genes were randomly selected for validation. Then, shRNA lentivirus targeting these genes were constructed to explore their role in LSCC by cell proliferation assay. LSM6 downregulation was dramatically promoted by HMGB1 knockdown, resulting in higher expression in LSCC tissues. Furthermore, downregulation of LSM6 could significantly suppress cell proliferation, migration and colony formation. This study indicated that HMGB1 promoted LSCC cell malignant phenotypes through regulation of LSM6. We anticipate that HMGB1-LSM6 could be a putative therapeutic target for LSCC.

Abstract In machine learning (ML) problems, it is widely believed that more training samples lead to improved predictive accuracy but incur higher computational costs. Consequently, achieving better data efficiency, that is, the trade-off between the size of the training set and the accuracy of the output model, becomes a key problem in ML applications. In this research, we systematically investigate the data efficiency of Univariate Time Series Anomaly Detection (UTS-AD) models. We first experimentally examine the performance of nine popular UTS-AD algorithms as a function of the training sample size on several benchmark datasets. Our findings confirm that most algorithms become more accurate when more training samples are used, whereas the marginal gain for adding more samples gradually decreases. Based on the above observations, we propose a novel framework called FastUTS-AD that achieves improved data efficiency and reduced computational overhead compared to existing UTS-AD models with little loss of accuracy. Specifically, FastUTS-AD is compatible with different UTS-AD models, utilizing a sampling- and scaling law-based heuristic method to automatically determine the number of training samples a UTS-AD model needs to achieve predictive performance close to that when all samples in the training set are used. Comprehensive experimental results show that, for the nine popular UTS-AD algorithms tested, FastUTS-AD reduces the number of training samples and the training time by 91.09–91.49% and 93.49–93.82% on average without significant decreases in accuracy.

Abstract Background/purpose(s) The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. Methods We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. Results Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. Conclusion Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies. Graphical Abstract

Bacillus subtilis and Lactobacillus casei were commonly used in the production of fermented bean products. The effects of fermentation by two types of bacteria on the hypoglycemic and lipid-lowering activities of crude polysaccharides from bean flour were analyzed. In this study, 8 kinds of crude polysaccharide samples from fermented edible beans by the two types of bacteria were prepared. And the composition, water solubility, in vitro hypoglycemic and lipid-lowering activity of crude polysaccharides from before and after bean flour fermentation by the two types of bacteria were compared and analyzed. The results showed that the content of uronic acid in the crude polysaccharide from fermented bean flour increased. The content of uronic acid in the crude polysaccharides from fermented bean flour by Bacillus subtilis (4.05%~22.46%) was significantly higher than that of the crude polysaccharides from fermented bean flour by Lactobacillus casei (2.63%~10.72%) (P

Abstract Background Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages. Methods Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2 production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity. Results CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1β and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection. Conclusion CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.

Abstract Objective To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. Methods An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. Results The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p

Abstract Introduction Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer. The presence of lymph node metastasis plays a crucial role in determining the overall treatment approach and long‐term prognosis for early LUAD, therefore accurate prediction of lymph node metastasis is essential to guide treatment decisions and ultimately improve patient outcomes. Methods We performed transcriptome sequencing on T1 LUAD patients with positive or negative lymph node metastases and combined this data with The Cancer Genome Atlas Program cohort to identify potential risk molecules at the tissue level. Subsequently, by detecting the expression of these risk molecules by real‐time quantitative PCR in serum samples, we developed a model to predict the risk of lymph node metastasis from a training cohort of 96 patients and a validation cohort of 158 patients. Results Through transcriptome sequencing analysis of tissue samples, we identified 11 RNA (miR‐412, miR‐219, miR‐371, FOXC1, ID1, MMP13, COL11A1, PODXL2, CXCL13, SPOCK1 and MECOM) associated with positive lymph node metastases in T1 LUAD. As the expression of FOXC1 and COL11A1 was not detected in serum, we constructed a predictive model that accurately identifies patients with positive lymph node metastases using the remaining nine RNA molecules in the serum of T1 LUAD patients. In the training set, the model achieved an area under the curve (AUC) of 0.89, and in the validation set, the AUC was 0.91. Conclusions We have established a new risk prediction model using serum samples from T1 LUAD patients, enabling noninvasive identification of those with positive lymph node metastases.

We de novo assembled and analysed the chloroplast genomes of Capsella bursa-pastoris, Descurainia sophia, and Lepidium apetalum of the plant family Brassicaceae. These chloroplast genomes exhibited a quadripartite structure characterised by inverted repeat regions (26,268–26,460 bp) separating large single copy (83,771–83,870 bp) and small single copy (17,570–18,014 bp) regions. Genetic analysis revealed 112 unique genes, comprising 78 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. Notably, phylogenetic analysis of 21 species revealed close relationships between C. bursa-pastoris and C. orientalis, D. sophia and D. erodiifolia, and L. apetalum and L. cordatum, with 100% bootstrap support. In conclusion, the analysis of these genomes will contribute to the growing knowledge of chloroplast genomes in the Brassicaceae family and of the specific genera Capsella, Descurainia, and Lepidium.

This study sought to determine the effects of rosemary leaf powder (RP) on laying performance, egg quality, serum indices, gut barrier function, and cecal microbiota and metabolites of late-phase laying hens. A total of 84 “Jing Tint 6” laying hens at 65-week old were randomly divided into 2 groups and fed either a basal diet (CON) or a basal diet supplemented with 0.3% RP. Our study revealed that RP improved the Haugh unit and decreased yolk n-6/n-3 polyunsaturated fatty acid (PUFA) ratio of laying hens, increased serum superoxide dismutase (SOD), jejunal activities of SOD and catalase (CAT), and jejunal zonula occludens-1 (ZO-1) expression, as well as decreased serum tumor necrosis factor-α (TNF-α) level and jejunal TNF-α mRNA expression. Rosemary leaf powder markedly enhanced (P

The formation of humins hampers the large-scale production of 5-hydroxymethylfurfural (HMF) in biorefinery. Here, a detailed reaction network of humin formation at the initial stage of fructose-to-HMF dehydration in water is delineated by combined experimental, spectroscopic, and theoretical studies. Three bimolecular reaction pathways to build up soluble humins are demonstrated. That is, the intermolecular etherification of β-furanose at room temperature initiates the C12 path, whereas the C–C cleavage of α-furanose at 130–150 °C leads to C11 path, and that of open-chain fructose at 180 °C to C11′ path. The successive intramolecular dehydrations and condensations of the as-formed bimolecular intermediates lead to three types of soluble humins. We show that the C12 path could be restrained by using HCl or AlCl3 catalyst, and both the C12 and C11′ paths could be effectively inhibited by adding THF as a co-solvent or accelerating heating rate via microwave heating.