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PurposeVitamin D deficiency is frequent in patients with multiple myeloma (MM), however, its prognostic relevance in MM was rather inconclusive. We first investigated the association of vitamin D deficiency with abnormal bone and lipid metabolism in newly diagnosed multiple myeloma (NDMM), and next assessed the impact of serum ratio of vitamin D to carboxy-terminal telopeptide of type I collagen (β-CTX) on progression-free survival (PFS) and overall free survival (OS) in patients with NDMM.MethodsThe data of 431 consecutive patients with NDMM at Beijing Jishuitan Hospital from September 2013 to December 2022 were collected and retrospectively reviewed through our electronic medical record system. The measurement of 25-hydroxyvitamin D in the blood is an indicator of an individual’s overall vitamin D status.ResultsThe serum levels of vitamin D were negatively correlated with β-CTX in NDMM patients. Of note, positive correlation between vitamin D and cholesterol levels in the serum was found in this study. The cohort (n = 431) was divided into two groups based on the serum ratio of vitamin D to β-CTX. Compared to the group with a higher vitamin D to β-CTX ratio, the group with a lower vitamin D to β-CTX ratio (n = 257, 60%) exhibited hypocholesterolemia, inferior PFS and OS, along with increased cases of ISS stage-III and R-ISS stage-III, a higher number of plasma cells in the bone marrow, and elevated serum calcium levels. Consistent with this, multivariate analysis confirmed that the vitamin D to β-CTX ratio was an independent unfavorable indicator for survival in NDMM patients.ConclusionOur data demonstrated the ratio of vitamin D to β-CTX in the serum is a unique biomarker for NDMM patients to identify the high-risk cases with poor prognosis, which is superior to vitamin D itself for predicting PFS and OS in NDMM. Also, it is worth mentioning that our data on the connection between vitamin D deficiency and hypocholesterolemia might help clarify novel mechanistic aspects of myeloma development.

Cutaneous delayed drug hypersensitivity reactions (DHRs) are common iatrogenic events with potentially life-threatening consequences. Delayed DHRs encompass diverse phenotypes and can be classified by their distinct T-cell responses to drug antigens. Interaction between the immune receptors, human leukocyte antigen (HLA) and T-cell receptor (TCR), and the complementary antigenic peptide is required for the development of delayed DHRs. These idiosyncratic interactions can be elicited by the formation of antigenic drug-protein adducts (hapten hypothesis) or from direct interactions of drugs with the immune receptors (pharmacological interaction of drugs with immune receptors concept, altered peptide repertoire model, and altered TCR model). In addition, viral infections may play a role by providing co-stimulatory signals or enhancing TCR/HLA expression on T-cells. The associations of HLA allele polymorphisms and DHRs are phenotype and ethnicityspecific. The discovery of genetic polymorphisms associated with DHRs has provided a strategy to prevent and diagnose potentially life-threatening reactions. Recently, advances in next-generation sequencing technologies, such as the incorporation of whole-exome or whole-genome sequencing, enabled the comprehensive detection of susceptibility loci. Several HLA associations have shown clinical utility and cost-effectiveness, such as HLA-B*15:02 (carbamazepine-induced Stevens–Johnson syndrome/toxic epidermal necrolysis in Han Chinese), HLA-B*58:01 (allopurinol-induced severe cutaneous adverse reactions in Han Chinese), HLA-B*57:01 (abacavir hypersensitivity reactions in Caucasians), and HLA-B*13:01 (dapsone-induced drug reaction with eosinophilia and systemic symptoms in Han Chinese). Herein, we summarize the current knowledge of the pathogenesis, antigen presentation models, and HLA associations of cutaneous delayed DHRs.

Background: The midfacial fat is highly compartmentalized, and the deep fat compartments provide structural support for the midface. Understanding the age-related changes in the midfacial deep fat compartments is important for midfacial rejuvenation physiologically. However, previous studies showed conflicted results of these changes. Objectives: This study aims to quantify the age-related changes of deep fat compartments in the midface using ultrasound. Methods: A cross-sectional study was conducted to evaluate subjects with age more than 25 years old and the subjects were divided into four age groups equally (25–34, 35–44, 45–54, and ≥55). The thickness of the suborbicularis oculi fat compartment (SOOF) and deep medial cheek fat compartment (DMCF) was measured using a portable ultrasound device. Mean thickness differences among different age groups were analyzed by one-way analysis of variance. Multiple linear regression adjusted for body mass index (BMI) and sex was also conducted. Results: A total of 60 subjects were enrolled. The thickness of SOOF and DMCF tends to decrease with age. The mean decrease of SOOF and DMCF from the youngest group to the oldest group was 0.63 mm (36%) and 0.70 mm (25.83%), respectively. The relationship between aging and thickness of SOOF and DMCF remains significant after adjusting for BMI and sex (both P < 0.001). Conclusion: The thickness of deep fat compartments decreases with the natural aging process. The study may offer clinical implications for targeted volume rejuvenation to achieve a more youthful and natural face.

Drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome (DRESS/DIHS) is one type of severe cutaneous adverse reaction (SCAR). It is featured by fever, widespread skin lesions, protracted clinical course, internal organ involvement, and possibly long-term autoimmune sequelae. The presence of high-risk human leukocyte antigen (HLA) alleles, hypersensitivity reaction after culprit drug ingestion, and human herpesvirus reactivation may all contribute to its complex clinical manifestations. Some recent studies focusing on the roles of involved cytokines/chemokines and T cells co-signaling pathways in DRESS/DIHS were conducted. In addition, some predictors of disease severity and prognosis were also reported. In this review, we provided an update on the current understanding of the pathogenesis, potential biomarkers, and the relevant therapeutic rationales of DRESS/DIHS.

Higher rates of postoperative complications have been found in preoperative chronic steroid users. However, the effects of preoperative chronic steroid use on outcomes in orthopedic surgery were unclear. We performed a systematic review of cohort studies examining the effects of chronic steroid use on postoperative outcomes following orthopedic surgery and searched PubMed, Embase, and CENTRAL through 29 April 2023. We included 17 studies with 1,546,562 patients. No increase in 30-day mortality (adjusted odds ratio (aOR) 1.40, 95% confidence interval (CI) 0.64–3.09) and composite thromboembolic events (aOR 1.61, 95% CI 0.99–2.63) but increases in 30-day overall complications (aOR 1.42, 95% CI 1.16–1.75), wound dehiscence (aOR 2.91, 95% CI 1.49–5.66), infectious complications (any infection (aOR 1.61, 95% CI 1.44–1.80), sepsis (aOR 2.07, 95% CI 1.34–3.21), superficial surgical site infection (SSI) (aOR 1.73, 95% CI 1.03–2.89) and deep SSI (aOR 1.96, 95% CI 1.26–3.05)), re-admission (aOR 1.62, 95% CI 1.48–1.77), both 30-day (aOR 1.28, 95% CI 1.03–1.59) and 1-year re-operation (aOR 1.78, 95% CI 1.09–2.92), pulmonary embolism (aOR 5.94, 95% CI 1.52–23.29), and deep vein thrombosis (aOR 2.07, 95% CI 1.24–3.46) were detected in preoperative steroid users. An increased risk of adverse outcomes following orthopedic surgery in chronic steroid users was found.

Abstract Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin‐like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self‐renewal, protein expression of c‐MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts. The addition of exogenous cholesterol fully restores PODXL knockdown‐mediated loss of pluripotency. PODXL affects lipid raft dynamics via the regulation of cholesterol. PODXL recruits the RAC1/CDC42/actin network to regulate SREBP1 and SREBP2 maturation and lipid raft dynamics. Single‐cell RNA sequencing reveals PODXL overexpression enhanced chimerism between human cells in mouse host embryos (hEPSCs 57%). Interestingly, in the human–mouse chimeras, laminin and collagen signaling‐related pathways are dominant in PODXL overexpressing cells. It is concluded that cholesterol regulation via PODXL signaling is critical for ESC/EPSC.

miR-126 is highly expressed in inv(16) Acute myeloid leukemia (AML) but its role is unclear. Here, the authors show that the aberrant expression of miR-126 in inv(16) AML is directly due to the CBFB-MYH11 fusion gene and that it can promote AML development and leukemia stem cell maintenance, highlighting miR-126 as a therapeutic target for inv(16) AML patients

Fused deposition modeling (FDM) is a form of additive manufacturing where three-dimensional (3D) models are created by depositing melted thermoplastic polymer filaments in layers. Although FDM is a mature process, defects can occur during printing. Therefore, an image-based quality inspection method for 3D-printed objects of varying geometries was developed in this study. Transfer learning with pretrained models, which were used as feature extractors, was combined with ensemble learning, and the resulting model combinations were used to inspect the quality of FDM-printed objects. Model combinations with VGG16 and VGG19 had the highest accuracy in most situations. Furthermore, the classification accuracies of these model combinations were not significantly affected by differences in color. In summary, the combination of transfer learning with ensemble learning is an effective method for inspecting the quality of 3D-printed objects. It reduces time and material wastage and improves 3D printing quality.

Biphotons, generated from a hot atomic vapor via the process of spontaneous four-wave mixing (SFWM), have the following merits: Stable and tunable frequencies as well as linewidth. Such merits are very useful in the application of long-distance quantum communication. However, the hot-atom SFWM biphoton sources previously had far lower values of generation rate per linewidth, i.e., spectral brightness, as compared with the sources of biphotons generated by the spontaneous parametric down-conversion process. Here we report a hot-atom SFWM source of biphotons with a linewidth of 960 kHz and a generation rate of 3.7×10^{5} pairs/s. The high generation rate, together with the narrow linewidth, results in a spectral brightness of 3.8×10^{5} pairs/s/MHz, which is 17 times the previous best result with atomic vapors and also better than all known results with all kinds of media. The all-co-propagating scheme together with a large optical depth (OD) of the atomic vapor is the key improvement, enabling the achieved spectral brightness to be about one quarter of the ultimate limit. Furthermore, this biphoton source had a signal-to-background ratio (SBR) of 2.7, which violated the Cauchy-Schwartz inequality for classical light by about 3.6-fold. Although an increasing spectral brightness usually leads to a decreasing SBR, our systematic study indicates that both of the present spectral brightness and SBR can be enhanced by further increasing the OD. This work demonstrates a significant advancement and provides useful knowledge in quantum technology using photons.

Abstract  Time synchronization plays a key role in the wireless sensor networks (WSNs). Time synchronization is realized by those messages that are time-stamped. But there are several delay times during transmission after time stamping. Most of them are uncertain and contribute directly to synchronization error. The uncertainties include send time, channel access time, transmission time, and receive time. In addition to the uncertainties, clock drift is also a main source of time synchronization error. In this paper, we present a time synchronization protocol that can be applied in the multi-hop WSNs. The proposed protocol estimates the clock drift between two nodes to keep them synchronized for duration after once synchronizing. It uses lower communication overhead and establishes more robust synchronization situations for all nodes in the network. By periodical re-synchronization, the un-synchronization conditions such as nodes failures or topology change can be easily overcome. We implement our protocol in the Berkeley MICAz platform. The experimenting scenarios are 5-node and 18-node multi-hop topologies, and the re-synchronization periods are 30-second and 300-second. The experiment results show that the average synchronization errors of all nodes run with our protocol are ranged within several micro-seconds which are better than the previous protocol. [ABSTRACT FROM AUTHOR]

The activation of p38 mitogen-activated protein kinases (MAPKs) through a phosphorylation cascade is the canonical mode of regulation. Here, we report a novel activation mechanism for p38α. We show that Arg49 and Arg149 of p38α are methylated by protein arginine methyltransferase 1 (PRMT1). The non-methylation mutations of Lys49/Lys149 abolish the promotive effect of p38α on erythroid differentiation. MAPK kinase 3 (MKK3) is identified as the major p38α upstream kinase and MKK3-mediated activation of the R49/149K mutant p38α is greatly reduced. This is due to a profound reduction in the interaction of p38α and MKK3. PRMT1 can enhance both the methylation level of p38α and its interaction with MKK3. However, the phosphorylation of p38α by MKK3 is not a prerequisite for methylation. MAPK-activated protein kinase 2 (MAPKAPK2) is identified as a p38α downstream effector in the PRMT1-mediated promotion of erythroid differentiation. The interaction of MAPKAPK2 with p38α is also significantly reduced in the R49/149K mutant. Together, this study unveils a novel regulatory mechanism of p38α activation via protein arginine methylation on R49/R149 by PRMT1, which impacts partner interaction and thus promotes erythroid differentiation. This study provides a new insight into the complexity of the regulation of the versatile p38α signaling and suggests new directions in intervening p38α signaling.

Chicken essence (CE) is a liquid nutritional supplement made from cooking whole chickens. In traditional Chinese medicine, CE is used to support health, promote healing, increase metabolism, and relieve fatigue. However, few studies have examined the effect of CE on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CE on fatigue and ergogenic functions following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CE by oral gavage at 0, 845, 1690, or 4225 mg/kg/day for 4 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-related biomarkers serum lactate, ammonia, glucose, and creatine kinase (CK) after physical challenge. CE supplementation dose-dependently elevated endurance and grip strength. CE supplementation significantly decreased lactate, ammonia, and CK levels after physical challenge. Tissue glycogen content, an important energy source for exercise, was significantly increased with CE supplementation. In addition, CE supplementation had few subchronic toxic effects. The supplementation with CE can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.

Protein arginine methylation is emerging as a pivotal posttranslational modification involved in regulating various cellular processes; however, its role in erythropoiesis is still elusive. Erythropoiesis generates circulating red blood cells which are vital for body activity. Deficiency in erythroid differentiation causes anemia which compromises the quality of life. Despite extensive studies, the molecular events regulating erythropoiesis are not fully understood. This study showed that the increase in protein arginine methyltransferase 1 (PRMT1) levels, via transfection or protein transduction, significantly promoted erythroid differentiation in the bipotent human K562 cell line as well as in human primary hematopoietic progenitor CD34(+) cells. PRMT1 expression enhanced the production of hemoglobin and the erythroid surface marker glycophorin A, and also up-regulated several key transcription factors, GATA1, NF-E2 and EKLF, which are critical for lineage-specific differentiation. The shRNA-mediated knockdown of PRMT1 suppressed erythroid differentiation. The methyltransferase activity-deficient PRMT1G80R mutant failed to stimulate differentiation, indicating the requirement of arginine methylation of target proteins. Our results further showed that a specific isoform of p38 MAPK, p38α, promoted erythroid differentiation, whereas p38β did not play a role. The stimulation of erythroid differentiation by PRMT1 was diminished in p38α- but not p38β-knockdown cells. PRMT1 appeared to act upstream of p38α, since expression of p38α still promoted erythroid differentiation in PRMT1-knockdown cells, and expression of PRMT1 enhanced the activation of p38 MAPK. Importantly, we showed for the first time that PRMT1 was associated with p38α in cells by co-immunoprecipitation and that PRMT1 directly methylated p38α in in vitro methylation assays. Taken together, our findings unveil a link between PRMT1 and p38α in regulating the erythroid differentiation program and provide evidence suggesting a novel regulatory mechanism for p38α through arginine methylation.