Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.

Comparative analysis of reduced toxicity conditioning regimens between fludarabine plus melphalan and fludarabine plus busulfex in adult patients with acute lymphoblastic leukemia.

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

Exploring empathic engagement in immersive media: An EEG study on mu rhythm suppression in VR.

This study investigates the influence of immersive media, particularly Virtual Reality (VR), on empathic responses, in comparison to traditional television (TV), using electroencephalography (EEG). We employed mu rhythm suppression as a measurable neural marker to gauge empathic engagement, as its increase generally signifies heightened empathic responses. Our findings exhibit a greater mu rhythm suppression in VR conditions compared to TV conditions, suggesting a potential enhancement in empathic responses with VR. Furthermore, our results revealed that the strength of empathic responses was not confined to specific actions depicted in the video clips, underscoring the possibility of broader implications. This research contributes to the ongoing discourse on the effects of different media environments on empathic engagement, particularly emphasizing the unique role of immersive technologies such as VR. It invites further investigation into how such technologies can shape and potentially enhance the empathic experience.

Microplastic accumulation dynamics in Han river headwaters: Sediment interactions and environmental implication.

The prevalence of microplastic (MP) contamination has become a significant environmental concern due to its pervasive nature and persistent effects. While sediments are considered major repositories for MPs, information on their spatial distribution within these matrices is insufficient. This research examined both the horizontal and vertical presence of MPs in the sediments surrounding Lake Paldang in South Korea, alongside a comprehensive evaluation of the physicochemical characteristics of the samples obtained. The total content of MPs varied from 2.15 to 122.2 particles g-1. The average contents of MPs on surface sediments were 40.47, 34.14, 5.01, and 8.19 particles g-1 in north mainstream (NM), south mainstream (SM), tributary (TB), and Tributary catchment (TC) based on Sonae Island, Gyeongan stream, respectively. The most abundant MP types were polyethylene (PE), polytetrafluoroethylene (PTFE), and polypropylene (PP), accounting for more than 70% of the total MPs. The most abundant sizes of MPs were within 45-100 µm. At all sediment depths, polymers were distributed in the order PE, PP, and polyester in NM, SM, and TC, respectively, whereas PTFE mainly occurred in the surface layer. MPs distribution also exhibited seasonal variation as larger inflows and flow rates varied with season.

Role of Portosystemic Shunt and Portal Vein Stent in Managing Portal Hypertension Due to Hematological Diseases.

INTRODUCTION: Patients with hematological diseases experience complications related to portal hypertension, including life-threatening complications such as variceal bleeding. METHODS: We analyzed the prognosis of patients with hematological diseases and portal hypertension treated with transjugular intrahepatic portosystemic shunts (TIPS) or portal vein stents. We retrospectively assessed patients with hematological diseases and portal hypertension who had variceal bleeding. We evaluated the characteristics and prognosis of the enrolled patients. A total of 11 patients with hematological diseases who underwent TIPS, or portal vein stenting, were evaluated. RESULTS: The median follow-up period was 420 days. Of the 11 patients, eight showed resolution of portal hypertension and its complications following TIPS, or stent insertion. One patient experienced rebleeding due to incomplete resolution of portal hypertension, and two other patients also experienced rebleeding because they underwent TIPS closure or revision due to repetitive hepatic encephalopathy. CONCLUSION: Portosystemic shunt and stent installation are effective treatment options for portal hypertension due to hematological diseases.

Analytical Performance Evaluation of a Digital Real-Time PCR for Quantifying Major BCR::ABL1 Transcripts.

BACKGROUND: Accurate quantification of the BCR::ABL1 transcripts is essential for measurable residual disease (MRD) monitoring in chronic myeloid leukemia (CML) after tyrosine kinase inhibitor (TKI) treatment. This study evaluated the newly developed digital real-time PCR method, Dr. PCR, as an alternative reverse transcription-PCR (qRT-PCR) for MRD detection. METHODS: The performance of Dr. PCR was assessed using reference and clinical materials. Precision, linearity, and correlation with qRT-PCR were evaluated. MRD levels detected by Dr. PCR were compared with qRT-PCR, and practical advantages were investigated. RESULTS: Dr. PCR detected MRD up to 0.0032%IS (MR4.5) with excellent precision and linearity and showed a strong correlation with qRT-PCR results. Notably, Dr. PCR identified higher levels of MRD in 12.7% (29/229) of patients than qRT-PCR, including six cases of MR4, which is a critical level for TKI discontinuation. Dr. PCR also allowed for sufficient ABL1 copies in all cases, while qRT-PCR necessitated multiple repeat tests in 3.5% (8/229) of cases. CONCLUSION: Our study provides a body of evidence supporting the clinical application of Dr. PCR as a rapid and efficient method for assessing MRD in patients with CML under the current treatment regimen.

Reduced toxicity (FluBu3) versus myeloablative (BuCy) conditioning in acute myeloid leukemia patients who received first allogeneic hematopoietic stem cell transplantation in measurable residual disease-negative CR1.

In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.

OsbZIP38/87-mediated activation of OsHXK7 improves the viability of rice cells under hypoxic conditions.

Maintenance of energy metabolism is critical for rice (Oryza sativa) tolerance under submerged cultivation. Here, OsHXK7 was the most actively induced hexokinase gene in the embryos of hypoxically germinating rice seeds. Suspension-cultured cells established from seeds of T-DNA null mutants for the OsHXK7 locus did not regrow after 3-d-hypoxic stress and showed increased susceptibility to low-oxygen stress-in terms of viability-and decreased alcoholic fermentation activities compared to those of the wild-type. The promoter element containing the TGACG-motif, a well-known target site for the basic leucine zipper (bZIP) transcription factors, was responsible for sugar regulation of the OsHXK7 promoter activity. Systematic screening of the OsbZIP genes showing the similar expression patterns to that of OsHXK7 in the transcriptomic datasets produced two bZIP genes, OsbZIP38 and 87, belonging to the S1 bZIP subfamily as the candidate for the activator for this gene expression. Gain- and loss-of-function experiments through transient expression assays have demonstrated that these two bZIP proteins are indeed involved in the induction of OsHXK7 expression under starvation or low-energy conditions. Our finding suggests that C/S1 bZIP network-mediated hypoxic deregulation of sugar-responsive genes may work in concert for the molecular adaptation of rice cells to submergence.

Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients.

BACKGROUND: Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. METHODS: The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. RESULTS: The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83-21.47, P = 0.003). Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. CONCLUSION: These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Identification of protein related to dietary vitamin B3 deficiency in Mediterranean fruit fly larvae.

Mediterranean fruit fly (medfly), Ceratitis capitata, is among the most destructive agricultural pest. The sterile insect technique (SIT) can effectively control medfly populations. To rear healthy medflies for the purpose of SIT, it is essential to supplement B vitamins in the diet. However, the function of the dietary B vitamins in C. capitata larvae is not known. With the microscopic analysis, several organs in the head were examined and the spiracle formation and sensory organs were normally formed between the niacin-supplied and niacin-absent groups. However, formation of the ocular depression was differently developed between the two groups, although the hypostomal sclerite was formed properly. These results signify that niacin deficiency maybe interrupt development of medfly larvae ocular depression. Proteomic analyses using LC MS/MS detected a total of 1845 proteins in two flies. A total of 607 of the 1845 proteins were overexpressed and one third (598 proteins) were downexpressed in the niacin-deficient larvae, while about one third were similarly expressed. Overexpressed proteins in the niacin-deficient larvae included ryanodine receptor 44 F, intergrin-PS, spalt-major homeotic protein, and chiffon protein. One of important overexpressed proteins was optomotor-blind protein in relation to wing development in the niacin-deficient medfly larvae.