Parental conflict driven regulation of endosperm cellularization by a family of Auxin Response Factors.

The endosperm is a reproductive tissue supporting embryo development. In most flowering plants, the initial divisions of endosperm nuclei are not succeeded by cellularization; this process occurs only after a specific number of mitotic cycles have taken place. The timing of cellularization significantly influences seed viability and size. Previous research implicated auxin as a key factor in initiating nuclear divisions and determining the timing of cellularization. Here we uncover the involvement of a family of clustered auxin response factors (cARFs) as dosage-sensitive regulators of endosperm cellularization. cARFs, maternally expressed and paternally silenced, are shown to induce cellularization, thereby restricting seed growth. Our findings align with the predictions of the parental conflict theory, suggesting that cARFs represent major molecular targets in this conflict. We further demonstrate a recurring amplification of cARFs in the Brassicaceae, suggesting an evolutionary response to parental conflict by reinforcing maternal control over endosperm cellularization. Our study highlights that antagonistic parental control on endosperm cellularization converges on auxin biosynthesis and signalling.

[Silent pulmonary shadows].

An elderly woman with a 1-year history of pulmonary shadows was admitted because of intermittent cough and sputum production for 2 months. Chest computed tomography (CT) scans showed bilateral consolidations and ground-glass opacities, with areas of low attenuation inside consolidative opacities on the mediastinal window. Previous history of radiotherapy for nasopharyngeal carcinoma and long-term use of a compound menthol nasal drops provided were important clues to the diagnosis. CT scan-guided needle lung biopsy and bronchoalveolar lavage were performed, and lipid-laden macrophages were confirmed in both bronchoalveolar lavage and lung tissue. Final diagnosis of exogenous lipoid pneumonia was made on the basis of her risk factors for aspiration, history of oil exposure, and classic radiological and histopathological features. Symptoms improved after discontinuation of causative exposure. It is important for clinicians to raise awareness of exogenous lipoid pneumonia and other aspiration lung diseases.

Association of Cognitive Reserve Indicator with Cognitive Decline and Structural Brain Differences in Middle and Older Age: Findings from the UK Biobank.

BACKGROUND: Cognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to dementia risk in late life. However, the association between CR and cognitive changes and brain imaging measures, especially in midlife, is unclear. OBJECTIVE: We aimed to explore the association of CR with cognitive decline and structural brain differences in middle and older age. DESIGN: This longitudinal study was from the UK Biobank project where participants completed baseline surveys between 2006 to 2010 and were followed (mean follow-up: 9 years). SETTING: A population-based study. PARTICIPANTS: A total of 42,301 dementia-free participants aged 40-70 were followed-up to detect cognitive changes. A subsample (n=34,041) underwent brain magnetic resonance imaging scans. MEASUREMENTS: We used latent class analysis to generate a CR indicator (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities. Cognitive tests for global and domain-specific cognition were administrated at baseline and follow-up. Total brain, white matter, grey matter, hippocampal, and white matter hyperintensity volumes (TBV, WMV, GMV, HV, and WMHV) were assessed at the follow-up examination. Data were analyzed using mixed-effects models and analysis of covariance. RESULTS: At baseline, 16,032 (37.9%), 10,709 (25.3%), and 15,560 (36.8%) participants had low, moderate, and high levels of CR, respectively. Compared with low CR, high CR was associated with slower declines in global cognition (ß [95% confidence interval]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). Participants with high CR had lower TBV, WMV, GMV, and WMHV, but higher HV when controlling for global cognition (corrected P <0.01 for all). The significant relationships between CR and cognition and TBV were present among both middle-aged (<60 years) and older (≥60 years) participants. The CR-cognition association remained significant despite reductions in brain structural properties. CONCLUSIONS: Higher CR is associated with slower cognitive decline, higher HV, and lower microvascular burden, especially in middle age. Individuals with high CR could tolerate smaller brain volumes while maintaining cognition. The benefit of CR for cognition is independent of structural brain differences. Our findings highlight the contribution of enhancing CR to helping compensate for neuroimaging alterations and ultimately prevent cognitive decline.

Anti-Hypertensive Drugs Moderate the Relationship of Blood Pressure with Alzheimer's Pathologies and Neurodegenerative Markers in Non-Demented Hypertensive Older Adults.

BACKGROUND: We aimed to explore whether the relationships of blood pressures (BPs) with Alzheimer's disease (AD) endophenotypes varied by usage of antihypertensive drugs (AHDs). METHODS: A total of 765 non-demented older adults (mean age: 74.4 years; female: 43.1%) with a self-reported history of hypertension were followed for 6 years. Multiple linear regression and linear-mixed effect models were used to investigate the interaction effects of five categories of AHDs (angiotensin-converting enzyme inhibitors [ACEI], angiotensin II receptor blockers [ARBs], ß-blocker, calcium channel blockers [CCB], diuretic) with BPs (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) on AD core pathology and neurodegenerative markers. RESULTS: After Bonferroni correction, significant interaction effects of BPs with AHDs were observed. Elevated SBP or PP in late-life was associated with higher levels of cerebral Aß burden (diuretic alone/ß-blocker × SBP), higher levels of CSF tau proteins (diuretic × SBP/PP, ARBs/CCB × SBP), and lower volume of entorhinal region (ß-blocker × SBP, diuretic × PP) only among hypertensive patients who received no anti-hypertensive treatments, while these associations became compromised or null for users of specific AHDs except for ACEI. Compared to taking other classes of AHDs, elevated SBP in late-life was associated with lower cerebral Aß burden in diuretic users (padjusted = 0.08) and was associated with higher CSF tau proteins in ACEI alone users (padjusted = 0.03). Longitudinal data validated the above-mentioned interaction effects on changes of cerebral Aß burden (padjusted < 0.05), CSF tau proteins (padjusted < 0.10), and brain atrophy (padjusted < 0.05). CONCLUSIONS: The relationships of late-life BP with AD pathology and neurodegeneration could be modified by anti-hypertensive treatments and varied by AHD classification. These findings provide preliminary evidence for tailored BP management strategy for preventing AD among late-life hypertensive adults.

Assessing Spns2-dependent S1P Transport as a Prospective Therapeutic Target.

S1P (sphingosine 1-phosphate) receptor modulator (SRM) drugs interfere with lymphocyte trafficking by downregulating lymphocyte S1P receptors. While the immunosuppressive activity of SRM drugs has proved useful in treating autoimmune diseases such as multiple sclerosis, that drug class is beset by on-target liabilities such as initial dose bradycardia. The S1P that binds to cell surface lymphocyte S1P receptors is provided by S1P transporters. Mice born deficient in one of these, spinster homolog 2 (Spns2), are lymphocytopenic and have low lymph S1P concentrations. Such observations suggest that inhibition of Spns2-mediated S1P transport might provide another therapeutically beneficial method to modulate immune cell positioning. We report here results using a novel S1P transport blocker (STB), SLF80821178, to investigate the consequences of S1P transport inhibition in rodents. We found that SLF80821178 is efficacious in a multiple sclerosis model but - unlike the SRM fingolimod - neither decreases heart rate nor compromises lung endothelial barrier function. Notably, although Spns2 null mice have a sensorineural hearing defect, mice treated chronically with SLF80821178 have normal hearing acuity. STBs such as SLF80821178 evoke a dose-dependent decrease in peripheral blood lymphocyte counts, which affords a reliable pharmacodynamic marker of target engagement. However, the maximal reduction in circulating lymphocyte counts in response to SLF80821178 is substantially less than the response to SRMs such as fingolimod (50% vs. 90%) due to a lesser effect on T lymphocyte sub-populations by SLF80821178. Finally, in contrast to results obtained with Spns2 deficient mice, lymph S1P concentrations were not significantly changed in response to administration of STBs at doses that evoke maximal lymphopenia, which indicates that current understanding of the mechanism of action of S1P transport inhibitors is incomplete.

[Clinical characteristics and efficacy of vocal fold epidermoid cysts coexisting with sulcus vocalis].

Objective: To investigate the clinical characteristics and voice outcomes after laryngeal microsurgery for vocal fold epidermoid cysts coexisting with sulcus vocalis. Methods: The clinical data of 115 vocal fold epidermoid cysts coexisting with sulcus vocalis patients in Shandong provincial ENT hospital, were retrospectively analyzed, including 49 males and 66 females, aged 17-70 years old, and the duration of hoarseness ranged from 6 months to 30 years. All patients underwent surgery through suspension laryngoscope and microscope under general anestgesia. Ninety-four patients were treated with microflap excision of sulcus vocalis, cyst wall, and contents.And 21 patients that occulted with mucosal bridges were applied mucosal bridges resection (2 cases) and mucosal bridges reconstruction (19 cases) respectively. Videolaryngoscopy, subjective voice evaluation (GRBAS), objective voice evaluation, and Voice Handicap Index(VHI) were performed before and after surgery. All patients underwent histopathologic examination and follow-up after the procedure. The preoperative acoustic parameters of patients with vocal fold epidermoid cysts coexisting with sulcus vocalis were compared with those of vocal fold mucus retention cysts and simple vocal fold epidermoid cysts by independent samples t-test. The patients were compared by paired t-test for preoperative and postoperative parameters. Results: Significant reduction or lack of mucosal waves were shown via videolaryngostroboscopy in all 115 cases.In addition, vascular changes including dilation, tortuousness, increased branches, and abrupt direction change were shown on the cystic area. Eighty-one patients were detected cysts and/or sulcus vocalis by preoperative laryngoscopy, and intraoperative microscopic findings in the remaining 34 patients. The intraoperative microscopic examination revealed a focal pouch-like deficit plunging into the vocal ligament or muscle. The deep surface of the mucosal bridges was sulcus vocalis, and that in 89 cysts was lined with caseous content. Histopathology demonstrated a cystic cavity structure lined with squamous epithelium and caseous keratin desquamation inside the cystic cavity. Four of 115 patients were lost at follow-up and excluded from the analysis of voice outcomes after surgery. There was no significant mucosal wave and the voice quality in all but 14 patients 1month after surgery. Except for the fundamental frequency and noise harmonic ratio, all other voice parameters[ G, R, B, A, VHI-10, jitter, shimmer, maximum phonatory time (MPT) ]showed a significant improvement 3 months after surgery(t=15.82, 20.82, 17.61, 7.30, 38.88, 7.84, 5.88, -6.26, respectively, P<0.05). Then mucosal waves and the voice quality were gradually improved and became steady in 6 months after surgery. The subjective and objective voice parameters[G, R, B, A, VHI-10, jitter, shimmer, noise to harmonic ratio(NHR), MPT], except for the fundamental frequency, were all significantly improved(t=23.47, 25.79, 18.37, 9.84, 54.45, 10.68, 8.07, 3.24, -9.08, respectively, P<0.05). In addition, there were 2 patients with no significant improvement after the operation. Steady function with no complications was observed during the 12 months (up to 3 years in 34 patients) follow-up period in 111 patients. Conclusion: Ruptured vocal fold epidermoid cysts can result in sulcus vocalis and mucosal bridges. Characteristics changes in preoperative videolaryngoscopy are effective diagnostic tools. The complete excision of the cyst wall and repair of the lamina propria can lead to satisfactory long-term effects.

[Efficacy and safety analysis of P-GemDOx regimen and stratified prognosis in patients with early extranodal NK/T cell lymphoma].

Objective: To assess the efficacy, safety, and related prognostic factors associated with the P-GemDOx regimen as a first-line treatment for patients with early-stage extranodal natural killer (NK) /T cell lymphoma (ENKTL) . Methods: A retrospective analysis was performed on sixty early-stage ENKTL patients treated with the P-GemDOx regimen who were admitted to the First Affiliated Hospital of Nanjing Medical University between August 2015 and May 2021. The Chi-square test or Fisher's exact test was used to compare group differences, and the Log-rank test was used to compare the differences in survival. Survival outcomes and prognostic factors were examined. Results: After completing 4 to 6 cycles of P-GemDOx chemotherapy, the overall response rate (ORR) was 88.3%, with forty-six patients (76.7% ) achieving complete response (CR). The 4-year progression-free survival (PFS) and overall survival (OS) rates were (66.3±7.1) % and (79.5±6.0) %, respectively. According to the PINK/PINK-E model, there was no significant difference in survival outcomes among risk groups. 23.3% of patients experienced progression of disease within 24 months (POD<24). OS estimates differed significantly (P<0.001) between the POD<24 group (n=14) and the POD≥24 group (n=46). Analysis showed that SUVmax > 12.8 at diagnosis, non-single nasal cavity infiltration, and response less than CR after 4-6 cycles all had a significant association with POD24. We used these data as the basis for predicting POD<24 international prognostic index (POD24-IPI). Patients were stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high risk (two or three risk factors). These groups were associated with 4-year OS rate of 100%, (85.6±9.7) %, and (65.0±10.2) %, respectively (P=0.014). The P-GemDOx regimen was well tolerated, with hematological toxicity being the main side effect. Conclusion: This study demonstrated that the P-GemDOx regimen is effective and safe in the first-line treatment of early-stage ENKTL, and POD24-IPI is a promising prognostic model.

Evidence for Chiral Wobbler in Nuclei.

Three ΔI=1 bands with the πg_{9/2}⊗νg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.

[Tea polyphenols ameliorates acute lung injury in septic mice by inhibiting NLRP3 inflammasomes].

OBJECTIVE: To investigate the mechanism of tea polyphenols (TP) for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice. METHODS: Sixty C57BL/6 mice were randomly assigned into sham-operated, cecal ligation and puncture (CLP) and CLP +TP treatment groups, and survival of the mice was recorded after modeling in each group. The lung wet/dry weight ratio and myeloperoxidase (MPO) activity were determined, and lung injury of the mice was evaluated using HE staining and acute lung injury score. The expressions of IL-1ß, TNF-α, IL-6, NLRP3, caspase-1 p10, ASC, MPO, and caspase-8 in the lung tissue were detected using ELISA, Western blotting, or immunohistochemical staining. MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress. Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4. RESULTS: The postoperative mortality rate at 72 h, lung wet/dry weight ratio, MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group (P < 0.05). Treatment with TP significantly reduced the expressions of NLRP3-related inflammatory factors (P < 0.05) and lowered MDA and H2O2 levels in the lung tissue of the septic mice (P < 0.05). Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group. CONCLUSION: TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

Effect of PI3K/AKT/HIF-1α signaling pathway on oxidative stress and apoptosis in nucleus pulposus cells.

OBJECTIVE: The aim of the study was to explore the expression of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT)/hypoxia-induced factor-1 alpha (HIF-1α) signaling pathway and the apoptosis of nucleus pulposus cells (NPCs) under different oxygen concentrations to clarify the biological characteristics of NPCs and the molecular mechanism of intervertebral disc degeneration (IVDD). MATERIALS AND METHODS: Normal and degenerated human NPCs were collected. Leibovitz's medium with 100 µmol/L CoCl2 was used to establish a hypoxic culture environment, and 100 µmol/L H2O2 was used to establish an oxidative stress culture environment. Third-generation NPCs were divided into 6 groups: normal NPCs + hypoxia, normal NPCs + normoxia, normal NPCs + oxidative stress, degenerated NPCs + hypoxia, degenerated NPCs + normoxia, and degenerated NPCs + oxidative stress. Normal NPCs + hypoxia was used as the experimental control group. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) method. Cell apoptosis rate was assessed by flow cytometry, and expression levels of PI3K, AKT, and HIF-1α were determined by Real-Time-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: The cell proliferation rate of both normal and degenerated NPCs decreased with increasing oxygen concentration. Conversely, the apoptosis rate increased as the oxygen concentration increased (p<0.05). Compared with the control group, whether the cells degenerated had a very significant impact on the apoptosis rate (p<0.001), and oxygen concentration also had a highly significant impact on both the cell proliferation rate and apoptosis rate (both p<0.001). The interaction between cell degeneration and oxygen concentration significantly affected both cell proliferation and apoptosis rates (p<0.05). Considering the expression levels of PI3K, AKT, and HIF-1α, normal NPCs had the highest levels under low oxygen concentrations, followed by oxidative stress and normoxia. In degenerated NPCs, the expression levels also decrease as the oxygen concentration increases. CONCLUSIONS: The PI3K/Akt/HIF-1α signaling pathway plays a significant role in inhibiting oxidative stress, antagonizing NPC apoptosis, and consequently delaying IVDD.

[Clinicopathological analysis of adult hepatic mesenchymal hamartoma].

Objective: To explore the clinicopathological and molecular genetic features of adult hepatic mesenchymal hamartoma (MHL). Methods: A total of five confirmed adult MHL cases diagnosed at the Pathology Department of the First Medical Center of the People's Liberation Army General Hospital between 2009 and 2022 were collected. Histomorphological observation and immunohistochemical staining were conducted. Gene detection was performed by next-generation sequencing. Results: Among the five cases, four were male and one was female, aged 46-67 years, with an average age of 56.2 years. The maximum diameter was 5.3-13.5cm, and the average diameter was 9.2cm. Tumors were generally cystic, solid, or mixed cystic-solid. Histopathologically, in four out of five cases of MHL, malignant transformation occurred, of which three cases were malignantly transformed into undifferentiated embryonal sarcoma and one case was malignantly transformed into a malignant solitary fibrous tumor. NAB2-STAT6 gene rearrangements were identified. Conclusion: Adult MHL is a rare kind of tumor with malignant potential, and it is difficult to diagnose with preoperative imaging examinations. A fine-needle biopsy is rarely used for diagnosis, but surgical resection of symptomatic or enlarged lesions is recommended to rule out the possibility of malignancy and further diagnosis. Genetic testing results revealed the complex genetic alterations in MHL, and it was found that adult MHL can malignantly transform into malignant solitary fibrous tumors. We believe that genome-wide analysis is necessary to determine the unique molecular characteristics of MHL and identify potential targets for therapeutic intervention.

[Comparison of the impact of orthodontic treatment on pulp volume in adolescents and adults].

Objective: To compare the impact of orthodontic treatment on pulp volume in adolescents and adults. Methods: Cone-beam CT data of 62 patients undergoing orthodontic treatment at the Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, from January 2019 to March 2022 were collected. Patients were divided into two age groups (31 patients in each group): adolescent group (aged 13-17, 17 males and 14 females) and adult group (aged 21-25, 12 males and 19 females). Pre-and post-treatment reconstructions of the pulp and dental tissues of upper first molars (UM1) and lower central incisors (L1) were performed. Measurements included pulp volume for UM1 (UM1 P) and L1 (L1 P), pulp chamber volume (UM1 PC) and root canal volume (UM1 RC) for UM1, root length for L1 (L1 RL), and mesiobuccal root length for UM1 (UM1 RL), as well as chamber heights at specific landmarks [the lengths from the central fossa fusion site to the roof of the pulp chamber (H1), the floor of the pulp chamber (H2), the nearest point of root divergence as well as crown-root bifurcation (H3), the farthest point of root divergence (H4), and the pulp chamber height (H5)] in UM1. Changes in these indices were calculated and analyzed using paired and independent sample t-tests for within-group and between-group differences, respectively. Pearson correlation was used to assess potential associations among H5, root length, and pulp volume changes. Results: Before and after orthodontic treatment, no significant difference was observed in the adult group for L1 P (t=-0.03, P=0.975), while significant differences were noted for UM1 P, UM1 PC, and UM1 RC (t=9.98, P<0.001; t=9.04, P<0.001; t=6.69, P<0.001). In the adolescent group, significant differences were found for both L1 P and UM1 P (t=2.25, P=0.029; t=6.30, P<0.001). After orthodontic treatment, the absolute value changes of UM1 P, UM1 PC, and L1 P in the adolescent group were (19.75±9.58), (15.07±7.65) and (1.89±6.29) mm3, respectively, and in the adult group were (13.33±9.41), (9.16±7.05) and (0.02±4.66) mm3, respectively (t=3.77, P<0.001; t=4.48, P<0.001; t=2.34, P=0.048). There was no significant absolute difference in the amount of UM1 RC between the two groups after orthodontic treatment (t=0.86, P=0.391). Before and after orthodontic treatment, the absolute value changes of L1 RL, H1 and H5 in the adolescent group were (0.54±0.41), (0.38±0.27) and (0.71±0.33) mm, respectively, and the absolute value changes in the adult group were (0.78±0.62), (0.26±0.20) and (0.57±0.28) mm, respectively (t=-2.43, P=0.017; t=2.96, P=0.004; t=2.57, P=0.011). Whereas no significant differences were observed for UM1 RL, H2, H3, and H4 (t=-0.85, P=0.400; t=0.43, P=0.669; t=-0.50, P=0.619; t=1.46, P=0.148). Additionally, significant correlations were found between changes in H5 and UM1 RL with UM1 P (r=0.35, P<0.001; r=0.19, P=0.030), but not between Changes in L1 RL and L1 P (r=0.11, P>0.05). Conclusions: The effect of orthodontic treatment on pulp volume in adolescents and adults were different.

[Analysis of the correlative factors of long-term positive nucleic acid and the characteristics of nucleic acid conversion in novel coronavirus infected patients].

To analyze the correlative factors of long-term positive nucleic acid and the characteristics of negative nucleic acid conversion in novel coronavirus infected patients.Novel coronavirus infected patients who were hospitalized in Beijing Tsinghua Changgung Hospital from December 2022 to June 2023 were retrospectively included. Patients who were positive for novel coronavirus nucleic acid for ≥30 days were selected as the long-positive group, and age-and sex-matched patients with novel coronavirus nucleic acid for <30 days were selected as the control group. The clinical data of all enrolled patients were collected. Binary logistic regression was used to analyze the influencing factors of the positive duration of nucleic acid ≥30 days. The Cox risk ratio model was used to analyze the risk factors for the prognosis of severe patients during hospitalization, and the difference in the time of nucleic acid conversion between the upper and lower respiratory tract was compared between the groups. A total of 30 patients were included in the long-positive group, including 24 males and 6 females, aged [M (Q1, Q3)] 77 (64, 86) years. Fifty-eight patients were included in the control group, including 46 males and 12 females, aged 78 (66, 86) years. Transplantation status (OR=50.32, 95%CI: 1.98-1 278.63, P=0.018), malignant tumor (OR=12.85, 95%CI: 1.65-99.88, P=0.015), CD4+T cell count (OR=0.99, 95%CI: 0.99-1.00, P=0.005) were correlative factors for positive nucleic acid≥30 days. Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score (HR=1.12, 95%CI: 1.03-1.22, P=0.012) and nucleic acid positive time (HR=1.16, 95%CI: 1.01-1.33, P=0.031) were correlative factors for death in severe patients. The nucleic acid conversion time of the lower respiratory tract specimens in both groups was later than that of the upper respiratory tract specimens (all P<0.001). Weakened underlying immunity is a correlative factor for long-term novel coronavirus nucleic acid positivity, and long-term positive novel coronavirus nucleic acid in severe patients indicates high risk of death. The nucleic acid of the lower respiratory tract specimen turned negative later than the upper respiratory tract specimen.

Plasma and milk metabolomics revealed changes in amino acid metabolism in Holstein dairy cows under heat stress.

Our understanding of metabolic alterations triggered by heat stress is incomplete, which limits the designing of nutritional strategies to mitigate negative productive and health effects. Thus, this study aimed to explore the metabolic responses of heat-stressed dairy cows to dietary supplementation with vitamin D3/Ca and vitamin E/Se. Twelve multiparous Holstein cows were enrolled in a split-plot Latin square design with two distinct vitamin E/Se supplementation levels, either at a low (ESe-, n = 6, 11.1 IU/kg vitamin E and 0.55 mg/kg Se) or a high dose (ESe+, n = 6 223 IU/kg vitamin E and 1.8 mg/kg Se) as the main plot. Treatment subplots, arranged in a replicated 3 × 3 Latin square design, comprised heat challenge (Temperature Humidity Index, THI: 72.0-82.0) supplemented with different levels of vitamin D3/Ca: either low (HS/DCa-, 1 012 IU/kg and 0.73%, respectively) or high (HS/DCa+, 3 764 IU/kg and 0.97%, respectively), and a pair-fed control group in thermoneutrality (THI = 61.0-64.0) receiving the low dose of vitamin D3/Ca (TN). The liquid chromatography-mass spectrometry-based metabolome profile was determined in blood plasma and milk sampled at the beginning (day 0) and end (day 14) of each experimental period. The results were analyzed for the effect of (1) TN vs. HS/ESe-/DCa-, and (2) the vitamin E/Se and vitamin D3/Ca supplementation. No group or group × day effects were detected in the plasma metabolome (false discovery rate, FDR > 0.05), except for triglyceride 52:2 being higher (FDR = 0.03) on day 0 than 14. Taurine, creatinine and butyryl-carnitine showed group × day interactions in the milk metabolome (FDR ≤ 0.05) as creatinine (+22%) and butyryl-carnitine (+190%) were increased (P < 0.01) on day 14, and taurine was decreased (-65%, P < 0.01) on day 14 in the heat stress (HS) cows, compared with day 0. Most compounds were unaffected by vitamin E/Se or vitamin D3/Ca supplementation level or their interaction (FDR > 0.05) in plasma and milk, except for milk alanine which was lower (-69%, FDR = 0.03) in the E/Se+ groups, compared with E/Se-. Our results indicated that HS triggered more prominent changes in the milk than in the plasma metabolome, with consistent results in milk suggesting increased muscle catabolism, as reflected by increased creatinine, alanine and citrulline levels. Supplementing with high levels of vitamin E/Se or vitamin D3/Ca or their combination did not appear to affect the metabolic remodeling triggered by HS.

Relationships of Hypnotics with Incident Dementia and Alzheimer's Disease: A Longitudinal Study and Meta-Analysis.

BACKGROUND: Evidence describing the association between hypnotics use and dementia risk is conflicting. It is unknown if the controversy is related to the type or dose of hypnotics or if hypnotics affect different populations. OBJECTIVES: We sought to derive lessons learned and future projections based on evidence from longitudinal studies. MEASUREMENTS: In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, 1,543 older adults without dementia (mean age = 73.3 years, female = 45%) were followed for four years. The association between hypnotics and the risk of Alzheimer's disease (AD) was investigated using Cox proportional hazards regressions. Next, electronic databases were searched until March 2022 to conduct the evidence synthesis of the associations of hypnotics with incident risk of dementia. RESULTS: In the ADNI cohort, ever use of hypnotics was associated with an increased risk of AD (hazard ratio = 1.96, 95% confidence intervals = 1.23-3.11, p < 0.01). This association was significant for benzodiazepines and Z-drugs but not for melatonin. The association was stronger in long-term (more than one year) users and those with high cumulative doses. A meta-analysis of 26 longitudinal studies with 3,942,018 participants revealed a correlation between the use of hypnotics and the risk of dementia (relative risk = 1.23, 95% confidence intervals = 1.13-1.33, p < 0.001, median risk difference = 4%). It is a linear dose-response relationship, if a person takes the daily recommended dose for 100 days, their risk of developing dementia increases by 5% relative to non-users. According to subgroup analyses, neither association was significant among patients with a history of insomnia. CONCLUSIONS: Individuals who use hypnotics, especially high-dose or long-term users, are at a higher risk of dementia and AD. The main issue with conclusion credibility is heterogeneity.

High-speed multihull anti-pitching control based on heave velocity and pitch angular velocity estimation.

This paper proposes a novel anti-pitching control algorithm based on algebraic model predictive control (AMPC) for high-speed multihull, in which the heave velocity and pitch angular velocity cannot be measured directly. Specifically, a multihull vertical control model is established with the employed anti-pitching appendages, and the uncertainty of the model as well as the coupling between heave and pitch motion are investigated. To address unmeasurable of the heave velocity and pitch angular velocity, a novel kinematics-based Kalman filter is designed to estimate these states online, which is substantially different from the existing works. Then, the AMPC strategy for varying receding-horizon optimization is proposed, which significantly reduces the amount of online calculation. To estimate the lumped uncertainty, the second-order filter data of input and output is used to design a disturbance observer with less parameters, which can perform feed-forward compensation to enhance the robustness. The convergence of the disturbance observer and the closed-loop system is analyzed mathematically. Finally, the advantages of the proposed anti-pitching control approach are demonstrated in both theory and simulation.

Acupuncture and its ability to restore and maintain immune homeostasis.

Immune homeostasis is a steady immune state that not only protects the host from pathogens but also prevents the emergence of pathological self-reactive immune cells. The disruption of immune homeostasis leads to the development of various diseases, such as cancer and autoimmune diseases. An emerging paradigm for the treatment of these diseases with dysfunctional immune systems is the restoration and maintenance of immune homeostasis. However, currently available drugs exert a unidirectional influence on immunity whereby they either augment or inhibit it. This strategy is associated with the drawback of potential adverse effects arising from uncontrolled activation or suppression of the immune system. Fortunately, evidence suggests that acupuncture can bidirectionally regulate the immune system to maintain immune homeostasis. In cases of immunosuppressive diseases (e.g. cancer), acupuncture has an enhancing effect on immunity. Conversely, in autoimmune diseases (e.g. rheumatoid arthritis), acupuncture has been observed to have an immunosuppressive effect, which helps restore normal immune tolerance. However, there is no publication systematically summarizing the bidirectional regulatory effects of acupuncture on the immune system in the literature. Here, our review provides a comprehensive overview of the various mechanisms through which acupuncture modulates the immune system in a bidirectional manner. These mechanisms include the augmentation of NK and CD8+ T cell function, as well as the restoration of Th1/Th2, Th17/Treg and M1/M2 balance. Thus, we propose the concept that acupuncture has the potential to alleviate illnesses through the facilitation of immune normalization. Moreover, we further highlight the therapeutic potential of acupuncture.