Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb.

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected.

Paradoxical Mitophagy Regulation by PINK1 and TUFm.

Aberrant mitophagy has been implicated in a broad spectrum of disorders. PINK1, Parkin, and ubiquitin have pivotal roles in priming mitophagy. However, the entire regulatory landscape and the precise control mechanisms of mitophagy remain to be elucidated. Here, we uncover fundamental mitophagy regulation involving PINK1 and a non-canonical role of the mitochondrial Tu translation elongation factor (TUFm). The mitochondrion-cytosol dual-localized TUFm interacts with PINK1 biochemically and genetically, which is an evolutionarily conserved Parkin-independent route toward mitophagy. A PINK1-dependent TUFm phosphoswitch at Ser222 determines conversion from activating to suppressing mitophagy. PINK1 modulates differential translocation of TUFm because p-S222-TUFm is restricted predominantly to the cytosol, where it inhibits mitophagy by impeding Atg5-Atg12 formation. The self-antagonizing feature of PINK1/TUFm is critical for the robustness of mitophagy regulation, achieved by the unique kinetic parameters of p-S222-TUFm, p-S65-ubiquitin, and their common kinase PINK1. Our findings provide new mechanistic insights into mitophagy and mitophagy-associated disorders.

BOTRYOID POLLEN 1 regulates ROS-triggered PCD and pollen wall development by controlling UDP-sugar homeostasis in rice.

Uridine diphosphate (UDP)-sugars are important metabolites involved in the biosynthesis of polysaccharides and may be important signaling molecules. UDP-glucose 4-epimerase (UGE) catalyzes the interconversion between UDP-Glc and UDP-Gal, whose biological function in rice (Oryza sativa) fertility is poorly understood. Here, we identify and characterize the botryoid pollen 1 (bp1) mutant and show that BP1 encodes a UGE that regulates UDP-sugar homeostasis, thereby controlling the development of rice anthers. The loss of BP1 function led to massive accumulation of UDP-Glc and imbalance of other UDP-sugars. We determined that the higher levels of UDP-Glc and its derivatives in bp1 may induce the expression of NADPH oxidase genes, resulting in a premature accumulation of reactive oxygen species (ROS), thereby advancing programmed cell death (PCD) of anther walls but delaying the end of tapetal degradation. The accumulation of UDP-Glc as metabolites resulted in an abnormal degradation of callose, producing an adhesive microspore. Furthermore, the UDP-sugar metabolism pathway is not only involved in the formation of intine but also in the formation of the initial framework for extine. Our results reveal how UDP-sugars regulate anther development and provide new clues for cellular ROS accumulation and PCD triggered by UDP-Glc as a signaling molecule.

Dynamic Gardner cross-over in a simple glass.

The criticality of the jamming transition responsible for amorphous solidification has been theoretically linked to the marginal stability of a thermodynamic Gardner phase. While the critical exponents of jamming appear independent of the preparation history, the pertinence of Gardner physics far from equilibrium is an open question. To fill this gap, we numerically study the nonequilibrium dynamics of hard disks compressed toward the jamming transition using a broad variety of protocols. We show that dynamic signatures of Gardner physics can be disentangled from the aging relaxation dynamics. We thus define a generic dynamic Gardner cross-over regardless of the history. Our results show that the jamming transition is always accessed by exploring increasingly complex landscape, resulting in anomalous microscopic relaxation dynamics that remains to be understood theoretically.

Two C-terminal isoforms of Aplysia tachykinin-related peptide receptors exhibit phosphorylation-dependent and independent desensitization mechanisms.

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin (TK) signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their post-translational modifications were observed in extracts of CNS ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (TKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C-termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

The OsMYC2-JA feedback loop regulates diurnal flower-opening time via cell wall loosening in rice.

Diurnal flower-opening time (DFOT), the time of spikelet opening during the day, is an important trait for hybrid rice (Oryza sativa L.) seed production. Hybrids between indica and japonica rice varieties have strong heterosis, but the parental lines usually have different, nonoverlapping DFOTs. This reduces the success of hybrid seed production in crosses between indica and japonica subspecies, thus hindering the utilization of indica and japonica inter-subspecies heterosis. However, little is known about the molecular mechanisms regulating DFOT in rice. Here, we obtained japonica rice lines with a DFOT 1.5 h earlier than the wild type by overexpressing OsMYC2, a gene encoding a key transcription factor in the jasmonate (JA) signaling pathway. OsMYC2 is activated by JA signaling and directly regulates the transcription of genes related to JA biosynthesis and cell wall metabolism. Overexpressing OsMYC2 led to significantly increased JA contents and decreased cellulose and hemicellulose contents in lodicule cells, as well as the softening of lodicule cell walls. This may facilitate the swelling of lodicules, resulting in early diurnal flower-opening. These results suggest that the OsMYC2-JA feedback loop regulates DFOT in rice via cell wall remodeling. These findings shed light on the understanding of regulatory mechanism of the DFOT of plants, which should promote the development of indica and japonica varieties suitable for hybrid rice breeding.

Olfactory regulation by dopamine and DRD2 receptor in the nose.

SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain relatively unexplored. Here we show that dopamine D2 receptor (DRD2) is expressed in the cilia and somata of mature olfactory sensory neurons (OSNs), while nasal dopamine (DA) is mainly released from the sympathetic nerve terminals, which innervate the mouse olfactory mucosa (OM). We further demonstrate that DA-DRD2 signaling in the nose plays important roles in regulating olfactory function using genetic and pharmacological approaches. Moreover, the local DA synthesis in mouse OM is reduced during hunger, which contributes to starvation-induced olfactory enhancement. Altogether, we demonstrate that nasal DA and DRD2 receptor can serve as the potential peripheral targets for olfactory modulation.

Adolescent administration of ketamine impairs excitatory synapse formation onto parvalbumin-positive GABAergic interneurons in mouse prefrontal cortex.

Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.

Controlling diurnal flower-opening time by manipulating the jasmonate pathway accelerates development of indica-japonica hybrid rice breeding.

Inter-subspecific indica-japonica hybrid rice (Oryza sativa) has the potential for increased yields over traditional indica intra-subspecies hybrid rice, but limited yield of F1 hybrid seed production (FHSP) hinders the development of indica-japonica hybrid rice breeding. Diurnal flower-opening time (DFOT) divergence between indica and japonica rice has been a major contributing factor to this issue, but few DFOT genes have been cloned. Here, we found that manipulating the expression of jasmonate (JA) pathway genes can effectively modulate DFOT to improve the yield of FHSP in rice. Treating japonica cultivar Zhonghua 11 (ZH11) with methyl jasmonate (MeJA) substantially advanced DFOT. Furthermore, overexpressing the JA biosynthesis gene OPDA REDUCTASE 7 (OsOPR7) and knocking out the JA inactivation gene CHILLING TOLERANCE 1 (OsHAN1) in ZH11 advanced DFOT by 1- and 2-h respectively; and knockout of the JA signal suppressor genes JASMONATE ZIM-DOMAIN PROTEIN 7 (OsJAZ7) and OsJAZ9 resulted in 50-min and 1.5-h earlier DFOT respectively. The yields of FHSP using japonica male-sterile lines GAZS with manipulated JA pathway genes were significantly higher than that of GAZS wildtype. Transcriptome analysis, cytological observations, measurements of elastic modulus and determination of cell wall components indicated that the JA pathway could affect the loosening of the lodicule cell walls by regulating their composition through controlling sugar metabolism, which in turn influences DFOT. This research has vital implications for breeding japonica rice cultivars with early DFOT to facilitate indica-japonica hybrid rice breeding.

An E3 ubiquitin ligase CSIT2 controls critical sterility-inducing temperature of thermo-sensitive genic male sterile rice.

Thermo-sensitive genic male sterile (TGMS) lines are the core of two-line hybrid rice (Oryza sativa). However, elevated or unstable critical sterility-inducing temperatures (CSITs) of TGMS lines are bottlenecks that restrict the development of two-line hybrid rice. However, the genes and molecular mechanisms controlling CSIT remain unknown. Here, we report the CRITICAL STERILITY-INDUCING TEMPERATURE 2 (CSIT2) that encodes a really interesting new gene (RING) type E3 ligase, controlling the CSIT of thermo-sensitive male sterility 5 (tms5)-based TGMS lines through ribosome-associated protein quality control (RQC). CSIT2 binds to the large and small ribosomal subunits and ubiquitinates 80S ribosomes for dissociation, and may also ubiquitinate misfolded proteins for degradation. Mutation of CSIT2 inhibits the possible damage to ubiquitin system and protein translation, which allows more proteins such as catalases to accumulate for anther development and inhibits abnormal accumulation of reactive oxygen species (ROS) and premature programmed cell death (PCD) in anthers, partly rescuing male sterility and raised the CSIT of tms5-based TGMS lines. These findings reveal a mechanism controlling CSIT and provide a strategy for solving the elevated or unstable CSITs of tms5-based TGMS lines in two-line hybrid rice.

Low-dose decitabine modulates myeloid-derived suppressor cell fitness via LKB1 in immune thrombocytopenia.

Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. Metabolic fitness of MDSCs is fundamental for its suppressive activity toward effector T cells. Our previous studies showed that the number and inhibitory function of MDSCs were impaired in patients with immune thrombocytopenia (ITP) compared with healthy controls. In this study, we analyzed the effects of decitabine on MDSCs from patients with ITP, both in vitro and in vivo. We found that low-dose decitabine promoted the generation of MDSCs and enhanced their aerobic metabolism and immunosuppressive functions. Lower expression of liver kinase 1 (LKB1) was found in MDSCs from patients with ITP, which was corrected by decitabine therapy. LKB1 short hairpin RNA (shRNA) transfection effectively blocked the function of MDSCs and almost offset the enhanced effect of decitabine on impaired MDSCs. Subsequently, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient (SCID) mice to induce ITP in murine models. Passive transfer of decitabine-modulated MDSCs significantly raised platelet counts compared with that of phosphate buffered saline-modulated MDSCs. However, when LKB1 shRNA-transfected MDSCs were transferred into SCID mice, the therapeutic effect of decitabine in alleviating thrombocytopenia was quenched. In conclusion, our study suggests that the impaired aerobic metabolism of MDSCs is involved in the pathogenesis of ITP, and the modulatory effect of decitabine on MDSC metabolism contributes to the improvement of its immunosuppressive function. This provides a possible mechanism for sustained remission elicited by low-dose decitabine in patients with ITP.

Fine and combinatorial regulation of key metabolic pathway for enhanced ß-alanine biosynthesis with non-inducible Escherichia coli.

ß-Alanine is the only ß-amino acid in nature and one of the most important three-carbon chemicals. This work was aimed to construct a non-inducible ß-alanine producer with enhanced metabolic flux towards ß-alanine biosynthesis in Escherichia coli. First of all, the assembled E. coli endogenous promoters and 5'-untranslated regions (PUTR) were screened to finely regulate the combinatorial expression of genes panDBS and aspBCG for an optimal flux match between two key pathways. Subsequently, additional copies of key genes (panDBS K104S and ppc) were chromosomally introduced into the host A1. On these bases, dynamical regulation of the gene thrA was performed to reduce the carbon flux directed in the competitive pathway. Finally, the ß-alanine titer reached 10.25 g/L by strain A14-R15, 361.7% higher than that of the original strain. Under fed-batch fermentation in a 5-L fermentor, a titer of 57.13 g/L ß-alanine was achieved at 80 h. This is the highest titer of ß-alanine production ever reported using non-inducible engineered E. coli. This metabolic modification strategy for optimal carbon flux distribution developed in this work could also be used for the production of various metabolic products.

NSD2 modulates Drp1-mediated mitochondrial fission in chronic renal allograft interstitial fibrosis by methylating STAT1.

Renal interstitial fibrosis/tubular atrophy (IF/TA) is a prominent pathological feature of chronic allograft dysfunction (CAD). Our previous study has demonstrated that epithelial-mesenchymal transition (EMT) plays a significant role in shaping the development of IF/TA. Nuclear SET domain (NSD2), a histone methyltransferase catalyzing methylation at lysine 36 of histone 3, is crucially involved in the development and progression of solid tumors. But its role in the development of renal allograft interstitial fibrosis has yet to be elucidated. Here, we characterize NSD2 as a crucial mediator in the mouse renal transplantation model in vivo and a model of tumor necrosis factor-α (TNF-α) stimulated-human renal tubular epithelial cells (HK-2) in vitro. Functionally, NSD2 knockdown inhibits EMT, dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in mice. Conversely, NSD2 overexpression exacerbates fibrosis-associated phenotypes and mitochondrial fission in tubular cells. Mechanistically, tubular NSD2 aggravated the Drp-1 mediated mitochondrial fission via STAT1/ERK/PI3K/Akt signaling pathway in TNF-α-induced epithelial cell models. Momentously, mass spectrometry (MS) Analysis and site-directed mutagenesis assays revealed that NSD2 interacted with and induced Mono-methylation of STAT1 on K173, leading to its phosphorylation, IMB1-dependent nuclear translocation and subsequent influence on TNF-α-induced EMT and mitochondrial fission in NSD2-dependent manner. Collectively, these findings shed light on the mechanisms and suggest that targeting NSD2 could be a promising therapeutic approach to enhance tubular cell survival and alleviate interstitial fibrosis in renal allografts during CAD.

Gestational Exposure to PM2.5 and Specific Constituents, Meconium Metabolites, and Neonatal Neurobehavioral Development: A Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been inversely associated with neonatal neurological development. However, the associations of exposure to specific PM2.5 constituents with neonatal neurological development remain unclear. We investigated these associations and examined the mediating role of meconium metabolites in a Chinese birth cohort consisting of 294 mother-infant pairs. Our results revealed that exposure to PM2.5 and its specific constituents (i.e., organic matter, black carbon, sulfate, nitrate, and ammonium) in the second trimester, but not in the first or third trimester, was inversely associated with the total neonatal behavioral neurological assessment (NBNA) scores. The PM2.5 constituent mixture in the second trimester was also inversely associated with NBNA scores, and sulfate was identified as the largest contributor. Furthermore, meconium metabolome analysis identified four metabolites, namely, threonine, lysine, leucine, and saccharopine, that were associated with both PM2.5 constituents and NBNA scores. Threonine was identified as an important mediator, accounting for a considerable proportion (14.53-15.33%) of the observed inverse associations. Our findings suggest that maternal exposure to PM2.5 and specific constituents may adversely affect neonatal behavioral development, in which meconium metabolites may play a mediating role.

A comparison of behavioral paradigms assessing spatial memory in tree shrews.

Impairments in spatial navigation in humans can be preclinical signs of Alzheimer's disease. Therefore, cognitive tests that monitor deficits in spatial memory play a crucial role in evaluating animal models with early stage Alzheimer's disease. While Chinese tree shrews (Tupaia belangeri) possess many features suitable for Alzheimer's disease modeling, behavioral tests for assessing spatial cognition in this species are lacking. Here, we established reward-based paradigms using the radial-arm maze and cheeseboard maze for tree shrews, and tested spatial memory in a group of 12 adult males in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and task performance improved gradually until reaching a plateau in all 3 mazes. However, spatial learning was compromised post-lesion in the 2 newly developed tasks, whereas memory retrieval was impaired in the water maze task. These results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring progressive cognitive decline in aged or genetically modified tree shrews that develop Alzheimer's disease-like symptoms. This study may facilitate the utilization of tree shrew models in Alzheimer's disease research.

A retrospective study of mineral and bone disorder in kidney transplant recipients: Single-center experience.

BACKGROUND: The status of mineral and bone disorder (MBD) after kidney transplantation is not fully understood, and the assessment of abnormal mineral and bone metabolism in kidney transplant recipients (KTRs) has not been standardized. MATERIALS AND METHODS: We performed a retrospective analysis of 292 KTRs in our center. The levels of biochemical markers of bone metabolism and bone mineral density (BMD) were assessed. We evaluated the influencing factors of BMD using linear regression analysis. And correlation test was used for the correlation analysis between bone metabolism indicators and other indicators. RESULTS: Postoperative MBD mainly manifested as hypercalcemia (8.9%), hypophosphatemia (27.1%), low levels of 25-hydroxyvitamin D(25(OH)vitD) (67.0%), hyperparathyroidism (50.6%), and high levels of bone turnover markers (BTMs). The prevalence of osteopenia/osteoporosis in the femoral neck (FN) and lumbar spine (LS) was 20.1%/2.8% and 26.1%/3.6%, respectively. Multivariate analysis indicated that FN BMD was positively associated with body mass index (BMI) and negatively associated with acute rejection history (p < 0.05); while LS BMD was positively associated with BMI, and negatively associated with intact parathyroid hormone (iPTH) (p < 0.05). Biochemical markers of bone metabolism were affected by age, sex, preoperative dialysis mode and time, postoperative time, transplanted kidney function, and iPTH levels. LS BMD was negatively correlated with iPTH and BTMs (p < 0.05). CONCLUSION: MBD persisted after kidney transplantation. Decreased bone mass was associated with persistent hyperparathyroidism, acute rejection history, low BMI, advanced age, and menopause. Dynamic monitoring of bone metabolism index and BMD helps to assess MBD after kidney transplantation.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

The association between high-oxygen saturation and prognosis for intracerebral hemorrhage.

BACKGROUND: Concerns about the adverse effects of excessive oxygen have grown over the years. This study investigated the relationship between high oxygen saturation and short-term prognosis of patients with spontaneous intracerebral hemorrhage (sICH) after liberal use of oxygen. METHODS: This retrospective cohort study collected data from the Medical Information Mart for Intensive Care III (MIMIC-III) database (ICU cohort) and a tertiary stroke center (general ward cohort). The data on pulse oximetry-derived oxygen saturation (SpO2) during the first 24 h in ICU and general wards were respectively extracted. RESULTS: Overall, 1117 and 372 patients were included in the ICU and general ward cohort, respectively. Among the patients from the ICU cohort, a spoon-shaped association was observed between minimum SpO2 and the risk of in-hospital mortality (non-linear P<0.0001). In comparison with minimum SpO2 of 93-97%, the minimum SpO2>97% was associated with a significantly higher risk of in-hospital mortality after adjustment for confounders. Sensitivity analysis conducted using propensity score matching did not change this significance. The same spoon-shaped association between minimum SpO2 and the risk of in-hospital mortality was also detected for the general ward cohort. In comparison with the group with 95-97% SpO2, the group with SpO2>97% showed a stronger association with, but non-significant risk for, in-hospital mortality after adjustment for confounders. The time-weighted average SpO2>97% was associated significantly with in-hospital mortality in both cohorts. CONCLUSION: Higher SpO2 (especially a minimum SpO2>97%) was unrewarding after liberal use of oxygen among patients with sICH and might even be potentially detrimental.

Risk factors on surgical compliance and its impact on survival outcomes in meningioma patients: a SEER-based retrospective propensity-score matched analysis.

BACKGROUND: This study aimed to analyze the effect of surgical compliance on the survival outcome of patients with meningioma and explore the factors affecting surgical compliance. METHODS: We selected data from the Surveillance, Epidemiology, and End Results database for 122,632 meningioma patients diagnosed between 2004 and 2018. The effect of surgical compliance on patients' overall survival (OS) was analyzed through Cox regression and Kaplan-Meier curves. Independent risk factors for surgical compliance were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves. Furthermore, we used univariate and multivariate logistic regression analyses to evaluate relevant variables linked to adherence with meningioma surgery. Moreover, 1:1 propensity score matching was applied to assess the validity of the results in patients with favorable and poor surgical compliance. RESULTS: A total of 48,735 were eligible from the initial cohort of 122,632 patients with meningioma. Among them, 45,038 (92.40%) exhibited good surgical compliance, while 3697 (7.60%) had poor surgical compliance. The rate of patients with good surgical compliance was significantly higher than that of patients with inadequate surgical compliance (p < 0.001). Moreover, surgical compliance is an independent prognostic factor for OS in meningioma patients. Univariate Cox regression analysis indicated that individuals with poor surgical compliance demonstrated lower OS rates than those with good surgical compliance (hazard ratio [HR 2.404; 95% confidence interval [CI] 2.276-2.54, p < 0.001], consistent with the observation in the multivariate analysis (HR 1.564; 95% CI 1.471-1.663, p < 0.001). We developed a prediction model using seven variables: age, sex, race, tumor behavior recode, tumor size, family income, and residential setting (p < 0.05). Surgical compliance was associated with patient age, sex, race, tumor behavior recode, tumor size, family income, and residential setting by logistic regression analysis. CONCLUSIONS: Surgical compliance emerged as an independent prognostic factor for survival in patients with meningioma. Poor surgical compliance was associated with older age, black and other races, females, advanced-stage tumors, larger tumor size, lower household income, and rural residence. When patients experienced these conditions, OS was shorter, requiring more aggressive treatment.

A Novel Method for Precision Measurement and Result Optimization of Detuning Angle for KDP Crystals.

In this paper, we investigate the theory of energy distribution when divergent light undergoes harmonic conversion in KDP crystals, and based on this theory, we design and construct a precision measuring instrument for the detuning angle of (KDP) Crystals (MIDC). The device can obtain the detuning angle of the crystal by a single measurement with an average measurement error of 72.78 urad. At the same time, it also has the function of scanning the full aperture of the crystals. Using the MIDC, it is possible to quickly measure the KDP crystal at a single point and quickly scan the crystal detuning angle at full aperture. In addition, we conduct a theoretical study on the variation of detuning angle caused by gravity-influencing factors under online conditions, propose an optimization formula for the offline measurement results of detuning angle, and calculate the optimized values of detuning angle for two kinds of crystals under 45° online conditions. We finally study the error source of the MIDC device, analyze the trend of the influence of positioning errors of the crystal and optical elements on the detuning angle measurement results, and provide theoretical support for the error monitoring and correction of MIDC.