Tertiary lymphoid structural heterogeneity determines tumour immunity and prospects for clinical application.

Tertiary lymphoid structures (TLS) are clusters of immune cells that resemble and function similarly to secondary lymphoid organs (SLOs). While TLS is generally associated with an anti-tumour immune response in most cancer types, it has also been observed to act as a pro-tumour immune response. The heterogeneity of TLS function is largely determined by the composition of tumour-infiltrating lymphocytes (TILs) and the balance of cell subsets within the tumour-associated TLS (TA-TLS). TA-TLS of varying maturity, density, and location may have opposing effects on tumour immunity. Higher maturity and/or higher density TLS are often associated with favorable clinical outcomes and immunotherapeutic response, mainly due to crosstalk between different proportions of immune cell subpopulations in TA-TLS. Therefore, TLS can be used as a marker to predict the efficacy of immunotherapy in immune checkpoint blockade (ICB). Developing efficient imaging and induction methods to study TA-TLS is crucial for enhancing anti-tumour immunity. The integration of imaging techniques with biological materials, including nanoprobes and hydrogels, alongside artificial intelligence (AI), enables non-invasive in vivo visualization of TLS. In this review, we explore the dynamic interactions among T and B cell subpopulations of varying phenotypes that contribute to the structural and functional diversity of TLS, examining both existing and emerging techniques for TLS imaging and induction, focusing on cancer immunotherapies and biomaterials. We also highlight novel therapeutic approaches of TLS that are being explored with the aim of increasing ICB treatment efficacy and predicting prognosis.

Screening of Spinal Muscular Atrophy Carriers and Prenatal Diagnosis in Pregnant Women in Yancheng, China.

Spinal muscular atrophy (SMA) is a neuromuscular disorder with an autosomal recessive inheritance pattern. Patients with severe symptoms may suffer respiratory failure, leading to death. The homozygous deletion of exon 7 in the SMN1 gene accounts for nearly 95% of all cases. Population carrier screening for SMA and prenatal diagnosis by amniocentesis for high-risk couples can assist in identifying the risk of fetal disease. We provided the SMA carrier screening process to 55,447 pregnant women in Yancheng from October 2020 to December 2022. Among them, 8185 participated in this process, with a participation rate of around 14.76% (95% CI 14.47-15.06%). Quantitative real-time polymerase chain reaction (qPCR) was used to detect deletions of SMN1 exons 7 and 8 (E7, E8) in screened pregnant women. 127 were identified as carriers (111 cases of E7 and E8 heterozygous deletions, 15 cases of E7 heterozygous deletions, and 1 case of E7 heterozygous deletions and E8 homozygous deletions), resulting in a carrying rate of around 1.55% (95% CI 1.30-1.84%). After genetic counseling, 114 spouses of pregnant women who tested positive underwent SMA carrier screening; three of them were screened as SMA carriers. Multiplexed ligation-dependent probe amplification (MLPA) was used for the prenatal diagnosis of the fetuses of high-risk couples. Two of them exhibited two copies of SMN1 exon 7 (normal), and the pregnancy was continued; one exhibited no copies of SMN1 exon 7 and exon 8 (SMA patient), and the pregnancy was terminated. Analyzing SMN1 mutations in Yancheng and provide clinical evidence for SMA genetic counseling and birth defect prevention. Interventional prenatal diagnosis for high-risk families can promote informed reproductive selection and prepare for the fetus's early treatment.

[The value of chromosomal microarray analysis and fluorescence in situ hybridization for the prenatal diagnosis of chromosomal mosaicisms].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms. METHODS: A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases. RESULTS: Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms). CONCLUSION: For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.

Effects of Cigarette Smoke Exposure on the Gut Microbiota and Liver Transcriptome in Mice Reveal Gut-Liver Interactions.

Cigarette smoke exposure has a harmful impact on health and increases the risk of disease. However, studies on cigarette-smoke-induced adverse effects from the perspective of the gut-liver axis are lacking. In this study, we evaluated the adverse effects of cigarette smoke exposure on mice through physiological, biochemical, and histopathological analyses and explored cigarette-smoke-induced gut microbiota imbalance and changes in liver gene expression through a multiomics analysis. We demonstrated that cigarette smoke exposure caused abnormal physiological indices (including reduced body weight, blood lipids, and food intake) in mice, which also triggered liver injury and induced disorders of the gut microbiota and liver transcriptome (especially lipid metabolism). A significant correlation between intestinal bacterial abundance and the expression of lipid-metabolism-related genes was detected, suggesting the coordinated regulation of lipid metabolism by gut microbiota and liver metabolism. Specifically, Salmonella (harmful bacterium) was negatively and positively correlated with up- (such as Acsl3 and Me1) and downregulated genes (such as Angptl4, Cyp4a12a, and Plin5) involved in lipid metabolism, while Ligilactobacillus (beneficial bacterium) showed opposite trends with these genes. Our results clarified the key role of gut microbiota in liver damage and metabolism and improved the understanding of gut-liver interactions caused by cigarette smoke exposure.

Exploring the Mystery of the Tetrahydrobiopterin Synthetic Defect Lethal Mutant leml from Birth to Death in the Silkworm Bombyx mori.

Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals, and BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. In the silkworm natural homozygous mutant leml, the key enzyme sepiapterin reductase (BmSPR) in the de novo synthesis pathway of BH4 is inactivated, resulting in severe deficiency of BH4 synthesis. However, it is not known why the leml larvae can survive to the second-instar stage and which pathways lead to their death when BH4 is deficient. Here, we quantified BH4 and found that the fertilized eggs contained large amounts of BH4 transferred from the mother to the offspring, maintaining its normal development in the embryo and the first instar. Subsequently, we investigated the multiple pathways in which BH4 is involved as a cofactor. The results showed that BH4 deficiency in silkworms blocked the melanin synthesis pathway, caused an insufficient degree of epidermal sclerosis, disordered tyrosine metabolism, and damaged mitochondria. On the other hand, BH4 deficiency led to the uncoupling of nitric oxide synthase (BmNOS), a reduced NO production, and a significantly reduced fat in fat body catalyzation by phospholipase A2, resulting in an impaired immune system. Meanwhile, the uncoupling of BmNOS increased the O2- content, damaged the DNA, and caused the apoptosis of the body cells. Taken together, BH4 is critical for the life and death of leml mutants. This study lays a foundation for the further exploration of lepidopteran insects and provides an important basis for the treatment of human BH4 deficiency-related diseases.

Functional characterization and regulatory mechanism of wheat CPK34 kinase in response to drought stress.

BACKGROUND: Drought is one of the most adverse environmental factors limiting crop productions and it is important to identify key genetic determinants for food safety. Calcium-dependent protein kinases (CPKs) are known to be involved in plant growth, development, and environmental stresses. However, biological functions and regulatory mechanisms of many plant CPKs have not been explored. In our previous study, abundance of the wheat CPK34 (TaCPK34) protein was remarkably upregulated in wheat plants suffering from drought stress, inferring that it could be involved in this stress. Therefore, here we further detected its function and mechanism in response to drought stress. RESULTS: Transcripts of the TaCPK34 gene were significantly induced after PEG-stimulated water deficiency (20% PEG6000) or 100 µM abscisic acid (ABA) treatments. The TaCPK34 gene was transiently silenced in wheat genome by using barley stripe mosaic virus-induced silencing (BSMV-VIGS) method. After 14 days of drought stress, the transiently TaCPK34-silenced wheat seedlings showed more sensitivity compared with control, and the plant biomasses and relative water contents significantly decreased, whereas soluble sugar and MDA contents increased. The iTRAQ-based quantitative proteomics was employed to measure the protein expression profiles in leaves of the transiently TaCPK34-silenced wheat plants after drought stress. There were 6103 proteins identified, of these, 51 proteins exhibited significantly altered abundance, they were involved in diverse function. And sequence analysis on the promoters of genes, which encoded the above identified proteins, indicated that some promoters harbored some ABA-responsive elements. We determined the interactions between TaCPK34 and three identified proteins by using bimolecular fluorescent complementation (BiFC) method and our data indicated that TaCPK34directly interacted with the glutathione S-transferase 1 and prx113, respectively. CONCLUSIONS: Our study suggested that the TaCPK34 gene played positive roles in wheat response to drought stress through directly or indirectly regulating the expression of ABA-dependent manner genes, which were encoding identified proteins from iTRAQ-based quantitative proteomics. And it could be used as one potential gene to develop crop cultivars with improved drought tolerance.

Effect of hot water treatment on chilling injury and lignification of cold-stored fresh areca nut (Areca catechu L.).

Fresh areca nut is widely favored by consumers in South and Southeast Asia. However, postharvest areca nut perished quickly and was vulnerable to chilling injury (CI) and lignification during traditional cold storage. In order to alleviate this situation, hot water treatment was applied to investigate its effect on CI and lignification of fresh areca nut during cold storage at 13 °C. Areca nuts were submersed in hot water at 45 °C (HW45) and 50 °C (HW50) for short-term 5 min compared to fruit submersed in water at 20 °C (CT), then stored at 13 °C with 90% humidity for 60 days. CI, malondialdehyde (MDA), electrolyte leakage (EL), lignin and total phenolic content, related enzymes including phenylalanine ammonia-lyase (PAL), cinnamyl alcohol dehydrogenase (CAD) and peroxidase activity (POD) were examined. Results indicated that two HW treatments both induced chilling tolerance and delayed lignification of areca nut to varying degrees during cold storage compared with the CT. Among which, HW45 treated-areca nuts had the lowest CI, MDA content and EL while maintaining the highest total phenolic content. Moreover, no significant effects were found between HW45 and HW50 on tissue lignification, but they both effectively blocked lignin accumulation by inhibiting PAL, CAD and POD activities compared with the CT. The present study provided a safe physical method to mitigate CI and delay tissue lignification in cold-stored areca nut.

Large-scale Proteomics Combined with Transgenic Experiments Demonstrates An Important Role of Jasmonic Acid in Potassium Deficiency Response in Wheat and Rice.

Potassium (K+) is the most abundant inorganic cation in plants, and molecular dissection of K+ deficiency has received considerable interest in order to minimize K+ fertilizer input and develop high quality K+-efficient crops. However, the molecular mechanism of plant responses to K+ deficiency is still poorly understood. In this study, 2-week-old bread wheat seedlings grown hydroponically in Hoagland solution were transferred to K+-free conditions for 8 d, and their root and leaf proteome profiles were assessed using the iTRAQ proteome method. Over 4000 unique proteins were identified, and 818 K+-responsive protein species showed significant differences in abundance. The differentially expressed protein species were associated with diverse functions and exhibited organ-specific differences. Most of the differentially expressed protein species related to hormone synthesis were involved in jasmonic acid (JA) synthesis and the upregulated abundance of JA synthesis-related enzymes could result in the increased JA concentrations. Abundance of allene oxide synthase (AOS), one key JA synthesis-related enzyme, was significantly increased in K+-deficient wheat seedlings, and its overexpression markedly increased concentrations of K+ and JA, altered the transcription levels of some genes encoding K+-responsive protein species, as well as enhanced the tolerance of rice plants to low K+ or K+ deficiency. Moreover, rice AOS mutant (osaos) exhibited more sensitivity to low K+ or K+ deficiency. Our findings could highlight the importance of JA in K+ deficiency, and imply a network of molecular processes underlying plant responses to K+ deficiency.

Late recanalisation beyond 24 hours is associated with worse outcome: an observational study.

OBJECTIVES: We evaluated the rate of late recanalisation beyond 24 h after intravenous thrombolysis (IVT) and its relationship with haemorrhagic transformation and outcome. METHODS: We reviewed prospectively collected clinical and imaging data from acute ischaemic stroke patients with distal internal carotid artery or proximal middle cerebral artery occlusion who underwent angiography on admission, 24 h and 1 week after IVT. Patients were trichotomised according to vascular status: timely recanalisation (<24 h), late recanalisation (24 h-7 days), and no recanalisation. RESULTS: Non-invasive angiography revealed timely recanalisation in 52 (50.0 %) patients, late recanalisation in 25 (24.0 %) patients, and no recanalisation in 27 (26.0 %) patients. Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation (odds ratio 6.674; 95 % CI: 1.197 to 37.209; p = 0.030). In patients without timely recanalisation, shift analysis indicated that late recanalisation led to a worse modified Rankin Scale score (odds ratio 6.787; 95 % CI: 2.094 to 21.978; p = 0.001). CONCLUSIONS: About half of all patients without recanalisation by 24 h after IVT may develop late recanalisation within 1 week, along with higher mRS scores by 3 months. Pre-existing atrial fibrillation is an independent predictor for late recanalisation. KEY POINTS: • About half of patients may develop late recanalisation within 1 week. • Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation. • Late recanalisation led to a higher mRS score than no recanalisation.

Functional Analysis of a Wheat AGPase Plastidial Small Subunit with a Truncated Transit Peptide.

ADP-glucose pyrophosphorylase (AGPase), the key enzyme in starch synthesis, consists of two small subunits and two large subunits with cytosolic and plastidial isoforms. In our previous study, a cDNA sequence encoding the plastidial small subunit (TaAGPS1b) of AGPase in grains of bread wheat (Triticum aestivum L.) was isolated and the protein subunit encoded by this gene was characterized as a truncated transit peptide (about 50% shorter than those of other plant AGPS1bs). In the present study, TaAGPS1b was fused with green fluorescent protein (GFP) in rice protoplast cells, and confocal fluorescence microscopy observations revealed that like other AGPS1b containing the normal transit peptide, TaAGPS1b-GFP was localized in chloroplasts. TaAGPS1b was further overexpressed in a Chinese bread wheat cultivar, and the transgenic wheat lines exhibited a significant increase in endosperm AGPase activities, starch contents, and grain weights. These suggested that TaAGPS1b subunit was targeted into plastids by its truncated transit peptide and it could play an important role in starch synthesis in bread wheat grains.

Thrombus Length Estimation on Delayed Gadolinium-Enhanced T1.

BACKGROUND AND PURPOSE: Previous studies revealed a close relationship between thrombus length and recanalization rate after intravenous thrombolysis (IVT). As a novel approach, we prospectively adjusted the order of sequence acquisition to obtain delayed gadolinium-enhanced T1 (dGE-T1) and thereby assess thrombus length on dGE-T1 to evaluate its predictive value for recanalization after IVT. METHODS: We reviewed prospectively collected clinical and imaging data from acute ischemic stroke patients with middle cerebral artery occlusion who underwent multimodal magnetic resonance imaging before and 24 hours after IVT. Perfusion-weighted imaging was performed followed by conventional T1. We measured thrombus length on dGE-T1 and examined its association with middle cerebral artery recanalization. RESULTS: Of the included 74 patients, the median age was 66 years and 28 (37.8%) were women. Thrombus length was 8.18±4.56 mm on dGE-T1, which was an acceptable predictor for no recanalization (odds ratio, 1.196; 95% confidence interval, 1.015-1.409; P=0.033), with a receiver-operator characteristic of 0.732 (95% confidence interval, 0.619-0.845; P=0.001). The optimal cut-off point was identified at 6.77 mm, which yielded a sensitivity of 77.8%, a specificity of 57.9%, and an odds ratio of 4.81 (95% confidence interval, 1.742-13.292; P=0.002). Moreover, no one achieved recanalization after IVT when length of thrombus exceeded 14 mm on dGE-T1. CONCLUSIONS: The dGE-T1, obtained by simply adjusting scanning order in multimodal magnetic resonance imaging protocol, is a useful tool for thrombus length estimation and middle cerebral artery recanalization prediction after IVT.

Timing of Occurrence Is the Most Important Characteristic of Spot Sign.

BACKGROUND AND PURPOSE: Most previous studies have used single-phase computed tomographic angiography to detect the spot sign, a marker for hematoma expansion (HE) in spontaneous intracerebral hemorrhage. We investigated whether defining the spot sign based on timing on perfusion computed tomography (CTP) would improve its specificity for predicting HE. METHODS: We prospectively enrolled supratentorial spontaneous intracerebral hemorrhage patients who underwent CTP within 6 hours of onset. Logistic regression was performed to assess the risk factors for HE and poor outcome. Predictive performance of individual CTP spot sign characteristics were examined with receiver operating characteristic analysis. RESULTS: Sixty-two men and 21 women with spontaneous intracerebral hemorrhage were included in this analysis. Spot sign was detected in 46% (38/83) of patients. Receiver operating characteristic analysis indicated that the timing of spot sign occurrence on CTP had the greatest area under receiver operating characteristic curve for HE (0.794; 95% confidence interval, 0.630-0.958; P=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the presence of early-occurring spot sign (ie, spot sign before 23.13 seconds) was an independent predictor not only of HE (odds ratio=28.835; 95% confidence interval, 6.960-119.458; P<0.001), but also of mortality at 3 months (odds ratio =22.377; 95% confidence interval, 1.773-282.334; P=0.016). Moreover, the predictive performance showed that the redefined early-occurring spot sign maintained a higher specificity for HE compared with spot sign (91% versus 74%). CONCLUSIONS: Redefining the spot sign based on timing of contrast leakage on CTP to determine early-occurring spot sign improves the specificity for predicting HE and 3-month mortality. The use of early-occurring spot sign could improve the selection of ICH patients for potential hemostatic therapy.

Virus-Induced Gene Silencing Identifies an Important Role of the TaRSR1 Transcription Factor in Starch Synthesis in Bread Wheat.

The function of a wheat starch regulator 1 (TaRSR1) in regulating the synthesis of grain storage starch was determined using the barley stripe mosaic virus-virus induced gene-silencing (BSMV-VIGS) method in field experiments. Chlorotic stripes appeared on the wheat spikes infected with barley stripe mosaic virus-virus induced gene-silencing- wheat starch regulator 1 (BSMV-VIGS-TaRSR1) at 15 days after anthesis, at which time the transcription levels of the TaRSR1 gene significantly decreased. Quantitative real-time PCR was also used to measure the transcription levels of 26 starch synthesis-related enzyme genes in the grains of BSMV-VIGS-TaRSR1-silenced wheat plants at 20, 27, and 31 days after anthesis. The results showed that the transcription levels of some starch synthesis-related enzyme genes were markedly induced at different sampling time points: TaSSI, TaSSIV, TaBEIII, TaISA1, TaISA3, TaPHOL, and TaDPE1 genes were induced at each of the three sampling time points and TaAGPS1-b, TaAGPL1, TaAGPL2, TaSSIIb, TaSSIIc, TaSSIIIb, TaBEI, TaBEIIa, TaBEIIb, TaISA2, TaPHOH, and TaDPE2 genes were induced at one sampling time point. Moreover, both the grain starch contents, one thousand kernel weights, grain length and width of BSMV-VIGS-TaRSR1-infected wheat plants significantly increased. These results suggest that TaRSR1 acts as a negative regulator and plays an important role in starch synthesis in wheat grains by temporally regulating the expression of specific starch synthesis-related enzyme genes.

[Signifiance of brush sign on susceptibility-weighted imaging predicts hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke].

OBJECTIVE: To assess brush sign (BS) on susceptibility-weighted imaging (SWI) in prediction of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis(IVT). METHODS: Patients with acute cerebral ischemic stroke, who had major cerebral artery occlusion (internal carotid artery, middle cerebral artery M1 and M2), treated with intravenous recombinant tissue plasminogen activator (rt-PA) from August 2009 to October 2014 in the Second Affiliated Hospital, Zhejiang University School of Medicine, were enrolled in the study. All patients underwent SWI scanning. The asymmetry index (AI) was defined as the difference of intensity between ischemic and normal hemispheres on the SWI phase map; according to AI values patients were divided into 3 groups: BS=0(n=9), BS=1 (n=39) and BS=2 (n=18). The relationships between BS and HT and the clinical outcome among the 3 groups were analyzed. RESULTS: Sixty-six patients aged 68 ± 13 years were included in the study, including 44 males (67%) and 22 females (33%), and 44 (67%) with acute ischemic stroke. The mean pre-treatment National Institutes of Health Stroke Scale (NIHSS) score was 13 (6-17), and the onset to needle time was (252 ± 88) min. Twenty-six (39.4%) patients had HT, including 18 cases (27.3%) with HI and 8 cases (12.1%) with PH; BS was observed more frequently in HT group than non-HT group. Binary logistic regression analysis showed that BS was independently associated with HT of patients with acute ischemic stroke following IVT (OR=2.589, 95% CI: 1.080-6.210, P=0.033). In those without reperfusion after IVT, patients with higher BS grade had higher HT rate (P=0.023). CONCLUSION: Brush sign on SWI can be used for predicting hemorrhagic transformation after intravenous thrombolysis in patients with acute ischemic stroke.

[Older age is not related to hemorrhagic transformation and favorable outcomes in patients with wake-up ischemic stroke undergoing intravenous thrombolytic therapy].

OBJECTIVE: To investigate factors related to hemorrhagic transformation and favorable outcomes in wake-up ischemic stroke (WUIS) patients undergoing intravenous thrombolytic therapy. METHODS: Clinical data of 600 patients undergoing multimodal image-guided intravenous recombinant tissue plasminogen activator (rt-PA) therapy in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine center from May 2009 to May 2015 were retrospectively analyzed. Among 600 patients, 68 were diagnosed as WUIS including 17 cases aged 80 or older. Hemorrhagic transformation within the first 24 h after thrombolysis was assessed according to ECASS II criteria. Favorable outcome was defined as three-month modified Rankin Scale (mRS) 0-3. Univariate and binary logistic regression were used to analyze the risk factors of hemorrhagic transformation and poor clinical outcomes in WUIS patients. RESULTS: Univariate analysis showed that WUIS patients aged ≥ 80 years had a lower rate in males (41.2% vs 76.5%, P=0.007), smokers (11.8% vs 43.1%, P=0.019) and favorable outcome (52.9% vs 78.4%, P=0.043); and a higher rate of cardiac embolism (64.7% vs 35.3%, P=0.034) compared with those aged <80 years. Binary logistic regression showed that age was not an independent risk factor for favorable outcome (OR=0.524, 95% CI:0.141-1.953, P=0.336) or hemorrhagic transformation (OR=1.039, 95% CI: 0.972-1.111, P=0.262). CONCLUSION: Older age is not related to the favorable outcome or hemorrhagic transformation in WUIS patients undergoing multimodal image-guided intravenous thrombolytic therapy.

Comparison of ciprofol-alfentanil and propofol-alfentanil sedation during bidirectional endoscopy: A prospective, double-blind, randomised, controlled trial.

BACKGROUND: Although propofol is widely used for gastrointestinal endoscopic sedation, cardiopulmonary adverse events remain common. Ciprofol is a new intravenous anaesthetic agent demonstrating respiratory and hemodynamic stability. AIMS: This study aimed to clarify the benefits of ciprofol combined with alfentanil in bidirectional endoscopy (esophagogastroduodenoscopy followed by colonoscopy) to reduce adverse events and improve post-endoscopic recovery. METHODS: A total of 185 patients scheduled to undergo bidirectional endoscopy were randomly divided into two groups: ciprofol combined with alfentanil or propofol combined with alfentanil. All patients received 7 µg/kg alfentanil intravenously before the study drugs were administered. The propofol group received a bolus of 1.2 mg/kg (0.12 ml/kg) propofol intravenously, whereas the ciprofol group received a bolus of 0.3 mg/kg (0.12 ml/kg) ciprofol intravenously. The primary outcome was the proportion of patients with cardiopulmonary adverse events (i.e., any one of the airway obstruction, apnoea, hypotension, hypertension, bradycardia, tachycardia or arrhythmias). RESULTS: Compared with propofol, ciprofol reduced cardiopulmonary adverse events by 43.51 % (34.4% vs. 60.9 %, P <0.001), mitigated respiratory adverse events by 54.74 % (17.2% vs. 38.0 %, P = 0.002) overall and by 59.05 % (12.9% vs. 31.5 %, P = 0.002) during the induction period. CONCLUSIONS: Ciprofol can significantly decrease respiratory depression events and provides a better sedative efficacy than propofol with higher recovery quality and satisfaction.

Engineering natural microbiomes toward enhanced bioremediation by microbiome modeling.

Engineering natural microbiomes for biotechnological applications remains challenging, as metabolic interactions within microbiomes are largely unknown, and practical principles and tools for microbiome engineering are still lacking. Here, we present a combinatory top-down and bottom-up framework to engineer natural microbiomes for the construction of function-enhanced synthetic microbiomes. We show that application of herbicide and herbicide-degrader inoculation drives a convergent succession of different natural microbiomes toward functional microbiomes (e.g., enhanced bioremediation of herbicide-contaminated soils). We develop a metabolic modeling pipeline, SuperCC, that can be used to document metabolic interactions within microbiomes and to simulate the performances of different microbiomes. Using SuperCC, we construct bioremediation-enhanced synthetic microbiomes based on 18 keystone species identified from natural microbiomes. Our results highlight the importance of metabolic interactions in shaping microbiome functions and provide practical guidance for engineering natural microbiomes.

Deep-Learning-Based Nanomechanical Vibration for Rapid and Label-Free Assay of Epithelial Mesenchymal Transition.

Cancer is a profound danger to our life and health. The classification and related studies of epithelial and mesenchymal phenotypes of cancer cells are key scientific questions in cancer research. Here, we investigated cancer cell colonies from a mechanical perspective and developed an assay for classifying epithelial/mesenchymal cancer cell colonies using the biomechanical fingerprint in the form of "nanovibration" in combination with deep learning. The classification method requires only 1 s of vibration data and has a classification accuracy of nearly 92.5%. The method has also been validated for the screening of anticancer drugs. Compared with traditional methods, the method has the advantages of being nondestructive, label-free, and highly sensitive. Furthermore, we proposed a perspective that subcellular structure influences the amplitude and spectrum of nanovibrations and demonstrated it using experiments and numerical simulation. These findings allow internal changes in the cell colony to be manifested by nanovibrations. This work provides a perspective and an ancillary method for cancer cell phenotype diagnosis and promotes the study of biomechanical mechanisms of cancer progression.

Treatment of dissecting cellulitis of the scalp with erbium: YAG laser: a case series.

Dissecting cellulitis of the scalp (DCS) is a rare recurrent inflammatory disease of unknown etiology. Ideal treatment of DCS remains unclear. We treated DCS with 2940-nm erbium Yttrium-aluminum-garnet (YAG) laser in 12 patients and assessed the efficacy by Physicians Global Assessment (PGA), number of inflammatory nodules, abscesses, and area of alopecia. After a mean treating session of 2.2 months, 10 patients reached PGA 0 (initial PGA 1) or 1 (initial PGA ≥2). At the end of treatment, there was 84%, 100%, and 74% regression in nodules, abscesses, and alopecia area, respectively. No severe adverse effect was observed. 2940-nm erbium: YAG laser may be an effective and safe way to treat DCS resistant to other therapies.

Identification of a Novel Mutation of Extracellular Matrix Protein 1 Gene in a Chinese Family with Lipoid Proteinosis.

Lipoid proteinosis (LP) is a rare autosomal recessive disorder caused by mutations in extracellular matrix protein 1 (ECM1), a glycoprotein expressed in skin. Whole-exome sequencing (WES) was used to investigate two Chinese siblings with suggestive clinical features of LP. They shared one known (c.960G>A) and one novel (c.1081G>T) pathogenic variant in ECM1 gene, inherited from their unaffected parents. The novel mutation (c.1081G>T) led to a termination codon at position 361 and caused nonsense-mediated mRNA decay and lost the function. Our finding expands the genetic etiology spectrum of LP.