Bacterial surface display of PETase mutants and MHETase for an efficient dual-enzyme cascade catalysis.

Biological degradation of PET plastic holds great potential for plastic recycling. However, the high costs associated with preparing free enzymes for degrading PET make it unfeasible for industrial applications. Hence, we developed various cell catalysts by surface-displaying PETase mutants and MHETase using autotransporters in E. coli and P. putida. The efficiency of surface display was enhanced through modifying the host, co-expressing molecular chaperones, and evoluting the autotransporter. In strain EC9F, PET degradation rate was boosted to 3.85 mM/d, 51-fold and 23-fold increase compared to free enzyme and initial strain ED1, respectively. The reusability of cell catalyst EC9F was demonstrated with over 38 % and 30 % of its initial activity retained after 22 cycles of BHET degradation and 3 cycles of PET degradation. The highest reported PET degradation rate of 4.95 mM/d was achieved by the dual-enzyme cascade catalytic system EC9F+EM2+R, a mixture of cell catalyst EC9F and EM2 with surfactant rhamnolipid.

Relationship between Neutrophil-to-Lymphocyte Ratio and Liver Fibrosis in Nonalcoholic Fatty Liver Disease Among Adults in the United States: Data from the National Health and Nutrition Examination Survey 2017-2018.

BACKGROUND/AIMS:  The relationship between neutrophil-to-lymphocyte ratio (NLR) and liver fibrosis in nonalcoholic fatty liver disease remains controversial. The aim of this study was to examine the association between NLR and liver fibrosis. MATERIALS AND METHODS:  We conducted a cross-sectional analysis using the National Health and Nutrition Examination Survey. Vibration-controlled transient elastography was used to assess liver fibrosis and its severity. Neutrophil-to-lymphocyte ratio was calculated as the ratio of neutrophil count to lymphocyte count. RESULTS:  This study included 1620 US adults with a mean age of 52.9 years, of which 53.3% were male. The obese population accounted for 62.5%, 68.5% had hypertension, 31.1% had diabetes, and 16% had significant liver fibrosis. After adjusting for all covariates, a positive correlation was observed between NLR and the severity of liver fibrosis (ß = 0.57, 95% CI = 0.22-0.92, P = .001), which remained stable across different subgroups. CONCLUSION:  This study suggests that elevated NLR levels are positively correlated with the severity of liver fibrosis in patients with nonalcoholic fatty liver disease, and these results can be well generalized to the US adult population.

CLASP-mediated competitive binding in protein condensates directs microtubule growth.

Microtubule organization in cells relies on targeting mechanisms. Cytoplasmic linker proteins (CLIPs) and CLIP-associated proteins (CLASPs) are key regulators of microtubule organization, yet the underlying mechanisms remain elusive. Here, we reveal that the C-terminal domain of CLASP2 interacts with a common motif found in several CLASP-binding proteins. This interaction drives the dynamic localization of CLASP2 to distinct cellular compartments, where CLASP2 accumulates in protein condensates at the cell cortex or the microtubule plus end. These condensates physically contact each other via CLASP2-mediated competitive binding, determining cortical microtubule targeting. The phosphorylation of CLASP2 modulates the dynamics of the condensate-condensate interaction and spatiotemporally navigates microtubule growth. Moreover, we identify additional CLASP-interacting proteins that are involved in condensate contacts in a CLASP2-dependent manner, uncovering a general mechanism governing microtubule targeting. Our findings not only unveil a tunable multiphase system regulating microtubule organization, but also offer general mechanistic insights into intricate protein-protein interactions at the mesoscale level.

Tailoring Heterostructure Growth on Liquid Metal Nanodroplets through Interface Engineering.

Liquid metal (LM) nanodroplets possess intriguing surface properties, thus offering promising potential in chemical synthesis, catalysis, and biomedicine. However, the reaction kinetics and product growth at the surface of LM nanodroplets are significantly influenced by the interface involved, which has not been thoroughly explored and understood. Here, we propose an interface engineering strategy, taking a spontaneous galvanic reaction between Ga0 and AuCl4- ions as a representative example, to successfully modulate the growth of heterostructures on the surface of Ga-based LM nanodroplets by establishing a dielectric interface with a controllable thickness between LM and reactive surroundings. Combining high-resolution electron energy-loss spectroscopy (EELS) analysis and theoretical simulation, it was found that the induced charge distribution at the interface dominates the spatiotemporal distribution of the reaction sites. Employing tungsten oxide (WOx) with varying thicknesses as the demonstrated dielectric interface of LM, Ga@WOx@Au with distinct core-shell-satellite or dimer-like heterostructures has been achieved and exhibited different photoresponsive capabilities for photodetection. Understanding the kinetics of product growth and the regulatory strategy of the dielectric interface provides an experimental approach to controlling the structure and properties of products in LM nanodroplet-involved chemical processes.

Nano-Pulse Treatment Overcomes the Immunosuppressive Tumor Microenvironment to Elicit In Situ Vaccination Protection against Breast Cancer.

We previously reported that nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes, and tumors were harvested at 4-h, 8-h, 1-day, 3-day, 7-day, and 3-month post-treatment intervals for the analysis of frequencies, death, and functional markers of various immune cells in addition to the suppressor function of regulatory T cells (Tregs). NPT was verified to elicit strong in situ vaccination (ISV) against breast cancer and promote both acute and long-term T cell memory. NPT abolished immunosuppressive dominance systemically and in the TME by substantially reducing Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). NPT induced apoptosis in Tregs and TAMs. It also functionally diminished the Treg suppression capacity, explained by the downregulation of activation markers, particularly 4-1BB and TGFß, and a phenotypic shift from predominantly activated (CD44+CD62L-) to naïve (CD44-CD62L+) Tregs. Importantly, NPT selectively induced apoptosis in activated Tregs and spared effector CD4+ and CD8+ T cells. These changes were followed by a concomitant rise in CD8+CD103+ tissue-resident memory T cells and TAM M1 polarization. These findings indicate that NPT effectively switches the TME and secondary lymphatic systems from an immunosuppressive to an immunostimulatory state, allowing cytotoxic T cell function and immune memory formation to eliminate cancer cells and account for the NPT in situ vaccination.

Ultralow Glassy Thermal Conductivity and Controllable, Promising Thermoelectric Properties in Crystalline o-CsCu5S3.

We thoroughly investigated the anharmonic lattice dynamics and microscopic mechanisms of the thermal and electronic transport characteristics in orthorhombic o-CsCu5S3 at the atomic level. Taking into account the phonon energy shifts and the wave-like tunneling phonon channel, we predict an ultralow κL of 0.42 w/mK at 300 K with an extremely weak temperature dependence following ∼T-0.33. These findings agree well with experimental values along with the parallel to the Bridgman growth direction. The κL in o-CsCu5S3 is suppressed down to the amorphous limit, primarily due to the unconventional Cu-S bonding induced by the p-d hybridization antibonding state coupled with the stochastic oscillation of Cs atoms. The nonstandard temperature dependence of κL can be traced back to the critical or dominant role of wave-like tunneling of phonon contributions in thermal transport. Moreover, the p-d hybridization of Cu(3)-S bonding results in the formation of a valence band with "pudding-mold" and high-degeneracy valleys, ensuring highly efficient electron transport characteristics. By properly adjusting the carrier concentration, excellent thermoelectric performance is achieved with a maximum thermoelectric conversion efficiency of 18.4% observed at 800 K in p-type o-CsCu5S3. Our work not only elucidates the anomalous electronic and thermal transport behavior in the copper-based chalcogenide o-CsCu5S3 but also provides insights for manipulating its thermal and electronic properties for potential thermoelectric applications.

Rapid Compensation for Noisy Voluntary Movements in Adults with Primary Tic Disorders.

BACKGROUND: It has been proposed that tics and premonitory urges in primary tic disorders (PTD), like Tourette syndrome, are a manifestation of sensorimotor noise. However, patients with tics show no obvious movement imprecision in everyday life. One reason could be that patients have strategies to compensate for noise that disrupts performance (ie, noise that is task-relevant). OBJECTIVES: Our goal was to unmask effects of elevated sensorimotor noise on the variability of voluntary movements in patients with PTD. METHODS: We tested 30 adult patients with PTD (23 male) and 30 matched controls in a reaching task designed to unmask latent noise. Subjects reached to targets whose shape allowed for variability either in movement direction or extent. This enabled us to decompose variability into task-relevant versus less task-relevant components, where the latter should be less affected by compensatory strategies than the former. In alternating blocks, the task-relevant target dimension switched, allowing us to explore the temporal dynamics with which participants adjusted movement variability to changes in task demands. RESULTS: Both groups accurately reached to targets, and adjusted movement precision based on target shape. However, when task-relevant dimensions of the target changed, patients initially produced movements that were more variable than controls, before regaining precision after several reaches. This effect persisted across repeated changes in the task-relevant dimension across the experiment, and therefore did not reflect an effect of novelty, or differences in learning. CONCLUSIONS: Our results suggest that patients with PTD generate noisier voluntary movements compared with controls, but rapidly compensate according to current task demands. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

miR-539-5p targets BMP2 to regulate Treg activation in B-cell acute lymphoblastic leukemia through TGF-ß/Smads/MAPK.

MicroRNAs (mRNAs) were believed to play an important role in cancers, and this study aimed to explore the mechanism of miRNA regulating Treg in B-cell acute lymphoblastic leukemia (B-ALL). Firstly, the differentially expressed miRNAs and target genes significantly associated with Tregs were screened out by high-throughput sequencing, and their enrichment pathways were analyzed. The binding relationship between miRNA and target genes was further verified, and the effects of miRNA on the proliferation and apoptosis of B-ALL Nalm-6 cells and Treg activation were analyzed. Results showed that differentially expressed miR-539-5p was significantly under-expressed, and its target gene BMP2 was significantly over-expressed in B-ALL, and significantly enriched in the TGF-ß1 pathway. In addition, both miR-539-5p and BMP2 were significantly correlated with Treg activity in B-ALL. In vitro experiments further confirmed that miR-539-5p could directly target BMP2. The low expression of miR-539-5p in B-ALL significantly promoted BMP2 expression to promote the proliferation and inhibit apoptosis of Nalm-6 cells. Furthermore, the high expression of BMP2 in B-ALL could cooperate with TGF-ß1 to promote the activation of human CD4+CD25-T cells to Treg, and significantly activate the TGF-ß/Smads/MAPK pathway. In vivo experiments also confirmed that overexpression of miR-539-5p significantly inhibited BMP2 to suppress Treg activation and Smad1 and Smad2 phosphorylation, and finally inhibit the B-ALL process. In conclusion, miR-539-5p was significantly under-expressed in B-ALL and could target BMP2 to promote its expression, and the overexpressed BMP2 further promoted Treg activation in B-ALL by regulating TGF-ß/Smads/MAPK pathway.

Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.

Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.

Novel room-temperature full-Heusler thermoelectric material Li2TlSb.

High lattice thermal conductivity stemming from the intrinsically ordered crystal and strong interatomic bonds tends to be seen as the bottleneck for achieving excellent thermoelectric properties in full-Heusler (FH) semiconductors. In this work, we propose a novel Li-based FH compound Li2TlSb by substituting one Li atom with a Tl atom in Li3Sb. Then we systematically investigated its transport and thermoelectric properties based on self-consistent phonon (SCP) theory, electron-phonon scattering, and the Boltzmann transport equation. The theoretical calculation confirms that it exhibits outstanding mechanical properties and extreme environment adaptability. Surprisingly, the combination of an unexpectedly high spatial degeneracy and light electron dispersion at valence bands results in a high power factor in p-type systems. Additionally, the rattling behavior governed by the Tl atom and resonant bonding is responsible for ultra-low lattice thermal conductivity with 0.79 W m-1 K-1 at room temperature. Finally, a maximum p-type ZT value of 1.77 at 300 K has been achieved, which surpasses those of most of the traditional thermoelectric (TE) materials. Our results demonstrate that Li2TlSb serves as a potential candidate for room-temperature thermoelectric materials and simultaneously provides new insights for rationally designing novel FH materials in the future.

Changes in Corneal Higher-Order Aberrations and Ocular Biometric Measurements after Phacoemulsification Combined with Goniosynechialysis in Primary Angle Closure/Glaucoma Patients.

Purpose: To compare corneal higher-order aberrations (HOAs), refractive error, and ocular biological parameters before and after phacoemulsification combined with goniosynechialysis (Phaco-GSL) in primary angle closure/glaucoma (PAC/PACG) patients with different axial lengths (ALs). Methods: In this prospective study, cataract patients diagnosed with PAC/PACG were categorized into two groups based on their ALs: the short AL group (AL ≤ 22.5 mm) and the normal AL group (22.5 < AL ≤ 24.5 mm). The pre- and postsurgery measurements of intraocular pressure (IOP) and best-corrected visual acuity (BCVA) were conducted at 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months. Additionally, the assessments included corneal HOAs, the number of antiglaucoma medications, visual field parameters, manifest refraction, and other ocular biological parameters before surgery and at the final follow-up. Results: Prior to surgery, the two groups exhibited no significant differences, except for AL, curvature value, and Z (4, 0) of the posterior corneal surface (all P < 0.01). Following surgery, BCVA improved, and IOP decreased significantly in both groups (P < 0.01). Both anterior and total corneal HOAs, along with Z (3, -3), increased in the two groups (all P < 0.05), with the normal AL group exhibiting a significantly greater increase in total cornea Z (3, -3) than the short AL group (P=0.047). The normal AL group also exhibited a slight tendency towards hyperopia (P < 0.01). Significant changes were observed in the visual field index and mean deviation in both groups (P < 0.05). Conclusions: Phaco-GSL resulted in an increased corneal HOAs, particularly trefoil, with variations based on the patient's AL. Patients with normal ALs tended to shift towards hyperopia after surgery.

Synergistic effects of nanosecond pulsed plasma and electric field on inactivation of pancreatic cancer cells in vitro.

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) in vitro were evaluated on the metabolic activities of cells and transcellular electrical resistance (TER). It was observed that treatment with ns-APPJ for > 2 min disrupts Pan02 cell stability and resulted in over 30% cell death. Similarly, applying nsPEF alone, > 20 pulses resulted in over 15% cell death. While the inactivation activity from the individual treatment is moderate, combined treatments resulted in 80% cell death, approximately 3-to-fivefold increase compared to the individual treatment. In addition, reactive oxygen species such as OH and O were identified at the plasma-liquid interface. The gas temperature of the plasma and the temperature of the cell solution during treatments were determined to be near room temperature.

Mo-doping heterojunction: interfacial engineering in an efficient electrocatalyst for superior simulated seawater hydrogen evolution.

Exploring economical, efficient, and stable electrocatalysts for the seawater hydrogen evolution reaction (HER) is highly desirable but is challenging. In this study, a Mo cation doped Ni0.85Se/MoSe2 heterostructural electrocatalyst, Mox-Ni0.85Se/MoSe2, was successfully prepared by simultaneously doping Mo cations into the Ni0.85Se lattice (Mox-Ni0.85Se) and growing atomic MoSe2 nanosheets epitaxially at the edge of the Mox-Ni0.85Se. Such an Mox-Ni0.85Se/MoSe2 catalyst requires only 110 mV to drive current densities of 10 mA cm-2 in alkaline simulated seawater, and shows almost no obvious degradation after 80 h at 20 mA cm-2. The experimental results, combined with the density functional theory calculations, reveal that the Mox-Ni0.85Se/MoSe2 heterostructure will generate an interfacial electric field to facilitate the electron transfer, thus reducing the water dissociation barrier. Significantly, the heteroatomic Mo-doping in the Ni0.85Se can regulate the local electronic configuration of the Mox-Ni0.85Se/MoSe2 heterostructure catalyst by altering the coordination environment and orbital hybridization, thereby weakening the bonding interaction between the Cl and Se/Mo. This synergistic effect for the Mox-Ni0.85Se/MoSe2 heterostructure will simultaneously enhance the catalytic activity and durability, without poisoning or corrosion of the chloride ions.

Correlation between chronic low-grade inflammation and glucose and lipid metabolism indicators in polycystic ovary syndrome.

OBJECTIVE: The purpose of this study was to explore the correlation between inflammatory indicators and blood lipids and to further provide a theoretical basis for the diagnosis and treatment of clinical polycystic ovary syndrome (PCOS). METHODS: Whole-blood cell counts and hormone and blood lipid levels were measured in 110 patients with PCOS and 126 healthy women. The differences in the above levels and the correlation between inflammation and blood lipid levels in the two groups were determined, and classified according to BMI. Differences in inflammatory indices were also analyzed. The independent risk factors for PCOS were analyzed by binary logistic regression. RESULTS: The PCOS group had greater BMI and greater body weight than the control group. The inflammatory indicators WBC, neutrophil, lymphocyte, monocyte counts and the NLR were significantly higher than those of the control group. It had higher testosterone (TSTO), triglyceride (TG) and total cholesterol (TC) levels. Correlation analysis showed that leukocyte and neutrophil counts were positively correlated with TSTO and TG levels and negatively correlated with HDL. In the BMI ≥ 24 and BMI < 24 groups, WBC was higher in PCOS patients than in healthy controls. Logistic regression showed that TSTO, TG and FSH were independent risk factors for PCOS. CONCLUSION: Inflammatory markers are correlated with blood lipids in PCOS. During the treatment of PCOS, blood lipids and serum inflammatory factors should be monitored.

Synthesis of taste active γ-glutamyl peptides with pea protein hydrolysate and their taste mechanism via in silico study.

Pea (Pisum sativum L.) protein hydrolysate (PPH) has a bitter taste, which has limited its use in food industry. γ-Glutamylation is used to debitter PPH. Results showed that the bitterness of PPH was decreased significantly due to the formation of γ-glutamyl peptides, including 16 γ-[Glu](n=1/2)-amino acids (AAs) and 8 newly discovered γ-glutamyl tripeptides (γ-Glu-Asn-Phe, γ-Glu-Leu-Val, γ-Glu-Leu-Tyr, γ-Glu-Gly-Leu, γ-Glu-Gly-Phe, γ-Glu-Gly-Tyr, γ-Glu-Val-Val, and γ-Glu-Gln-Tyr). Their total production concentrations were 27.25 µmol/L and 77.76 µmol/L, respectively. The γ-Glu-AA-AAs presented an umami-enhancing, salty-enhancing, and kokumi taste when their concentration reached 1.67 ± 0.20 âˆ¼ 2.07 ± 0.20, 1.65 ± 0.25 âˆ¼ 2.29 ± 0.45 and 0.68 ± 0.19 âˆ¼ 1.03 ± 0.22 mmol/L, respectively. The γ-Glu-AA-AAs exhibited a kokumi taste by entering the Venus flytrap (VFT) of the calcium-sensing receptor and interacting with Ser147, Ala168, and Ser170. γ-Glu-AA-AAs can enhance the umaminess of Monosodium Glutamate (MSG) as they can enter the binding pocket of the taste receptor type 1 subunit 3 (T1R3)-MSG complex.

Relict Plants Are Better Able to Adapt to Climate Change: Evidence from Desert Shrub Communities.

Shrubs are the main dominant plants in arid desert systems and play an important role in maintaining the biodiversity, ecosystem services and stability of desert ecosystems. Studies have shown that the survival of a large number of shrub species in desert areas under the influence of climate change is significantly threatened, with different species showing different response strategies. To test the tolerance of different shrub species to climate change, this study selected 10 dominant shrub species (ancient relict shrub species and regional endemic shrub species) in the Alashan desert area as the research object. Based on a field survey of species distribution, a species distribution model was developed to simulate the suitable distribution area of shrub species under current conditions and under future climate change scenarios. The distribution changes of ancient relict and regional endemic shrub species under the climate change scenarios were tested, and the tolerance of the two types of shrub to climate change was analyzed. The results showed that under different climate change scenarios, except for Ammopiptanthus mongolicus, the total suitable area of four out of the five relict plants was relatively stable, the potential distribution area of Tetraena mongolica increased, and the future distribution pattern was basically consistent with the current distribution. However, the suitable area of typical desert plants was unstable under different climate change scenarios. Except for Kalidium foliatum, the suitable distribution areas of four out of the five shrubs showed different degrees of reduction, and the distribution location showed significant migration. Based on the research results, climate change will lead to the reduction and displacement of the distribution area of typical desert shrubs, while relict shrubs will be less affected by climate change. This is because, compared to desert species, relict plants have a longer evolutionary history and have developed a wider range of adaptations after experiencing dramatic environmental changes. This study provides a scientific basis for actively responding to the impacts of climate change on desert ecosystems.

The contribution of inoculated probiotics to increased protein-derived volatile flavor compounds.

This study aimed to evaluate the contribution and mechanisms of Lactobacillus plantarum and Zygosaccharomyces mellis inoculation to the enhancement of protein-derived volatile flavor compounds (PVFCs) in low-salt dry-cured mackerel (LDCM). The contents of PVFCs (3-methylbutanal and phenylacetaldehyde), intermediates (α-ketoisocaproate and phenylpyruvic acid), precursor (α-ketoisocaproate and phenylpyruvic acid), and key enzyme activities (protease and transaminase) significantly increased (p < 0.05) in probiotic-treated groups. The dominant species in the probiotics-treated groups were the inoculated Lactobacillus plantarum and Zygosaccharomyces mellis, which were the main producer of key enzymes for the generation of PVFCs. Lactobacillus plantarum performed well in protein degradation and amino acid transamination, resulting in generating more 3-methylbutanal and phenylacetaldehyde, while Zygosaccharomyces mellis played a main role in phenylethanol production. The synergistic action of Lactobacillus plantarum and Zygosaccharomyces mellis could promote the formation of 3-methyl-1-butanol.

Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.