Language-Guided 3-D Action Feature Learning Without Ground-Truth Sample Class Label.

This work pays the first research effort to leverage point cloud sequence-based Self-supervised 3-D Action Feature Learning (S3AFL), under text's cross-modality weak supervision. We intend to fill the huge performance gap between point cloud sequence and 3-D skeleton-based manners. The key intuition derives from the observation that skeleton-based manners actually hold the human pose's high-level knowledge that leads to attention on the body's joint-aware local parts. Inspired by this, we propose to introduce the text's weak supervision of high-level semantics into a point cloud sequence-based paradigm. With RGB-point cloud pair sequence acquired via RGB-D camera, text sequence is first generated from RGB component using pretrained image captioning model, as auxiliary weak supervision. Then, S3AFL runs in a cross and intra-modality contrastive learning (CL) way. To resist text's missing and redundant semantics, feature learning is conducted in a multistage way with semantic refinement. Essentially, text is only required for training. To facilitate the feature's representation power on fine-grained actions, a multirank max-pooling (MR-MP) way is also proposed for the point set network to better maintain discriminative clues. Experiments verify that the text's weak supervision can facilitate performance by 10.8%, 10.4%, and 8.0% on NTU RGB + D 60, 120, and N-UCLA at most. The performance gap between point cloud sequence and skeleton-based manners has been remarkably narrowed down. The idea of transferring text's weak supervision to S3AFL can also be applied to a skeleton manner, with strong generality. The source code is available at https://github.com/tangent-T/W3AMT.

Bromine Radical (Br• and Br2•-) Reactivity with Dissolved Organic Matter and Brominated Organic Byproduct Formation.

Dissolved organic matter (DOM) is a major scavenger of bromine radicals (e.g., Br• and Br2•-) in sunlit surface waters and during oxidative processes used in water treatment. However, the literature lacks quantitative measurements of reaction rate constants between bromine radicals and DOM and lacks information on the extent to which these reactions form brominated organic byproducts. Based on transient kinetic analysis with different fractions and sources of DOM, we determined reaction rate constants for DOM with Br• ranging from <5.0 × 107 to (4.2 ± 1.3) × 108 MC-1 s-1, which are comparable with those of HO• but higher than those with Br2•- (k = (9.0 ± 2.0) × 104 to (12.4 ± 2.1) × 105 MC-1 s-1). Br• and Br2•- attack the aromatic and antioxidant moieties of DOM via the electron transfer mechanism, resulting in Br- release with minimal substitution of bromine into DOM. For example, the total organic bromine was less than 0.25 µM (as Br) at environmentally relevant bromine radicals' exposures of ∼10-9 M·s. The results give robust evidence that the scavenging of bromine radicals by DOM is a crucial step to prevent inorganic bromine radical chemistry from producing free bromine (HOBr/OBr-) and subsequent brominated byproducts.

Exosomal miR-30d-5p of neutrophils induces M1 macrophage polarization and primes macrophage pyroptosis in sepsis-related acute lung injury.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) play an important role in sepsis-related acute lung injury (ALI). Accumulating evidence suggests PMN-derived exosomes as a new subcellular entity acting as a fundamental link between PMN-driven inflammation and tissue damage. However, the role of PMN-derived exosomes in sepsis-related ALI and the underlying mechanisms remains unclear. METHODS: Tumor necrosis factor-α (TNF-α), a key regulator of innate immunity in sepsis-related ALI, was used to stimulate PMNs from healthy C57BL/6J mice in vitro. Exosomes isolated from the supernatant were injected to C57BL/6J wild-type mice intraperitoneally (i.p.) and then examined for lung inflammation, macrophage (Mϕ) polarization and pyroptosis. In vitro co-culture system was applied where the mouse Raw264.7 macrophages or bone marrow-derived macrophages (BMDMs) were co-cultured with PMN-derived exosomes to further confirm the results of in vivo animal study and explore the potential mechanisms involved. RESULTS: Exosomes released by TNF-α-stimulated PMNs (TNF-Exo) promoted M1 macrophage activation after in vivo i.p. injection or in vitro co-culture. In addition, TNF-Exo primed macrophage for pyroptosis by upregulating NOD-like receptor 3 (NLRP3) inflammasome expression through nuclear factor κB (NF-κB) signaling pathway. Mechanistic studies demonstrated that miR-30d-5p mediated the function of TNF-Exo by targeting suppressor of cytokine signaling (SOCS-1) and sirtuin 1 (SIRT1) in macrophages. Furthermore, intravenous administration of miR-30d-5p inhibitors significantly decreased TNF-Exo or cecal ligation and puncture (CLP)-induced M1 macrophage activation and macrophage death in the lung, as well as the histological lesions. CONCLUSIONS: The present study demonstrated that exosomal miR-30d-5p from PMNs contributed to sepsis-related ALI by inducing M1 macrophage polarization and priming macrophage pyroptosis through activating NF-κB signaling. These findings suggest a novel mechanism of PMN-Mϕ interaction in sepsis-related ALI, which may provide new therapeutic strategies in sepsis patients.

Driving Pressure-Guided Individualized Positive End-Expiratory Pressure in Abdominal Surgery: A Randomized Controlled Trial.

BACKGROUND: The optimal positive end-expiratory pressure (PEEP) to prevent postoperative pulmonary complications (PPCs) remains unclear. Recent evidence showed that driving pressure was closely related to PPCs. In this study, we tested the hypothesis that an individualized PEEP guided by minimum driving pressure during abdominal surgery would reduce the incidence of PPCs. METHODS: This single-centered, randomized controlled trial included a total of 148 patients scheduled for open upper abdominal surgery. Patients were randomly assigned to receive an individualized PEEP guided by minimum driving pressure or an empiric fixed PEEP of 6 cm H2O. The primary outcome was the incidence of clinically significant PPCs within the first 7 days after surgery, using a χ2 test. Secondary outcomes were the severity of PPCs, the area of atelectasis, and pleural effusion. Other outcomes, such as the incidence of different types of PPCs (including hypoxemia, atelectasis, pleural effusion, dyspnea, pneumonia, pneumothorax, and acute respiratory distress syndrome), intensive care unit (ICU) admission rate, length of hospital stay, and 30-day mortality were also explored. RESULTS: The median value of PEEP in the individualized group was 10 cm H2O. The incidence of clinically significant PPCs was significantly lower in the individualized PEEP group compared with that in the fixed PEEP group (26 of 67 [38.8%] vs 42 of 67 [62.7%], relative risk = 0.619, 95% confidence intervals, 0.435-0.881; P = .006). The overall severity of PPCs and the area of atelectasis were also significantly diminished in the individualized PEEP group. Higher respiratory compliance during surgery and improved intra- and postoperative oxygenation was observed in the individualized group. No significant differences were found in other outcomes between the 2 groups, such as ICU admission rate or 30-day mortality. CONCLUSIONS: The application of individualized PEEP based on minimum driving pressure may effectively decrease the severity of atelectasis, improve oxygenation, and reduce the incidence of clinically significant PPCs after open upper abdominal surgery.

Platelet-derived exosomes promote neutrophil extracellular trap formation during septic shock.

BACKGROUND: Platelets have been demonstrated to be potent activators of neutrophil extracellular trap (NET) formation during sepsis. However, the mediators and molecular pathways involved in human platelet-mediated NET generation remain poorly defined. Circulating plasma exosomes mostly originating from platelets may induce vascular apoptosis and myocardial dysfunction during sepsis; however, their role in NET formation remains unclear. This study aimed to detect whether platelet-derived exosomes could promote NET formation during septic shock and determine the potential mechanisms involved. METHODS: Polymorphonuclear neutrophils (PMNs) were cocultured with exosomes isolated from the plasma of healthy controls and septic shock patients or the supernatant of human platelets stimulated ex vivo with phosphate buffer saline (PBS) or lipopolysaccharide (LPS). A lethal cecal ligation and puncture (CLP) mouse model was used to mimic sepsis in vivo; then, NET formation and molecular pathways were detected. RESULTS: NET components (dsDNA and MPO-DNA complexes) were significantly increased in response to treatment with septic shock patient-derived exosomes and correlated positively with disease severity and outcome. In the animal CLP model, platelet depletion reduced plasma exosome concentration, NET formation, and lung injury. Mechanistic studies demonstrated that exosomal high-mobility group protein 1 (HMGB1) and/or miR-15b-5p and miR-378a-3p induced NET formation through the Akt/mTOR autophagy pathway. Furthermore, the results suggested that IκB kinase (IKK) controls platelet-derived exosome secretion in septic shock. CONCLUSIONS: Platelet-derived exosomes promote excessive NET formation in sepsis and subsequent organ injury. This finding suggests a previously unidentified role of platelet-derived exosomes in sepsis and may lead to new therapeutic approaches.

A Fluorescently Ratiometric Natural Probe for Selective Detection of Sulfur Dioxide Derivative and Host-Guest Supramolecular Regulation.

Natural sanguinarine (SG) was first used as a fluorescent probe to develop a novel ratiometric sensor for selective HSO3- detection. The nucleophilic addition reaction of HSO3- occurs at the C=N+ group of SG, and subsequent breakage of the conjugated π cycle leads to a decrease in the SG iminium fluorescence that is accompanied by an increase in the alkanolamine fluorescence. Therefore, a ratiometric fluorescence method with a large wavelength shift can be established for HSO3- detection. Furthermore, cucurbit[8]uril was used as an efficient host to encapsulate SG for an improved selectivity for HSO3- detection over H2S. Our method benefits include little interference from other common anions and cations for HSO3- detection, suggesting a promising application in real sample analysis. Besides sensor development, the interaction of the natural SG with HSO3- was first demonstrated in this work to further get an insight into SG's pharmacology.

Intraoperative monitoring of nociception for opioid administration: a meta-analysis of randomized controlled trials.

INTRODUCTION: Under-dosage or over-dosage of intraoperative analgesia can cause harm to patients. Many studies have demonstrated the clinical advantages of nociception monitoring tools, but with some conflicting results. To clarify the issue, this meta-analysis compared the effects of Analgesia Nociception Index (ANI), Surgical Pleth Index (SPI), and pupillometry monitoring methods with those of analgesia management practices of intraoperative opioid administration. EVIDENCE ACQUISITION: A comprehensive literature search was conducted to identify clinical trials that compared the effect of monitoring of nociception-antinociception balance (versus clinical signs) on intraoperative opioid administration. Meta-analysis was performed for intraoperative opioid administration, postoperative pain and rescue opioid consumption separately using fixed-effects model and random effects model. In addition, a subgroup analysis was also performed to determine the effects of age, study quality, anesthesia regimen, and nociception monitoring devices on intraoperative opioid administration. EVIDENCE ANALYSIS: Ten studies that used ANI, SPI, or pupillometry for intraoperative opioid guidance were identified. As a principle finding, nociception measurement-guided analgesia reduced intraoperative opioid consumption compared with conventional analgesia. In adults, SPI-guided intraoperative opioid administration was lower than conventional analgesia, whereas the difference between ANI-guided analgesia and standard clinical care was not statistically significant. Furthermore, in adults, anesthetized with sevoflurane, nociception monitoring decreased intraoperative analgesia doses. CONCLUSIONS: Nociception monitoring devices seem to have an advantage over standard clinical practice on intraoperative management of analgesia during general anesthesia. Future research should focus on identifying appropriate indicators to objectively assess the degree of pain in children and perform large-scale multicenter trials to prove clinical advantages of nociception measurements during propofol anesthesia.

Target-switched triplex nanotweezer and synergic fluorophore translocation for highly selective melamine assay.

This paper describes a triplex DNA nanotweezer to specifically capture melamine (MEL). The triplex-forming oligonucleotide (TFO) arm can be switched from the open state to the closed state once MEL binds to the abasic site (AP site) in duplex via the bifacial hydrogen bonding with thymines. Following this nanotweezer operation, the AP site-bound fluorophore is translocated to the terminal triplet to subsequently light up the nanotweezer. The TFO arm is found to be pivotal for permitting the AP site binding. The synergic processes of target competition and fluorophore translocation support a high selectivity for the MEL assay even against the inherent adenosine and the MEL hydrolysis products. Chelerythrine is employed as the fluorescent probe. The detection limit of MEL was estimated to be about 140 nM assuming a signal-to-noise ratio of 3. It was applied to the determination of MEL in spiked milk samples without any separation procedure. Conceivably, this method opens a new avenue towards highly selective triplex-based sensors by making use of other commercially available DNA modifications for recognizing other analytes. Graphical abstract Schematic presentation of a triplex nanotweezer with an open-to-close conversion upon the abasic site binding of melamine. The assay is based on a synergic fluorophore translocation. The corresponding duplex otherwise shows no binding with melamine. Chelerythrine (CHE) with a yellow-green emission peaking at 544 nm is employed as the fluorescent probe.

Supramolecularly Multicolor DNA Decoding Using an Indicator Competition Assay.

Relative to the individual intensity-dependent strategy, the multicolor fluorescence sensor has promise to achieve a high signaling contrast. In this work, we develop a cucurbituril-based supramolecular and multicolor DNA recognition rationale via indicator competition assay (ICA). Alkaloids of coptisine (COP) and palmatine (PAL) are identified as the proof-of-principle indicators with a lighting-up fluorescence upon supramolecular complexation to cucurbit[7]uril (CB[7]). With an introduced abasic site (AP site) as the contestant, DNAs having pyrimidines opposite this site can compete for COP with CB[7] to bring an emission color change from green to yellow brown, while those having purines opposite the AP site do not compete for COP and still have the green emission, indicative of a high selectivity for the multicolor nucleotide transversion recognition. However, because of the relatively weaker binding of PAL with CB[7], the AP site-containing DNA can take away PAL from its CB[7] complex and resultantly bring a blue-to-green emission color change independent of the AP site-opposite nucleotide identity, dissimilar to the remaining blue color for the fully matched DNA without the AP site, suggesting a preferable strategy for the AP site biomarker detection. Our method demonstrates a new way to develop an ICA-based multicolor DNA sensor with the supramolecular cucurbituril complexation to ensure a highly selective performance.

Insights into the interactions between tetracycline, its degradation products and bovine serum albumin.

Tetracyclines (TCs) are the most widely used antibiotics in the world. Because antibiotics have low bioavailability and are difficult to completely remove using current sewage treatment facilities, residual TCs and their degradation products in the environment, animal and plant foodstuffs and personal care products may enter the body through the food chain, thus causing unpredictable effects on human health. We studied bovine serum albumin (BSA) (a functional protein) as a target of tetracycline-induced toxicity by examining its interactions with TC, anhydrotetracycline (ATC) and epitetracycline (ETC), based on a fluorescence spectroscopy and molecular docking method under simulated physiological conditions. The interaction mechanism was elucidated at the molecular level. The results show that TC, ATC and ETC bind at site II of BSA and interact mainly through hydrogen bonding interactions and van der Waals interactions. The binding affinities can be ranked in the order ATC > TC > ETC.