Purple non-sulfur bacteria technology: a promising and potential approach for wastewater treatment and bioresources recovery.

Shortage of water, energy, and bioresources in the world has led to the exploration of new technologies that achieve resource recovery from wastewater, which has become a new sustainable trend. Photosynthetic non-sulfur bacteria (PNSB), the most ancient photo microorganism, not only treats different wastewater types, but also generates PNSB cells, which are non-toxic bioresources and containing many value-added products. These bioresources can be used as raw materials in the agricultural, food, and medical industries. Therefore, PNSB or PNSB-based wastewater resource recovery technology can be simultaneously used to treat wastewater and produce useful bioresources. Compared with traditional wastewater treatment, this technology can reduce CO2 emissions, promote the N recovery ratio and prevent residual sludge disposal or generation. After being developed for over half a century, PNSB wastewater resource recovery technology is currently extended towards industrial applications. Here, this technology is comprehensively introduced in terms of (1) PNSB characteristics and metabolism; (2) PNSB wastewater treatment and bioresource recovery efficiency; (3) the relative factors influencing the performance of this technology, including light, oxygen, strains, wastewater types, hydraulic retention time, on wastewater treatment, and resource production; (4) PNSB value-added bioresources and their generation from wastewater; (5) the scale-up history of PNSB technology; (6) Finally, the future perspectives and challenges of this technology were also analysed and summarised.

Experimental evidence refuting the assumption of phosphorus-31 nuclear-spin entanglement-mediated consciousness.

Phosphorus-31 nuclear-spin entanglements within Ca9(PO4)6 molecules (Posner molecules) have been proposed to be central for neural processing. However, this has yet to be proven experimentally. Relatedly, increasing calcium ion concentration in the cerebrospinal fluid has been proposed to enhance consciousness by accelerating Posner molecules' creation. A dependence on calcium isotope is also expected. Here we test these predictions experimentally by measuring the loss of righting reflex ED50 for mice to sevoflurane - an increase in loss of righting reflex ED50 indicates a higher level of consciousness and vice versa. Our mice's findings demonstrate that intracerebroventricular injection of EGTA enhances the sevoflurane-induced loss of righting reflex ED50 while injecting calcium-40 chloride or calcium-43 chloride causes an opposite effect. Further, the identical effects of calcium-40 and calcium-43 indicate an absence of calcium isotope dependence. Here, our findings disprove conventional proposals that calcium ion concentration correlates with consciousness.

Synthesis and Preliminary Anticancer Evaluation of 4-C Derivatives of Diphyllin.

The natural lignan diphyllin has shown promising antitumor activity, although its clinical advancement has been impeded by challenges such as low solubility, poor metabolic stability, and limited potency. In response, we developed and synthesized two sets of diphyllin 4-C derivatives, comprising six ester derivatives and eight 1, 2, 3-triazole derivatives. Notably, among these derivatives, 1, 2, 3-triazole derivatives 7c and 7e demonstrated the most potent cytotoxic effects, with IC50 values ranging from 0.003 to 0.01 µM. Treatment with 0.2 µM of 7c and 7e resulted in a reduction of V-ATPase activity in HGC-27 cells to 23% and 29%, respectively.

Getah virus Nsp3 binds G3BP to block formation of bona fide stress granules.

Stress granules (SGs) are cytoplasmic aggregates of proteins and mRNA that form in response to diverse environmental stressors, including viral infections. Several viruses possess the ability to block the formation of stress granules by targeting the SGs marker protein G3BP. However, the molecular functions and mechanisms underlying the regulation of SGs formation by Getah virus (GETV) remain unclear. In this study, we found that GETV infection triggered the formation of Nsp3-G3BP aggregates, which differed in composition from SGs. Further studies revealed that the presence of these aggregates was dependent on the activation of the PKR/eIF2α signaling pathway. Interestingly, we found that Nsp3 HVD domain blocked the formation of SGs by binding to G3BP NTF2 domain. Moreover, knockout of G3BP in NCI-H1299 cells had no effect on GETV replication, while overexpression of G3BP to form the genuine SGs significantly inhibited GETV replication. Overall, our study elucidates a novel role GETV Nsp3 to change the composition of SG as well as cellular stress response.

A Cyclic Peptide Based on Pheasant Cathelicidin Inhibits Influenza A H1N1 Virus Infection.

Influenza viruses are the leading cause of upper respiratory tract infections, leading to several global pandemics and threats to public health. Due to the continuous mutation of influenza A viruses, there is a constant need for the development of novel antiviral therapeutics. Recently, natural antimicrobial peptides have provided an opportunity for the discovery of anti-influenza molecules. Here, we designed several peptides based on pheasant cathelicidin and tested their antiviral activities and mechanisms against the H1N1 virus. Of note, the designed peptides Pc-4 and Pc-5 were found to inhibit replication of the H1N1 virus with an IC50 = 8.14 ± 3.94 µM and 2.47 ± 1.95 µM, respectively. In addition, the cyclic peptide Pc-5 was found to induce type I interferons and the expression of interferon-induced genes. An animal study showed that the cyclic peptide Pc-5 effectively inhibited H1N1 virus infection in a mouse model. Taken together, our work reveals a strategy for designing cyclic peptides and provides novel molecules with therapeutic potential against influenza A virus infection.

Synthesis of intramolecular cross-coupling analogues of forskolin.

A ring distortion strategy was applied to the synthesis of a series of intramolecular cross-coupled analogues of forskolin 1. Treatment with palladium acetate, forskolin underwent an intramolecular cross-coupling reaction to generate a novel cycloalkene ether 2 in 85% yield. Under the same conditions, a series of forskolin ester analogues 4a-4d were prepared from 1-OH ester derivatives of forskolin 3a-3d in 85-93% yields. Treating cycloalkene ether 2 with aryl iodides in the presence of a palladium catalyst afforded Z-isomers arylation products 5a-5e in a stereoselective manner in 70-85% yields.

The Amorphous Solid Dispersion of Chrysin in Plasdone® S630 Demonstrates Improved Oral Bioavailability and Antihyperlipidemic Performance in Rats.

Chrysin is a flavonoid with various biological activities. However, its low water solubility and strong metabolism render its oral bioavailability rather poor. This study aimed to develop a stable solid dispersion formulation of chrysin to improve the dissolution of chrysin, so as to increase its oral bioavailability and improve its antihyperlipidemic activities. A solid dispersion of chrysin was prepared using a solvent evaporation method, with Plasdone® S630 as the hydrophilic carrier. The formulations were characterized via X-ray diffraction, in vitro dissolution studies, and stability studies. An in-situ perfusion model was used to evaluate the absorption rates. Plasma pharmacokinetics and antihyperlipidemic performance after the oral administration of the chrysin formulations were investigated in rats. It was found that the solid dispersion of chrysin prepared using the drug-polymer mass ratio of 1:6 can form the optimized formulation. X-ray diffraction results showed that the chrysin was in an amorphous state in this optimized formulation. The cumulative release percentage of the optimized solid dispersion of chrysin at pH 1.2 and pH 6.8 was elevated to above 90% within 24 h, indicating that the formulation could enhance the dissolution rates of chrysin. Stability studies showed that the optimized formulation presented acceptable long-term storage stability, but it was susceptible to high temperature and humidity. The solid dispersion of chrysin showed higher absorption rates in the in-situ perfusion model. Pharmacokinetic studies revealed that Cmax and AUC after the intragastric administration of solid dispersion of chrysin were appreciably higher than those resulting from chrysin suspension. The oral bioavailability of the solid dispersion of chrysin was 41 times higher than that of chrysin suspension. Pharmacological studies suggested that the solid dispersion of chrysin was more powerful than chrysin raw material in improving biochemical indicators in the hyperlipidemic model in rats. This study reveals the potential use of a novel oral formulation of chrysin to reduce the currently required high dose.

Momentum Contrastive Voxel-wise Representation Learning for Semi-supervised Volumetric Medical Image Segmentation.

Contrastive learning (CL) aims to learn useful representation without relying on expert annotations in the context of medical image segmentation. Existing approaches mainly contrast a single positive vector (i.e., an augmentation of the same image) against a set of negatives within the entire remainder of the batch by simply mapping all input features into the same constant vector. Despite the impressive empirical performance, those methods have the following shortcomings: (1) it remains a formidable challenge to prevent the collapsing problems to trivial solutions; and (2) we argue that not all voxels within the same image are equally positive since there exist the dissimilar anatomical structures with the same image. In this work, we present a novel Contrastive Voxel-wise Representation Learning (CVRL) method to effectively learn low-level and high-level features by capturing 3D spatial context and rich anatomical information along both the feature and the batch dimensions. Specifically, we first introduce a novel CL strategy to ensure feature diversity promotion among the 3D representation dimensions. We train the framework through bi-level contrastive optimization (i.e., low-level and high-level) on 3D images. Experiments on two benchmark datasets and different labeled settings demonstrate the superiority of our proposed framework. More importantly, we also prove that our method inherits the benefit of hardness-aware property from the standard CL approaches. Codes will be available soon.

SimCVD: Simple Contrastive Voxel-Wise Representation Distillation for Semi-Supervised Medical Image Segmentation.

Automated segmentation in medical image analysis is a challenging task that requires a large amount of manually labeled data. However, most existing learning-based approaches usually suffer from limited manually annotated medical data, which poses a major practical problem for accurate and robust medical image segmentation. In addition, most existing semi-supervised approaches are usually not robust compared with the supervised counterparts, and also lack explicit modeling of geometric structure and semantic information, both of which limit the segmentation accuracy. In this work, we present SimCVD, a simple contrastive distillation framework that significantly advances state-of-the-art voxel-wise representation learning. We first describe an unsupervised training strategy, which takes two views of an input volume and predicts their signed distance maps of object boundaries in a contrastive objective, with only two independent dropout as mask. This simple approach works surprisingly well, performing on the same level as previous fully supervised methods with much less labeled data. We hypothesize that dropout can be viewed as a minimal form of data augmentation and makes the network robust to representation collapse. Then, we propose to perform structural distillation by distilling pair-wise similarities. We evaluate SimCVD on two popular datasets: the Left Atrial Segmentation Challenge (LA) and the NIH pancreas CT dataset. The results on the LA dataset demonstrate that, in two types of labeled ratios (i.e., 20% and 10%), SimCVD achieves an average Dice score of 90.85% and 89.03% respectively, a 0.91% and 2.22% improvement compared to previous best results. Our method can be trained in an end-to-end fashion, showing the promise of utilizing SimCVD as a general framework for downstream tasks, such as medical image synthesis, enhancement, and registration.

Periodic oxygen supplementation drives efficient metabolism for enhancing valuable bioresource production in photosynthetic bacteria wastewater treatment.

Periodic oxygen supplementation (A-O) strategy was proposed to improve pollutant removal and enhance bioresource production of photosynthetic bacteria (PSB). The A-O strategy obtained higher COD (91.4%) and NH4+-N (78.6%) removal compared with the non-oxygen supplementation (N-O) strategy, which was similar to the continuous oxygen supplementation (C-O) strategy. A-O strategy achieved the highest biomass concentration of 1338.5 mg/L. Bacteriochlorophyll and carotenoids concentration in the A-O strategy were 24.9-31.1% and 15.1-23.7% higher than those in the other two strategies; coenzyme Q10 concentration and content were 52.5% and 21.3% higher than that in the N-O strategy. The metabolomic analysis showed that the A-O strategy enhanced the tricarboxylic acid cycle after fumaric acid formation and ß-alanine metabolism, then caused higher biomass accumulation. The A-O strategy reduced the inhibition of photophosphorylation by oxidative-phosphorylation and maintained both characteristics. Hence, A-O might be an economic strategy for enhancing pollutant removal and bioresource production in PSB-based wastewater treatment.

Flashing light alleviates photoinhibition and promotes biomass concentration in purple non- sulfur bacteria wastewater treatment.

High light is beneficial for purple non-sulfur bacteria (PNSB) growth. However, excessive light causes photoinhibition. In this novel study, flashing light was used to alleviate photoinhibition and promote biomass growth in PNSB wastewater treatment. Results showed that flashing light effectively increased biomass production. The highest biomass concentration (2688.8 mg/L) and chemical oxygen demand removal (in 177 µmol/m2/s-0.75 duty cycle-1000 Hz group) were 41.5% and 28.4% higher than that in the constant stress light group (same incident light). This group also increased biomass concentration by 21.3% and reduced energy consumption by 26.2% compared with the constant normal light group (same energy input). The shortened single light provision time of flashing light increased the relative electron transportation rate by 116.6%, avoiding photoinhibition, promoting energy utilisation, and enhancing substance synthesis. Flashing light can be used as a light regulation strategy to enhance biomass accumulation and reduce energy consumption in PNSB-based industries.

Class-Aware Adversarial Transformers for Medical Image Segmentation.

Transformers have made remarkable progress towards modeling long-range dependencies within the medical image analysis domain. However, current transformer-based models suffer from several disadvantages: (1) existing methods fail to capture the important features of the images due to the naive tokenization scheme; (2) the models suffer from information loss because they only consider single-scale feature representations; and (3) the segmentation label maps generated by the models are not accurate enough without considering rich semantic contexts and anatomical textures. In this work, we present CASTformer, a novel type of adversarial transformers, for 2D medical image segmentation. First, we take advantage of the pyramid structure to construct multi-scale representations and handle multi-scale variations. We then design a novel class-aware transformer module to better learn the discriminative regions of objects with semantic structures. Lastly, we utilize an adversarial training strategy that boosts segmentation accuracy and correspondingly allows a transformer-based discriminator to capture high-level semantically correlated contents and low-level anatomical features. Our experiments demonstrate that CASTformer dramatically outperforms previous state-of-the-art transformer-based approaches on three benchmarks, obtaining 2.54%-5.88% absolute improvements in Dice over previous models. Further qualitative experiments provide a more detailed picture of the model's inner workings, shed light on the challenges in improved transparency, and demonstrate that transfer learning can greatly improve performance and reduce the size of medical image datasets in training, making CASTformer a strong starting point for downstream medical image analysis tasks.

CtD strategy to construct stereochemically complex and structurally diverse compounds from griseofulvin.

The Complexity to Diversity (CtD) strategy, a strategy for the synthesis of stereochemically complex and structurally diverse small molecules from natural products using ring-distortion reactions, was applied in the synthesis of a 47-member compound collection from the natural product griseofulvin. A Tsuji-Trost allylation and oxa-Michael cyclization tandem reaction was used for the first time in the CtD strategy to generate complex ring fused compounds.

An Endogenous Retroviral LTR-Derived Long Noncoding RNA lnc-LTR5B Interacts With BiP to Modulate ALV-J Replication in Chicken Cells.

Infection with the avian leukosis virus subgroup J (ALV-J) impairs host genes and facilitates the establishment of chronic infection and the viral life cycle. However, the involvement of long noncoding RNAs (lncRNAs) in ALV-J infection remains largely unknown. In this study, we identified a novel chicken lncRNA derived from LTR5B of the ERV-L family (namely lnc-LTR5B), which is significantly downregulated in ALV-J infected cells. lnc-LTR5B was localized in the cytoplasm and was relatively high expressed in the chicken lung and liver. Notably, the replication of ALV-J was inhibited by the overexpression of lnc-LTR5B but enhanced when lnc-LTR5B expression was knocked down. We further confirmed that lnc-LTR5B could bind to the binding immunoglobulin protein (BiP), a master regulator of endoplasmic reticulum (ER) function. Mechanistically, lnc-LTR5B serves as a competing endogenous RNA for BiP, restricting its physical availability. Upon ALV-J infection, the reduction of lnc-LTR5B released BiP, which facilitated its translocation to the cell surface. This is crucial for ALV-J entry as well as pro-survival signaling. In conclusion, we identified an endogenous retroviral LTR-activated lnc-LTR5B that is involved in regulating the cell surface translocation of BiP, and such regulatory machinery can be exploited by ALV-J to complete its life cycle and propagate.

Targeting the Histone Methyltransferase Disruptor of Telomeric Silencing 1-Like Restricts Avian Leukosis Virus Subgroup J Replication by Restoring the Innate Immune Response in Chicken Macrophages.

Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, is known to cause immunosuppression and various types of cancer in chickens. Recent reports have shown that epigenetic changes in DNA and chromatin are widely implicated in the life cycle of diverse viruses, and reversal of these changes in host cells can lead to alterations in the propagation of viruses. In the present study, we found that disruptor of telomeric silencing 1-like (DOT1L), a histone H3 lysine79 (H3K79) methyltransferase, was upregulated during ALV-J infection in chicken macrophage HD11 cells. Subsequently, we show that targeting DOT1L with a specific inhibitor can significantly decrease the ALV-J replication and viral production. By generating of DOT1L-knockout (KO) HD11 cells using the CRISPR/Cas9 system, we show that deletion of the DOT1L led to an increase in the induction of IFNß and interferon-stimulated genes (ISGs) in HD11 cells in response to ALV-J infection. Importantly, we confirmed that ALV-J infection impaired the activation of the melanoma differentiation-associated protein 5 (MDA5)-mediated-IFN pathway by suppressing the MDA5 expression, and knockout DOT1L rescued the expression of MDA5 and signal transducer and activator of transcription 1 (STAT1), both of which tightly control the antiviral innate immunity. Collectively, it can be deduced from the current data that blocking DOT1L activity or deletion of DOT1L can lead to ALV-J replication inhibition and restoration of the virally suppressed host innate immunity. Thus, we suggest that DOT1L might be a potential drug target for modulating host innate immune responses to combat ALV-J infection.