Paragonimiasis misdiagnosed as liver abscess: A case report.

BACKGROUND: Paragonimiasis is a typical food-borne zoonotic disease. Hosts acquire Paragonimus infection through the ingestion of raw or undercooked crayfish and crab. The clinical manifestations of the disease are varied, and it is often misdiagnosed or missed. The diagnosis of paragonimiasis should be considered comprehensively. Praziquantel is the first choice for treatment, and albendazole can be used in combination with repeated courses in severe cases. CASE SUMMARY: We report a case of liver paragonimiasis that was misdiagnosed as an abscess. The patient presented with fatigue and poor appetite for 2 months, and was diagnosed with liver abscess in the local hospital. After 6 months, the patient visited our hospital because of recurrent abdominal pain and was diagnosed with liver paragonimiasis based on epidemiological history, clinical presentations, and laboratory findings. He was treated with praziquantel (25 mg/kg) three times a day for 3 days; however, the symptoms still presented after treatment. He was treated with oral praziquantel and albendazole for one further course. Follow-up suggested that the treatment was effective and the symptoms improved. CONCLUSION: The combination of albendazole and praziquantel may improve the therapeutic efficacy of paragonimiasis.

[Retracted] Germacrone cooperates with dexmedetomidine to alleviate high­fat diet­induced type 2 diabetes mellitus via upregulating AMPKα1 expression.

[This retracts the article DOI: 10.3892/etm.2019.7990.].

A bispecific anti-PD-1 and PD-L1 antibody induces PD-1 cleavage and provides enhanced anti-tumor activity.

Combinatorial strategies, such as targeting different immune checkpoint receptors, hold promise to increase the breadth and duration of the response to cancer therapy. Here we describe the preclinical evaluation of CTX-8371, a protein construct which combines PD-1 and PD-L1 targeting in one bispecific, tetravalent antibody. CTX-8371 matched or surpassed the activity of anti-PD-1 and PD-L1 benchmark antibodies in several in vitro T cell activation assays and outperformed clinically approved benchmarks in the subcutaneous MC38 colon and the B16F10 lung metastasis mouse tumor models. Investigation into the mechanism of action revealed that CTX-8371 co-engagement of PD-1 and PD-L1 induced the proteolytic cleavage and loss of cell surface PD-1, which is a novel and non-redundant mechanism that adds to the PD-1/PD-L1 signaling axis blockade. The combination of CTX-8371 and an agonistic anti-CD137 antibody further increased the anti-tumor efficacy with long-lasting curative therapeutic effect. In summary, CTX-8371 is a novel checkpoint inhibitor that might provide greater clinical benefit compared to current anti-PD-1 and PD-L1 antibodies, especially when combined with agents with orthogonal mechanisms of action, such as agonistic anti-CD137 antibodies.

Hollow cubic ternary PdCuB nanocage electrocatalysts with greatly enhanced catalytic performance for formic acid oxidation.

The prepared PdCuB Ngs/C catalysts exhibited outstanding catalytic activity and stability in the formic acid oxidation reaction (FAOR). The improvement in electrocatalytic performance is due to the introduction of Cu and B atoms and the hollow nanocage structure, which changes the electronic structures of Pd, increases the reactive sites, and accelerates the reaction mass transfer rates.

Aromatic pentaamide macrocycles bind anions with high affinity for transport across biomembranes.

The convergent positioning of functional groups in biomacromolecules leads to good binding, catalytic and transport capabilities. Synthetic frameworks capable of convergently locking functional groups with minimized conformational uncertainty-leading to similar properties-are highly desirable but rare. Here we report C5-symmetric aromatic pentaamide macrocycles synthesized in one pot from the corresponding monomers. Their crystal structures reveal a star-shaped, fully constrained backbone that causes ten alternating NH/CH hydrogen-bond donors and five large amide dipoles to orient towards the centre of the macrocycle. With a highly electropositive cavity in a high-energy unbound state, the macrocycles bind anions in a 1:1 stoichiometry in solution, with high affinity for halides and very high affinity for oxoanions. We demonstrate that such macrocycles are able to transport anions across lipid bilayers with a high chloride selectivity and restore the depleted airway surface liquid of cystic fibrosis airway cell cultures.

An Interesting Case of Methicillin-Resistant Staphylococcus aureus Prostate Abscess in an Immunocompetent Patient.

Prostate abscess is a rare complication of prostatitis, typically observed in patients with conditions such as immunodeficiency, diabetes, urinary tract abnormalities, and chronic indwelling catheters. Gram-negative bacteria such as Enterobacteriaceae are the most commonly detected organisms in prostate abscesses. Methicillin-resistant Staphylococcus aureus (MRSA) infections are rarely reported. The unique aspect of our case involves MRSA bacteria, further complicated by an MRSA prostate abscess, in a 61-year-old immunocompetent male. The patient, with a past medical history of hypertension and diabetes, presented to the emergency department complaining of nausea and vomiting for four days, with an associated subjective fever and right-sided abdominal pain. A computed tomography (CT) scan of the abdomen/pelvis with contrast showed a prostatic abscess, with abscess/phlegmon extending bilaterally into the seminal vesicles. Urine and blood cultures were positive for MRSA. Initially, Piperacillin/Tazobactam and Vancomycin were initiated. Subsequently, the treatment was switched to Daptomycin. The patient also underwent cystoscopy with urethral dilation, transurethral prostate resection, and unroofing. Although MRSA is not a typical causative agent of prostatitis, it should be considered in the differential diagnosis, especially when clinical improvement cannot be achieved with standard empirical treatment. Timely identification and appropriate treatment (such as drainage and antibiotics) are crucial for both patient survival and the prevention of complications.

How to understand high global food price? Using SHAP to interpret machine learning algorithm.

The global food prices have surged to historical highs, and there is no consensus on the reasons behind this round of price increases in academia. Based on theoretical analysis, this study uses monthly data from January 2000 to May 2022 and machine learning models to examine the root causes of that period's global food price surge and global food security situation. The results show that: Firstly, the increase in the supply of US dollars and the rise in oil prices during pandemic are the two most important variables affecting food prices. The unlimited quantitative easing monetary policy of the US dollar is the primary factor driving the global food price surge, and the alternating impact of oil prices and excessive US dollar liquidity are key features of the surge. Secondly, in the context of the global food shortage, the impact of food production reduction and demand growth expectations on food prices will further increase. Thirdly, attention should be paid to potential agricultural import supply chain risks arising from international uncertainty factors such as the ongoing Russia-Ukraine conflict. The Russian-Ukrainian conflict has profoundly impacted the global agricultural supply chain, and crude oil and fertilizers have gradually become the main driving force behind the rise in food prices.

Antifungal Mechanism of Phenazine-1-Carboxylic Acid against Pestalotiopsis kenyana.

Pestalotiopsis sp. is an important class of plant pathogenic fungi that can infect a variety of crops. We have proved the pathogenicity of P. kenyana on bayberry leaves and caused bayberry blight. Phenazine-1-carboxylic acid (PCA) has the characteristics of high efficiency, low toxicity, and environmental friendliness, which can prevent fungal diseases on a variety of crops. In this study, the effect of PCA on the morphological, physiological, and molecular characteristics of P. kenyana has been investigated, and the potential antifungal mechanism of PCA against P. kenyana was also explored. We applied PCA on P. kenyana in vitro and in vivo to determine its inhibitory effect on PCA. It was found that PCA was highly efficient against P. kenyana, with EC50 around 2.32 µg/mL, and the in vivo effect was 57% at 14 µg/mL. The mechanism of PCA was preliminarily explored by transcriptomics technology. The results showed that after the treatment of PCA, 3613 differential genes were found, focusing on redox processes and various metabolic pathways. In addition, it can also cause mycelial development malformation, damage cell membranes, reduce mitochondrial membrane potential, and increase ROS levels. This result expanded the potential agricultural application of PCA and revealed the possible mechanism against P. kenyana.

Generalizability and Diagnostic Performance of AI Models for Thyroid US.

Background Artificial intelligence (AI) models have improved US assessment of thyroid nodules; however, the lack of generalizability limits the application of these models. Purpose To develop AI models for segmentation and classification of thyroid nodules in US using diverse data sets from nationwide hospitals and multiple vendors, and to measure the impact of the AI models on diagnostic performance. Materials and Methods This retrospective study included consecutive patients with pathologically confirmed thyroid nodules who underwent US using equipment from 12 vendors at 208 hospitals across China from November 2017 to January 2019. The detection, segmentation, and classification models were developed based on the subset or complete set of images. Model performance was evaluated by precision and recall, Dice coefficient, and area under the receiver operating characteristic curve (AUC) analyses. Three scenarios (diagnosis without AI assistance, with freestyle AI assistance, and with rule-based AI assistance) were compared with three senior and three junior radiologists to optimize incorporation of AI into clinical practice. Results A total of 10 023 patients (median age, 46 years [IQR 37-55 years]; 7669 female) were included. The detection, segmentation, and classification models had an average precision, Dice coefficient, and AUC of 0.98 (95% CI: 0.96, 0.99), 0.86 (95% CI: 0.86, 0.87), and 0.90 (95% CI: 0.88, 0.92), respectively. The segmentation model trained on the nationwide data and classification model trained on the mixed vendor data exhibited the best performance, with a Dice coefficient of 0.91 (95% CI: 0.90, 0.91) and AUC of 0.98 (95% CI: 0.97, 1.00), respectively. The AI model outperformed all senior and junior radiologists (P < .05 for all comparisons), and the diagnostic accuracies of all radiologists were improved (P < .05 for all comparisons) with rule-based AI assistance. Conclusion Thyroid US AI models developed from diverse data sets had high diagnostic performance among the Chinese population. Rule-based AI assistance improved the performance of radiologists in thyroid cancer diagnosis. © RSNA, 2023 Supplemental material is available for this article.

High-affinity single and double helical pseudofoldaxanes with cationic guests.

Two aromatic oligoamides, the 8-residue H8 and 16-residue H16, that adopt stable, cavity-containing helical conformations were examined for their complexation of a rodlike dicationic guest, octyl viologen (OV2+) and para-bis(trimethylammonium)benzene (TB2+). Studies based on 1D and 2D 1H NMR, isothermal titration calorimetry (ITC), and X-ray crystallography demonstrated that H8 and H16 wraps around two OV2+ ions as a double helix and a single helix, respectively, resulting in 2 : 2 and 1 : 2 complexes. Compared to H8, the longer H16 binds the OV2+ ions with much higher binding affinity and with extraordinary negative cooperativity. In contrast to its 1 : 2 binding with OV2+, the binding of helix H16 with the bulkier guest TB2+ shows a 1 : 1 ratio. Host H16 also selectively binds OV2+ in the presence of TB2+. This novel host-guest system features pairwise placement of the otherwise strongly repulsive OV2+ ions in the same cavity, strong negative cooperativity, and mutual adaptability of hosts and guests. The resultant complexes are highly stable [2]-, [3]-, and [4]pseudo-foldaxanes with few known precedents.

Covalently Linked Hexakis(m-Phenylene Ethynylene) Macrocycles as Molecular Nanotubes.

The construction of nanotubular structures with non-deformable inner pores is of both fundamental and practical significance. Herein we report a strategy for creating molecular nanotubes with defined lengths. Macrocyclic (MC) units based on shape-persistent hexakis(m-phenylene ethynylene) (m-PE) macrocycle MC-1, which are known to stack into hydrogen-bonded tubular assemblies, are tethered by oligo(ß-alanine) linkers to give tubular stacks MC-2 and MC-4 that have two and four MC units, respectively. The covalently linked MC units in MC-2 and MC-4 undergo face-to-face stacking through intramolecular non-covalent interactions that further results in the helical stacks of these compounds. Oligomer MC-4 can form potassium and proton channels across lipid bilayers, with the channels being open continuously for over 60 seconds, which is among the longest open durations for synthetic ion channels and indicates that the thermodynamic stability of the self-assembling channels can be drastically enhanced by reducing the number of molecular components involved. This study demonstrates that covalently tethering shape-persistent macrocyclic units is a feasible and reliable approach for building molecular nanotubes that otherwise are difficult to create de novo. The extraordinarily long lifetimes of the ion channels formed by MC-2 and MC-4 suggest the likelihood of constructing the next-generation synthetic ion channels with unprecedented stability.

Diversity of endosymbionts in camellia spiny whitefly, Aleurocanthus camelliae (Hemiptera: Aleyrodidae), estimated by 16S rRNA analysis and their biological implications.

Camellia spiny whitefly, Aleurocanthus camelliae (Hemiptera: Aleyrodidae), is a major pest in tea, which poses a serious threat to tea production. Similar to many insects, various bacterial symbioses inside A. camelliae may participate in the reproduction, metabolism, and detoxification of the host. However, few reports included research on the microbial composition and influence on A. camelliae growth. We first applied high-throughput sequencing of the V4 region in the 16S rRNA of symbiotic bacteria to study its component and effect on the biological trait of A. camelliae by comparing it with the antibiotic treatment group. The population parameters, survival rate, and fecundity rate of A. camelliae were also analyzed using the age-stage two-sex life table. Our results demonstrated that phylum Proteobacteria (higher than 96.15%) dominated the whole life cycle of A. camelliae. It unveiled the presence of Candidatus Portiera (primary endosymbiont) (67.15-73.33%), Arsenophonus (5.58-22.89%), Wolbachia (4.53-11.58%), Rickettsia (0.75-2.59%), and Pseudomonas (0.99-1.88%) genus. Antibiotic treatment caused a significant decrease in the endosymbiont, which negatively affected the host's biological properties and life process. For example, 1.5% rifampicin treatment caused a longer preadult stage in the offspring generation (55.92 d) compared to the control (49.75d) and a lower survival rate (0.36) than the control (0.60). The decreased intrinsic rate of increase (r), net reproductive rate (R 0), and prolonged mean generation time (T) were signs of all disadvantageous effects associated with symbiotic reduction. Our findings confirmed the composition and richness of symbiotic bacteria in larva and adult of A. camelliae by an Illumina NovaSeq 6000 analysis and their influence on the development of the host by demographic research. Together, the results suggested that symbiotic bacteria play an important role in manipulating the biological development of their hosts, which might help us for developing new pest control agents and technologies for better management of A. camelliae.

Impact of nanopesticide CuO-NPs and nanofertilizer CeO2-NPs on wheat Triticum aestivum under global warming scenarios.

Concurrent effect of nanomaterials (NMs) and warming on plant performance remains largely unexplored. In this study, the effects of nanopesticide CuO and nanofertilizer CeO2 on wheat (Triticum aestivum) under optimal (22 °C) and suboptimal (30 °C) temperatures were evaluated. CuO-NPs exerted a stronger negative effect on plant root systems than CeO2-NPs at tested exposure levels. The toxicity of both NMs could be attributed to altered nutrient uptake, induced membrane damage, and raised disturbance of antioxidative related biological pathways. Warming significantly inhibited root growth, which was mainly linked to the disturbance of energy metabolism relevant biological pathways. The toxicity of NMs was enhanced upon warming, with a stronger inhibition of root growth and Fe and Mn uptake. Increasing temperature increased the accumulation of Ce upon CeO2-NP exposure, while the accumulation of Cu was not affected. The relative contribution of NMs and warming to their combined effects was evaluated by comparing disturbed biological pathways under single and multiple stressors. CuO-NPs was the dominant factor inducing toxic effects, while both CeO2-NPs and warming contributed to the mixed effect. Our study revealed the importance of carefully considering global warming as a factor in risk assessment of agricultural applications of NMs.

Interactions of molybdenum disulfide nanosheets with wheat plants under changing environments: More than meets the eye?

Molybdenum disulfide (MoS2) nanosheets are being increasingly employed in various applications. It is therefore imperative to assess their potential environmental implications in a changing world, particularly in the context of global warming. Here, we assessed the effects of MoS2 nanosheets on wheat Triticum aestivum L. under today's typical climatic conditions (22 °C) and future climatic conditions (30 °C), respectively. The results showed that MoS2 nanosheets (10 and 100 Mo mg/L) did not significantly affect wheat plant growth, root morphological traits, and chlorophyll fluorescence, regardless of dose and temperature. However, the metabolic processes were significantly altered in T. aestivum upon exposure to individual MoS2 nanosheets and to a combination of MoS2 nanosheets and future global warming. As a non-specific protective strategy, the wheat plants that were under stress conditions maintained the stability of cell membranes and thus relieved cell injury by accumulating more glycerophospholipids. Warming additionally influenced the nitrogen and carbon pool reallocation in wheat root. MoS2 nanosheets mainly depleted a range of antioxidant metabolites involved in phenylpropanoid biosynthesis and taurine and hypotaurine metabolism, while warming activated vitamin B6 cofactors related to vitamin B6 metabolism. Metabolites involved in glutathione metabolism were uniquely upregulated while most metabolites associated with nucleotide metabolisms were uniquely downregulated in combination-treated wheat. Overall, wheat plants regulated a wide range of growth-related processes, including carbohydrate, amino acids, lipid, vitamins, and nucleotide metabolism, to maintain optimal metabolite pool sizes and eventually global metabolic homeostasis upon different stress conditions. Our findings provide novel insights into MoS2 nanosheets-mediated crop responses under global warming.

Anti-4-1BB immunotherapy enhances systemic immune effects of radiotherapy to induce B and T cell-dependent anti-tumor immune activation and improve tumor control at unirradiated sites.

Radiation therapy (RT) can prime and boost systemic anti-tumor effects via STING activation, resulting in enhanced tumor antigen presentation and antigen recognition by T cells. It is increasingly recognized that optimal anti-tumor immune responses benefit from coordinated cellular (T cell) and humoral (B cell) responses. However, the nature and functional relevance of the RT-induced immune response are controversial, beyond STING signaling, and agonistic interventions are lacking. Here, we show that B and CD4+ T cell accumulation at tumor beds in response to RT precedes the arrival of CD8+ T cells, and both cell types are absolutely required for abrogated tumor growth in non-irradiated tumors. Further, RT induces increased expression of 4-1BB (CD137) in both T and B cells; both in preclinical models and in a cohort of patients with small cell lung cancer treated with thoracic RT. Accordingly, the combination of RT and anti-41BB therapy leads to increased immune cell infiltration in the tumor microenvironment and significant abscopal effects. Thus, 4-1BB therapy enhances radiation-induced tumor-specific immune responses via coordinated B and T cell responses, thereby preventing malignant progression at unirradiated tumor sites. These findings provide a rationale for combining RT and 4-1bb therapy in future clinical trials.

Increasing Temperatures Potentiate the Damage of Rare Earth Element Yttrium to the Crop Plant Triticum aestivum L.

Given that increasing temperature may aggravate the toxicity of pollutants, it is a daunting challenge to evaluate the realistic risks of rare earth elements (REEs) under global warming. Here, we studied how elevated temperatures (27 and 32 °C) impact the effect of yttrium (Y) on wheat plants (Triticum aestivum L.) at concentrations not causing effects (0, 0.5, and 1 µM) at the control temperature (22 °C) in a hydroponic system. After 14 days of exposure, significant inhibition (p < 0.05, 29.5%) of root elongation was observed only at 1 µM of Y at 32 °C. Exposure to Y at 27 °C showed no visible effects on root length, but induced significant (p < 0.05) metabolic disorders of a range of carbohydrates and amino acids related to galactose, phenylalanine, and glutamate metabolisms. Such cases were even shifted to substantial perturbation of the nucleotide pool reallocation involved in the disruption of purine and pyrimidine metabolism at 32 °C. These observations were regulated by sets of genes involved in these perturbed pathways. Using weighted gene co-expression network analysis, the disorder of nucleotide metabolism was shown to be responsible for the aggravated Y phytotoxicity at the extreme high temperature. Although the temperature fluctuation considered seems to be in an extreme range, unexpected implications driven by high temperature cannot be neglected. Our findings thus reduce the gaps of knowledge in REE toxicity to plants under future climate warming scenarios and highlight the importance of incorporating environmental temperature into the framework of the risk assessment of REEs.

Ultra-Tight Host-Guest Binding with Exceptionally Strong Positive Cooperativity.

Cooperativity plays a critical role in self-assembly and molecular recognition. A rigid aromatic oligoamide macrocycle with a cyclodirectional backbone binds with DABCO-based cationic guests in a 2 : 1 ratio in high affinities (Ktotal ≈1013  M-2 ) in the highly polar DMF. The host-guest binding also exhibits exceptionally strong positive cooperativity quantified by interaction factors α that are among the largest for synthetic host-guest systems. The unusually strong positive cooperativity, revealed by isothermal titration calorimetry (ITC) and fully corroborated by mass spectrometry, NMR and computational studies, is driven by guest-induced stacking of the macrocycles and stabilization from the alkyl end chains of the guests, interactions that appear upon binding the second macrocycle. With its tight binding driven by extraordinary positive cooperativity, this host-guest system provides a tunable platform for studying molecular interactions and for constructing stable supramolecular assemblies.

Subcellular localization and compartment-specific toxicokinetics of cadmium, arsenic, and zinc in brandling worm Eisenia fetida.

Awareness of toxicokinetics at the subcellular level is crucial to deciphering the underlying intoxication processes of metal(loid)s, although this information is often lacking. Here, the toxicokinetics of two non-essential metal(loid)s (Cd and As) and one essential metal (Zn) in both the whole body and subcellular fractions of earthworm (Eisenia fetida) were assessed. Earthworms were exposed to natural soils originating from a gradient of metal(loid) pollution for 14 days followed by a 14-day elimination phase in clean soil. Clearly distinct toxicokinetic patterns were found in the earthworms according to the metal(loid) considered. An obvious concentration-dependent increase was observed in earthworms or subcellular compartments where no equilibrium was reached (with slow or no elimination) for Cd and As throughout the experiment. As for Zn, the earthworms were able to retain a steady-state concentration of Zn in its body or each fraction without a clear intake behavior via the dynamic trade-off between uptake and elimination at different pollution levels. These differences in toxicokinetics at the subcellular level supported the observed differences in bioaccumulation patterns and were indicative of the strategy by which non-essential and essential elements are handled by earthworms. Notably, the concentration of Cd and As in subcellular compartments showed the same pattern as for Zn in the order of cellular cytosol > cellular debris > metal-rich granules, which might be associated with the binding of non-essential/essential elements with metallothionein enriched in the cytosol. Our findings enhance the understanding of the underlying mechanisms for metal(loid) accumulation kinetics in earthworms from the perspective of subcellular partitioning, and will be beneficial for accurate risk assessment of Cd, As, and Zn.

Cavity-containing aromatic oligoamide foldamers and macrocycles: progress and future perspectives.

As a major class of foldamers, aromatic oligoamide foldamers have attracted intense interest. The rigidity of aromatic residues and amide linkages allows the development of foldamers with readily predictable, stable conformations. Aromatic oligoamide foldamers having backbones fully constrained by intramolecular hydrogen bonds have attracted wide attention. Depending on their lengths, such foldamers adopt crescent or helical conformations with highly negative inner cavities. Cyclizing the backbone of the aromatic oligoamides affords the corresponding macrocycles which are characterised by persistent shapes and non-deformable inner cavities. With their defined, inner cavities, such aromatic oligoamide foldamers and macrocycles have served as hosts for cationic and polar guests, and as transmembrane channels for transporting ions and molecules. Recent synthetic progress resulted in the construction of multi-turn hollow helices that offer three-dimensional inner pores with adjustable depth. Reducing the number of backbone-constraining hydrogen bonds leads to oligoamides which, with their partially constrained backbones, undergo either solvent- or guest-dependent folding. One class of such aromatic olgioamide foldamders, which offer multiple backbone amide NH groups as hydrogen-bond donors, are designed to bind anions with adjustable affinities.