New insights into the evolution and local adaptation of the genus Castanea in east Asia.

Chestnut plants (Castanea) are important nut fruit trees worldwide. However, little is known regarding the genetic relationship and evolutionary history of different species within the genus. How modern chestnut plants have developed local adaptation to various climates remains a mystery. The genomic data showed that Castanea henryi first diverged in the Oligocene ~31.56 million years ago, followed by Castanea mollissima, and the divergence between Castanea seguinii and Castanea crenata occurred in the mid-Miocene. Over the last 5 million years, the population of chestnut plants has continued to decline. A combination of selective sweep and environmental association studies was applied to investigate the genomic basis of chestnut adaptation to different climates. Twenty-two candidate genes were associated with temperature and precipitation. We also revealed the molecular mechanism by which CmTOE1 interacts with CmZFP8 and CmGIS3 to promote the formation of non-glandular trichomes for adaptation to low temperature and high altitudes. We found a significant expansion of CER1 genes in Chinese chestnut (C. mollissima) and verified the CmERF48 regulation of CmCER1.6 adaptation to drought environments. These results shed light on the East Asian chestnut plants as a monophyletic group that had completed interspecific differentiation in the Miocene, and provided candidate genes for future studies on adaptation to climate change in nut trees.

The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy.

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.

Rapid, in-situ evaluation of sunflower seed freshness and vigor using Raman microspectroscopy scanning of carotenoids.

An ultra-rapid, in-situ Raman microscopy strategy was developed for judging both seed freshness and seed vigor based on relative quantification of carotenoids content during sunflower seed germination. The carotenoids content was determined using the ratio of the Raman peak intensities at 1525 and 1268 cm-1 (I1525/1268). When different samples (harvest times and storage conditions) were soaked in water for 0-24 h, the carotenoids content in the embryonic axes gradually increased, with the carotenoids higher in fresher seeds. Using this method, freshly harvested sunflower seeds (2022) were successfully discriminated from seeds harvested over three previous years (2019-2021) and from seeds subjected to accelerated aging at 45 °C or 60 °C for 2-8 days, the samples were correctly differentiated >90%. In addition, a linear correlation between I1525/1268 ratio and seed germination was found (R2 > 0.95). This proposed method can serve as an ultra-rapid strategy for determination of sunflower seed quality.

A novel "mix-response" biosensor for colorimetric and photothermal dual-mode detection of sulfide ions in food based on silver-doping Prussian blue nanoparticle.

Effective identification of sulfur ions (S2-) in foodstuff is crucial for food safety and human health, but it remains challenging. Traditional single-mode colorimetric sensing methods are simple and sensitive, but are prone to interference from colored substances which can lead to false positives or negatives results. Herein, we develop a novel "mix-response" biosensor for colorimetric and photothermal dual-mode detection of S2- with good simplicity, sensitivity and portability. In this biosensor, silver-doping Prussian blue nanoparticle (SPB NPs) was used as signal output component, which not only exhibits blue color characteristics, but also has photothermal conversion properties activated by near-infrared (NIR) laser. Upon increasing the S2- concentration, the prepared SPB NPs undergo etching, leading to the formation of new silver sulfide precipitation (Ag2S), along with different colorimetric and photothermal response signals. For the portable visualization of S2-, the color information was recorded by a smartphone in combination with RGB (red channel) analysis and the evolution of the photothermal signal was documented by a thermal imager. The introduction of smartphone and handheld thermal imager in this "mix-response" biosensor makes it suitable for on-site quantitative detection of S2- without sophisticated instrument. Moreover, the development of this "mix-response" biosensor does not need the use of recognition probes (e.g. aptamers and reaction intermediates), thereby simplifying the construct procedures of sensing strategies and improving the economic efficiency of detection. More importantly, the photothermal response signals can overcome the interference of colored substances in foods, thereby reducing the false positives or negatives of the detection results.

Rational construction of a high-quality and high-efficiency biosynthetic system and fermentation optimization for A82846B based on combinatorial strategies in Amycolatopsis orientalis.

BACKGROUND: Oritavancin is a new generation of semi-synthetic glycopeptide antibiotics against Gram-positive bacteria, which served as the first and only antibiotic with a single-dose therapeutic regimen to treat ABSSSI. A naturally occurring glycopeptide A82846B is the direct precursor of oritavancin. However, its application has been hampered by low yields and homologous impurities. This study established a multi-step combinatorial strategy to rationally construct a high-quality and high-efficiency biosynthesis system for A82846B and systematically optimize its fermentation process to break through the bottleneck of microbial fermentation production. RESULTS: Firstly, based on the genome sequencing and analysis, we deleted putative competitive pathways and constructed a better A82846B-producing strain with a cleaner metabolic background, increasing A82846B production from 92 to 174 mg/L. Subsequently, the PhiC31 integrase system was introduced based on the CRISPR-Cas12a system. Then, the fermentation level of A82846B was improved to 226 mg/L by over-expressing the pathway-specific regulator StrR via the constructed PhiC31 system. Furthermore, overexpressing glycosyl-synthesis gene evaE enhanced the production to 332 mg/L due to the great conversion of the intermediate to target product. Finally, the scale-up production of A82846B reached 725 mg/L in a 15 L fermenter under fermentation optimization, which is the highest reported yield of A82846B without the generation of homologous impurities. CONCLUSION: Under approaches including blocking competitive pathways, inserting site-specific recombination system, overexpressing regulator, overexpressing glycosyl-synthesis gene and optimizing fermentation process, a multi-step combinatorial strategy for the high-level production of A82846B was developed, constructing a high-producing strain AO-6. The combinatorial strategies employed here can be widely applied to improve the fermentation level of other microbial secondary metabolites, providing a reference for constructing an efficient microbial cell factory for high-value natural products.

Transfer learning improves predictions in lignin content of Chinese fir based on Raman spectra.

Lignin in biomass plays significant role in substitution of synthetic polymer and reduction of energy expenditure, and the lignin content was usually determined by wet chemical methods. However, the methods' heavy workload, low efficiency, huge consumption of chemicals and use of toxic reagents render them unsuitable for sustainable development and environmental protection. Chinese fir, a prevalent angiosperm tree, holds immense importance for various industries. Since our previous work found that Raman spectroscopy could accurately predict the lignin content in poplar, we propose that the lignin content of Chinese fir can be estimated by similar strategy. The results suggested that the peak at 2895 cm-1 is the optimal choice of internal standard peak and algorithm of XGBoost demonstrates the highest accuracy among all algorithms. Furthermore, transfer learning was successfully introduced to enhance the accuracy and robustness of the model. Ultimately, we report that a machine learning algorithm, combining transfer learning with XGBoost or LightGBM, offers an accurate, high-efficiency and environmental friendly method for predicting the lignin content of Chinese fir using Raman spectra.

A portable colorimetric sensing platform for rapid and sensitive quantification of dichlorvos pesticide based on Fe-Mn bimetallic oxide nanozyme-participated highly efficient chromogenic catalysis.

BACKGROUND: Dichlorvos (DDVP), as a highly effective insecticide, is widely used in agricultural production. However, DDVP residue in foodstuffs adversely affects human health. Conventional instrumental analysis can provide highly sensitive and accurate detection of DDVP, while the need of bulky and expensive equipment limits their application in resource-poor areas and on-site detection. Therefore, the development of easily portable sensing platforms for convenient, rapid and sensitive quantification of DDVP is very essential for ensuring food safety. RESULT: A portable colorimetric sensing platform for rapid and sensitive quantification of DDVP is developed based on nanozyme-participated highly efficient chromogenic catalysis. The Fe-Mn bimetallic oxide (FeMnOx) nanozyme possesses excellently oxidase-like activity and can efficiently catalyze oxidation of 3, 3', 5, 5'-tetramethylbenzidine (TMB) into a blue oxide with a very low Michaelis constant (Km) of 0.0522 mM. The nanozyme-catalyzed chromogenic reaction can be mediated by DDVP via inhibiting the acetylcholinesterase (AChE) activity. Thus, trace DDVP concentration-dependent color evolution is achieved and DDVP can be sensitively detected by spectrophotometry. Furthermore, a smartphone-integrated 3D-printed miniature lightbox is fabricated as the colorimetric signal acquisition and processing device. Based on the FeMnOx nanozyme and smartphone-integrated lightbox system, the portable colorimetric sensing platform of DDVP is obtained and it has a wide linear range from 1 to 3000 ng mL-1 with a low limit of detection (LOD) of 0.267 ng mL-1 for DDVP quantification. SIGNIFICANCE: This represents a new portable colorimetric sensing platform that can perform detection of DDVP in foodstuffs with simplicity, sensitivity, and low cost. The work not only offers an alternative to rapid and sensitive detection of DDVP, but also provides a new insight for the development of advanced sensors by the combination of nanozyme, 3D-printing and information technologies.

Simulation of ultrafast electron diffraction intensity under coherent acoustic phonons.

Ultrafast electron diffraction has been proven to be a powerful tool for the study of coherent acoustic phonons owing to its high sensitivity to crystal structures. However, this sensitivity leads to complicated behavior of the diffraction intensity, which complicates the analysis process of phonons, especially higher harmonics. Here, we theoretically analyze the effects of photoinduced coherent transverse and longitudinal acoustic phonons on electron diffraction to provide a guide for the exploitation and modulation of coherent phonons. The simulation of the electron diffraction was performed in 30-nm films with different optical penetration depths based on the atomic displacements obtained by solving the wave equation. The simulation results exhibit a complex relationship between the frequencies of the phonons and diffraction signals, which highly depends on the laser penetration depth, sample thickness, and temporal stress distribution. In addition, an intensity decomposition method is proposed to account for the in-phase oscillation and high harmonics caused by inhomogeneous excitation. These results can provide new perspectives and insights for a comprehensive and accurate understanding of the lattice response under coherent phonons.

Daptomycin production enhancement by ARTP mutagenesis and fermentation optimization in Streptomyces roseosporus.

AIMS: We evaluated whether the randomness of mutation breeding can be regulated through a double-reporter system. We hope that by establishing a new precursor feeding strategy, the production capacity of industrial microorganisms after pilot scale-up can be further improved. METHODS AND RESULTS: In this study, the industrial strain Streptomyces roseosporus L2796 was used as the starter strain for daptomycin production, and a double-reporter system with the kanamycin resistance gene Neo and the chromogenic gene gusA was constructed to screen for high-yield strain L2201 through atmospheric and room temperature plasma (ARTP). Furthermore, the composition of the culture medium and the parameters of precursor replenishment were optimized, resulting in a significant enhancement of the daptomycin yield of the mutant strain L2201(752.67 mg/l). CONCLUSIONS: This study successfully screened a high-yield strain of daptomycin through a double-reporter system combined with ARTP mutation. The expression level of two reporter genes can evaluate the strength of dptEp promoter, which can stimulate the expression level of dptE in the biosynthesis of daptomycin, thus producing more daptomycin. The developed multi-stage feeding rate strategy provides a novel way to increase daptomycin in industrial fermentation.

Humanoid Intelligent Display Platform for Audiovisual Interaction and Sound Identification.

This study proposes a rational strategy for the design, fabrication and system integration of the humanoid intelligent display platform (HIDP) to meet the requirements of highly humanized mechanical properties and intelligence for human-machine interfaces. The platform's sandwich structure comprises a middle light-emitting layer and surface electrodes, which consists of silicon elastomer embedded with phosphor and silk fibroin ionoelastomer, respectively. Both materials are highly stretchable and resilient, endowing the HIDP with skin-like mechanical properties and applicability in various extreme environments and complex mechanical stimulations. Furthermore, by establishing the numerical correlation between the amplitude change of animal sounds and the brightness variation, the HIDP realizes audiovisual interaction and successful identification of animal species with the aid of Internet of Things (IoT) and machine learning techniques. The accuracy of species identification reaches about 100% for 200 rounds of random testing. Additionally, the HIDP can recognize animal species and their corresponding frequencies by analyzing sound characteristics, displaying real-time results with an accuracy of approximately 99% and 93%, respectively. In sum, this study offers a rational route to designing intelligent display devices for audiovisual interaction, which can expedite the application of smart display devices in human-machine interaction, soft robotics, wearable sound-vision system and medical devices for hearing-impaired patients.

First Report of Apiospora arundinis Causing Wet Root Rot of Pseudostellaria heterophylla in China.

Pseudostellaria heterophylla is one of the traditional medicines in China. From 2020 to 2022, postharvest wet root rot disease was observed with an incidence of 2~5% on the tuberous roots of the harvested P. heterophylla in Zherong county, Fujian province, China, which usually occurs under damp and unventilated conditions. The symptoms of the disease were as follows: white mycelia grew on the surface of tuberous root initially and gradually wrapped around the roots, the internal root tissue turned yellow and became wet decay finally. To identify the causal agent, a total of 20 samples with symptomatic tuberous roots were collected. Small pieces (3 mm2) were treated by surface disinfection with 75% ethanol and 1% NaOCl, then rinsed 3 times with sterile water. These treated pieces were transferred onto potato dextrose agar (PDA) and incubated at 25°C in the dark for 7 d. Ten pure cultures were obtained using single-spore isolation method. The fungus colonies initially produced white aerial mycelium, subsequently exhibited yellow pigmentation. Mycelia were consisted of smooth, hyaline, branched, and septate hyphae. The conidia were solitary or clustered, brown or dark brown, smooth, ellipsoidal to spherical, 6.66 (5.50-7.81)×5.65 (4.17-7.22) µm (n=50) in size. The conidiophores were hyaline or pale brown and produced conidiogenous cells, which were pale brown, smooth, ampulliform, and 10.14 (8.82-15.30) um long (n=50). Based on these morphological characteristics, the fungus was identified as the genus Apiospora (Arthrinium). The rDNA-ITS region and partial ß-tubulin gene (BenA) were amplified using the primers ITS1/ITS4 (White et al. 1990) and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. The sequences of isolates FJAT-32563 and FJAT-32564 were deposited in GenBank (ITS, OM920984 and OM920985; BenA, OM953823 and OM953824). All sequences had more than 99% similarity with those of A. arundinis strain CBS:106.12 (ITS, KF144883; BenA, KF144973). In the multilocus phylogenetic analysis (ITS + BenA), the two isolates clustered together with other strains of A. arundinis with 100% bootstrap support. The isolates were therefore identified as A. arundinis based on both morphological and molecular characteristics. To confirm the pathogenicity, fresh tuberous roots were selected and surface disinfected, then the roots were immersed with a quarter length in the conidial suspension (106/mL) for 30 min, whereas the control roots were immersed with sterile water (n=30). They were placed in petri dish with wet filter paper at 25±2℃, maintaining 80% relative humidity in the dark. The white aerial mycelium appeared at 5 days after inoculation, and wet root rot decaying occurred after inoculation for 21 days. The symptoms were similar to those described above, whereas the control roots were asymptomatic. The same fungus was re-isolated from the infected roots, showing similar morphological characteristics and molecular traits. Koch's postulates were completed and the pathogenicity test for the isolates has been repeated thrice. Previously, A. arundinis was reported to infect peach and sugarcane (Ji et al. 2020; Liao et al. 2022). To our knowledge, this is the first report of A. arundinis causing wet root rot of P. heterophylla in China. The disease would be a potentially new threat to this medicinal plant.

Mechanochemically assisted morphing of shape shifting polymers.

Morphing in creatures has inspired various synthetic polymer materials that are capable of shape shifting. The morphing of polymers generally relies on stimuli-active (typically heat and light active) units that fix the shape after a mechanical load-based shape programming. Herein, we report a strategy that uses a mechanochemically active 2,2'-bis(2-phenylindan-1,3-dione) (BPID) mechanophore as a switching unit for mechanochemical morphing. The mechanical load on the polymer triggers the dissociation of the BPID moiety into stable 2-phenylindan-1,3-dione (PID) radicals, whose subsequent spontaneous dimerization regenerates BPID and fixes the temporary shapes that can be effectively recovered to the permanent shapes by heating. A greater extent of BPID activation, through a higher BPID content or mechanical load, leads to higher mechanochemical shape fixity. By contrast, a relatively mechanochemically less active hexaarylbiimidazole (HABI) mechanophore shows a lower fixing efficiency when subjected to the same programing conditions. Another control system without a mechanophore shows a low fixing efficiency comparable to the HABI system. Additionally, the introduction of the BPID moiety also manifests remarkable mechanochromic behavior during the shape programing process, offering a visualizable indicator for the pre-evaluation of morphing efficiency. Unlike conventional mechanical mechanisms that simultaneously induce morphing, such as strain-induced plastic deformation or crystallization, our mechanochemical method allows for shape programming after the mechanical treatment. Our concept has potential for the design of mechanochemically programmable and mechanoresponsive shape shifting polymers.

A fluorescent method for bisphenol A detection based on enzymatic oxidation-mediated emission quenching of silicon nanoparticles.

As a common raw material of industrial products, bisphenol A (BPA) is widely used in the production of food contact materials, and there is a high risk of exposure in food. However, BPA is a well-known endocrine disruptor and poses a serious threat to human health. Herein, a fluorescent sensing platform of BPA based on enzymatic oxidation-mediated fluorescence quenching of silicon nanoparticles (SiNPs) is established and used to the detection of BPA in food species. The SiNPs are prepared with a facile one-step synthesis and emit bright green fluorescence. BPA can be oxidized by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) to form a product which can quench the fluorescence of SiNPs through electron transfer. There is a good linear relationship between the fluorescence intensity and BPA concentration in the range of 1-100 µM. Therefore, a fluorometry of BPA is established with a low limit of detection (LOD) of 0.69 µM. This method has been applied to the determination of BPA in mineral drinking water, orange juice, and milk with satisfactory results. The fluorescent sensor of BPA based on SiNPs has favorable application foreground in the field of food safety analysis.

An Unusual Case of Lung Adenocarcinoma Metastasis to the Tricep Muscle: Four Years Disease-Free After Surgical Resection and Radiotherapy.

Lung cancer is one of the leading causes of cancer-related death worldwide. Lung cancer commonly metastasizes to the liver, bone, and brain, but metastasis to skeletal muscles is rare. The development of metastasis in skeletal muscles indicates stage IV disease with a poor prognosis. The most effective treatment strategy is unclear. Palliative radiotherapy is often used to treat skeletal muscle metastases, and patient survival is poor, with an average survival of one year. Here we discuss the case of a 76-year-old female diagnosed with lung adenocarcinoma with metastasis to the trapezius muscle. Initially, she was treated with stereotactic body radiotherapy for stage T1 lung adenocarcinoma. Her follow-up surveillance positron emission tomography (PET) scan in 11 months showed an abnormal focal area of increased activity localizing to the long head of the right triceps muscle. The diagnosis was confirmed with an ultrasound-guided biopsy of the trapezius muscle. Following that, the patient underwent wedge resection of the right middle and upper lobe of the lung and partial right trapezius resection. Afterward, she was given radiation therapy at the tricep resection site. She remained disease-free for four years after excision and radiation therapy.

The effect of FMT and vitamin C on immunity-related genes in antibiotic-induced dysbiosis in mice.

Antibiotics are double-edged swords. Although antibiotics are used to inhibit pathogenic bacteria, they also run the risk of destroying some of the healthy bacteria in our bodies. We examined the effect of penicillin on the organism through a microarray dataset, after which 12 genes related to immuno-inflammatory pathways were selected by reading the literature and validated using neomycin and ampicillin. The expression of genes was measured using qRT-PCR. Several genes were significantly overexpressed in antibiotic-treated mice, including CD74 and SAA2 in intestinal tissues that remained extremely expressed after natural recovery. Moreover, transplantation of fecal microbiota from healthy mice to antibiotic-treated mice was made, where GZMB, CD3G, H2-AA, PSMB9, CD74, and SAA1 were greatly expressed; however, SAA2 was downregulated and normal expression was restored, and in liver tissue, SAA1, SAA2, SAA3 were extremely expressed. After the addition of vitamin C, which has positive effects in several aspects, to the fecal microbiota transplantation, in the intestinal tissues, the genes that were highly expressed after the fecal microbiota transplantation effectively reduced their expression, and the unaffected genes remained normally expressed, but the CD74 gene remained highly expressed. In liver tissues, normally expressed genes were not affected, but the expression of SAA1 was reduced and the expression of SAA3 was increased. In other words, fecal microbiota transplantation did not necessarily bring about a positive effect of gene expression restoration, but the addition of vitamin C effectively reduced the effects of fecal microbiota transplantation and regulated the balance of the immune system.

A Rare Case of Relapsed Sarcoidosis Presenting As Severe Thrombocytopenia Associated With Intracerebral Hemorrhage Due to Bone Marrow Involvement.

Sarcoidosis is a systemic granulomatous disease characterized by the hyperactivation of CD4 T cells, CD8 T cells, and macrophages. Clinical presentations of sarcoidosis are highly variable. Sarcoidosis is unknown in its etiology, but it suggests it may result from exposure to specific environmental agents in genetically susceptible people. Sarcoidosis commonly involves the lungs and lymphoid system. Bone marrow involvement in sarcoidosis is uncommon. Sarcoidosis rarely results in intracerebral hemorrhage due to severe thrombocytopenia secondary to bone marrow involvement. We present the case of a 72-year-old woman who has been in remission from sarcoidosis for 15 years and developed intracerebral hemorrhage secondary to severe thrombocytopenia due to sarcoidosis recurrence in the bone marrow. The patient presented to the emergency department with a generalized, non-blanching petechiae rash and nose and gum bleeding. Her labs showed a platelet count of less than 10.000/mcL, and computed tomography (CT) showed intracerebral hemorrhage. A bone marrow biopsy revealed a small, non-caseating granuloma indicative of a sarcoidosis relapse in the bone marrow.

Identification and Characterization of a New Regulator, TagR, for Environmental Stress Resistance Based on the DNA Methylome of Streptomyces roseosporus.

DNA methylation is a defense that microorganisms use against extreme environmental stress, and improving resistance against environmental stress is essential for industrial actinomycetes. However, research on strain optimization utilizing DNA methylation for breakthroughs is rare. Based on DNA methylome analysis and KEGG pathway assignment in Streptomyces roseosporus, we discovered an environmental stress resistance regulator, TagR. A series of in vivo and in vitro experiments identified TagR as a negative regulator, and it is the first reported regulator of the wall teichoic acid (WTA) ABC transport system. Further study showed that TagR had a positive self-regulatory loop and m4C methylation in the promoter improved its expression. The ΔtagR mutant exhibited better hyperosmotic resistance and higher decanoic acid tolerance than the wild type, which led to a 100% increase in the yield of daptomycin. Moreover, enhancing the expression of the WTA transporter resulted in better osmotic stress resistance in Streptomyces lividans TK24, indicating the potential for wide application of the TagR-WTA transporter regulatory pathway. This research confirmed the feasibility and effectiveness of mining regulators of environmental stress resistance based on the DNA methylome, characterized the mechanism of TagR, and improved the resistance and daptomycin yield of strains. Furthermore, this research provides a new perspective on the optimization of industrial actinomycetes. IMPORTANCE This study established a novel strategy for screening regulators of environmental stress resistance based on the DNA methylome and discovered a new regulator, TagR. The TagR-WTA transporter regulatory pathway improved the resistance and antibiotic yield of strains and has the potential for wide application. Our research provides a new perspective on the optimization and reconstruction of industrial actinomycetes.

Case Report of Painless Obstructive Jaundice: A Rare First Presentation of Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) is a very aggressive type of lung cancer that is of neuroendocrine origin. Because of the high levels of circulating tumor cells, it has a very high rate of metastasis. Obstructive jaundice as the initial manifestation of small cell lung carcinoma is rare. Most of the cases are due to extrahepatic cholestasis by biliary duct obstruction. The biliary duct obstruction may be secondary to metastasis to lymph nodes or pancreatic head metastasis. Obstructive jaundice secondary to intrahepatic cholestasis is even rarer. A 75-year-old male presented to the emergency department (ED) with a complaint of new-onset painless jaundice that his dentist incidentally detected. Examination revealed a mass in the right upper quadrant (RUQ) of the abdomen. Computed tomography (CT) angiography of the abdomen, pancreas, and pelvis shows innumerable hepatic hypodensities highly suspicious for metastatic disease. However, there was no extrahepatic dilatation or pancreatic mass. He was diagnosed with diffuse metastasis of small cell lung carcinoma (SCLC) by needle biopsy of the liver. He developed acute kidney injury and liver damage and thus compromised chemotherapy for SCLC. Later, the patient chose comfort care and passed away the next day. To our knowledge, this is the second reported case of SCLC initially presenting as obstructive jaundice secondary intrahepatic cholestasis by diffuse liver metastases.

Resolvin D1 attenuates depressive-like behavior in LPS-challenged mice by promoting microglial autophagy.

It has been proven that neuroinflammation triggered by microglial activation is the pathogenesis of depression associated with sepsis. An endogenous lipid mediator known as resolvin D1 (RvD1) is known to have anti-inflammatory effects in a sepsis model. However, it remains unknown if the effects of RvD1 on inflammatory responses are regulated by microglial autophagy. The current study investigated the role of RvD1-induced microglial autophagy in neuroinflammation. The findings showed that RvD1 reverses LPS-induced autophagy inhibition in microglia. RvD1 treatment significantly inhibits inflammatory responses by preventing NF-κB nuclear translocation and microglial M1 phenotypic transition. RvD1 exhibits an attenuation of neurotoxicity in both in vivo and in vitro models of sepsis. Following RvD1 injection, depressive-like behaviors in SAE mice were significantly improved. Notably, the aforesaid effects of RvD1 were eliminated by 3-MA, demonstrating that microglial autophagy was modulated. In conclusion, our findings shed new light on the involvement of microglial autophagy in SAE and emphasize the potential benefits of RvD1 as a promising therapeutic agent in the treatment of depression.

Degradation mechanism of AtrA mediated by ClpXP and its application in daptomycin production in Streptomyces roseosporus.

The efficiency of drug biosynthesis depends on different transcriptional regulatory pathways in Streptomyces, and the protein degradation system adds another layer of complexity to the regulatory processes. AtrA, a transcriptional regulator in the A-factor regulatory cascade, stimulates the production of daptomycin by binding to the dptE promoter in Streptomyces roseosporus. Using pull-down assays, bacterial two-hybrid system and knockout verification, we demonstrated that AtrA is a substrate for ClpP protease. Furthermore, we showed that ClpX is necessary for AtrA recognition and subsequent degradation. Bioinformatics analysis, truncating mutation, and overexpression proved that the AAA motifs of AtrA were essential for initial recognition in the degradation process. Finally, overexpression of mutated atrA (AAA-QQQ) in S. roseosporus increased the yield of daptomycin by 225% in shake flask and by 164% in the 15 L bioreactor. Thus, improving the stability of key regulators is an effective method to promote the ability of antibiotic synthesis.