The impact of inhalation injury on fluid resuscitation in major burn patients: a 10-year multicenter retrospective study.

BACKGROUND: It remains unclear whether additional fluid supplementation is necessary during the acute resuscitation period for patients with combined inhalational injury (INHI) under the guidance of the Third Military Medical University (TMMU) protocol. METHODS: A 10-year multicenter, retrospective cohort study, involved patients with burns ≥ 50% total burn surface area (TBSA) was conducted. The effect of INHI, INHI severity, and tracheotomy on the fluid management in burn patients was assessed. Cumulative fluid administration, cumulative urine output, and cumulative fluid retention within 72 h were collected and systematically analyzed. RESULTS: A total of 108 patients were included in the analysis, 85 with concomitant INHI and 23 with thermal burn alone. There was no significant difference in total fluid administration during the 72-h post-burn between the INHI and non-INHI groups. Although no difference in the urine output and fluid retention was shown in the first 24 h, the INHI group had a significantly lower cumulative urine output and a higher cumulative fluid retention in the 48-h and 72-h post-burn (all p < 0.05). In addition, patients with severe INHI exhibited a significantly elevated incidence of complications (Pneumonia, 47.0% vs. 11.8%, p = 0.012), (AKI, 23.5% vs. 2.9%, p = 0.037). For patients with combined INHI, neither the severity of INHI nor the presence of a tracheotomy had any significant influence on fluid management during the acute resuscitation period. CONCLUSIONS: Additional fluid administration may be unnecessary in major burn patients with INHI under the guidance of the TMMU protocol.

First molecular survey of tick-borne protozoan and bacterial pathogens in the questing tick population in Bangladesh.

Questing ticks carry various tick-borne pathogens (TBPs) that are responsible for causing tick-borne diseases (TBDs) in humans and animals around the globe, especially in the tropics and sub-tropics. Information on the distribution of ticks and TBPs in a specific geography is crucial for the formulation of mitigation measures against TBDs. Therefore, this study aimed to survey the TBPs in the questing tick population in Bangladesh. A total of 2748 questing hard ticks were collected from the pastures in Sylhet, Bandarban, Sirajganj, Dhaka, and Mymensingh districts through the flagging method. After morphological identification, the ticks were grouped into 142 pools based on their species, sexes, life stages, and collection sites. The genomic DNA extracted from tick specimens was screened for 14 pathogens, namely Babesia bigemina (AMA-1), Babesia bovis (RAP-1), Babesia naoakii (AMA-1), Babesia ovis (18S rRNA), Theileria luwenshuni (18S rRNA), Theileria annulata (Tams-1), Theileria orientalis (MPSP), Anaplasma marginale (groEL), Anaplasma phagocytophilum (16S rRNA), Anaplasma bovis (16S rRNA), Anaplasma platys (16S rRNA), Ehrlichia spp. (16S rRNA), Rickettsia spp. (gltA), and Borrelia (Bo.) spp. (flagellin B) using genus and species-specific polymerase chain reaction (PCR) assays. The prevalence of the detected pathogens was calculated using the maximum likelihood method (MLE) with 95 % confidence interval (CI). Among 2748 ixodid ticks, 2332 (84.86 %) and 416 (15.14 %) were identified as Haemaphysalis bispinosa and Rhipicephalus microplus, respectively. Haemaphysalis bispinosa was found to carry all the seven detected pathogens, while larvae of R. microplus were found to carry only Bo. theileri. Among the TBPs, the highest detection rate was observed in A. bovis (20/142 pools, 0.81 %, CI: 0.51-1.20), followed by T. orientalis (19/142 pools, 0.72 %, CI: 0.44-1.09), T. luwenshuni (9/142 pools, 0.34 %, CI: 0.16-0.62), B. ovis (4/142 pools, 0.15 %, CI: 0.05 - 0.34) and Bo. theileri (4/142 pools, 0.15 %, CI: 0.05-0.34), Ehrlichia ewingii (3/142 pools, 0.11 %, CI: 0.03-0.29), and Babesia bigemina (1/142, 0.04 %, CI: 0.00 - 0.16). This study reports the existence of T. luwenshuni, E. ewingii, and Bo. theileri in Bangladesh for the first time. The novel findings of this study are the foremost documentation of transovarian transmission of B. bigemina and E. ewingii in H. bispinosa and also provide primary molecular evidence on the presence of E. ewingii and Bo. theileri in H. bispinosa. Therefore, this study may shed light on the circulating TBPs in ticks in the natural environment and thereby advocate awareness among physicians and veterinarians to control and prevent TBDs in Bangladesh.

Analysis on the location of scalp acupuncture lines based on the 2021 version of Standardized Manipulations of Acupuncture and Moxibustion--Part 2： Scalp Acupuncture. / 2021版《针灸技术操作规范（第2部分）：头针》头穴线定位疑析.

In order to better promote the popularization and application of the national standard of Standardized Manipulations of Acupuncture and Moxibustion--Part 2： Scalp Acupuncture (GB/T 21709.2-2021), and to provide reference for the improvement and formulation of the next version, in the present paper, the differences about the position descriptions of two scalp acupuncture lines Dingnie Qianxiexian (anterior oblique line of vertex-temporal, MS6) and Dingpangxian 1 (lateral line 1 of vertex, MS8) between the new (GB/T 21709.2-2021) and old (GB/T 21709.2-2008) versions of the national standards as well as the International Standard Proposal of Scalp Acupuncture Point were compared, and the disputes still existing in the 2021 version were discussed. Although the 2021 version has made relevant amendments in some controversial or non-standard contents in the 2008 version, there are still some inappropriate contents. Firstly, only the relevant revision in the attached figure 3 was mentioned in the preface, without mention of the word revision about MS6 in both English and Chinese, but actually "Chengguang" (BL6) has been changed to "Tongtian" (BL7). Secondly, The attached figure does not match the word description. There is a revision in the attached figure and text at the same time, in which the text description of Qianding (GV21) of the MS6 has not been revised, but the front Shencong (EX-HN1) in the attached figure has been changed to GV21, which is obviously inconsistent with the positioning of the MS6 according to the WHO international standard, and the basis for the revision is not known. These revisions of the 2021 version of national standard on the position of the two scalp acupoint lines in the 2008 version are inconsistent, which may make many colleagues in the acupuncture field confused. Thus, further revision is necessary.

Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumor types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

Synergism of jet milling and deep eutectic solvent pretreatment on grapevine lignin fractionation and enhancing enzymatic hydrolysis.

Herein, we investigated the synergistic effects of jet milling (JM) and deep eutectic solvent (DES) pretreatment on the fractionation of grapevine lignin and the consequent enhancement of enzymatic hydrolysis. Grapevine, a substantial byproduct of the wine industry, was subjected to JM pretreatment to produce finely powdered particles (median diameter D50 = 98.90), which were then further treated with acidic ChCl-LA and alkaline K2CO3-EG DESs. The results revealed that the combined JM + ChCl-LA pretreatment significantly increased the cellulose preservation under optimal conditions (110 °C, 4 h, and 20 % water content), achieving removal rates of 74.18 % xylan and 66.05 % lignin, respectively. The pretreatment temperature and inhibitor production were reduced, resulting in a remarkable threefold increase in glucose yield compared to untreated samples. Moreover, the structural analysis of the pretreated lignin indicated an enrichment of phenolic units, leading to enhanced antioxidant and antibacterial activities, particularly in the JM pretreated samples. These findings underscore the promising potential of the synergistic JM and DES pretreatment in facilitating the efficient utilization of grapevine lignocellulosic biomass for sustainable biorefinery technologies.

Structural and functional characteristics of pectins from three cultivars of apple (Malus pumila Mill.) pomaces.

This study aimed to investigate the chemical composition, structural properties, and biological properties of pectin polysaccharides (AP-FS, AP-QG, and AP-HG) isolated from different varieties of apple pomace. Based on the methylation and nuclear magnetic resonance analyses, the structure of AP-FS was determined to be composed of an α-1,4-linked homogalacturonan backbone that exhibited high levels of O-6 methylation. All pectins exhibit potent inhibitory activity against human colon cancer and human liver cancer cells, along with immunostimulatory effects. Among them, AP-FS exhibited the highest activity level. Finally, we further investigated the underlying mechanism behind the effect of AP-FS on RAW 264.7 cells using proteomics analysis. Our findings revealed that AP-FS triggers RAW 264.7 macrophage activation via NOD-like receptor (NLR), NF-κB, and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, our research contributes to a better understanding of the structure-function relationship among apple pectins, and AP-FS has the potential to be applied to dietary supplements targeting immunomodulation.

Three-dimensional DNA nanomachine biosensor coupled with CRISPR Cas12a cascade amplification for ultrasensitive detection of carcinoembryonic antigen.

The detection of carcinoembryonic antigen (CEA) holds significant importance in the early diagnosis of cancer. However, current methods are hindered by limited accessibility and specificity. This study proposes a rapid and convenient Cas12a-based assay for the direct detection of CEA in clinical serum samples, aiming to address these limitations. The protocol involves a rolling machine operation, followed by a 5-min Cas12a-mediated cleavage process. The assay demonstrates the capability to detect human serum with high anti-interference performance and a detection limit as low as 0.2 ng/mL. The entire testing procedure can be accomplished in 75 min without centrifugation steps, and successfully reduced the limit of detection of traditional DNA walking machine by 50 folds. Overall, the testing procedure can be easily implemented in clinical settings.

Intranasal PAMAM-G3 scavenges cell-free DNA attenuating the allergic airway inflammation.

Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However, the underlying mechanism remains uncertain and available treatments are constrained. Consequently, we aim to explore the role of cell-free DNA (cfDNA) in AAI and assess the potential alleviating effects of cationic polymers (CPs) through cfDNA elimination. Levels of cfDNA were evaluated in AR patients, allergen-stimulated human bronchial epithelium (BEAS-2B cells) and primary human nasal epithelium from both AR and healthy control (HC), and AAI murine model. Polyamidoamine dendrimers-generation 3 (PAMAM-G3), a classic type of cationic polymers, were applied to investigate whether the clearance of cfDNA could ameliorate airway epithelial dysfunction and inhibit AAI. The levels of cfDNA in the plasma and nasal secretion from AR were higher than those from HC (P < 0.05). Additionally, cfDNA levels in the exhaled breath condensate (EBC) were positively correlated with Interleukin (IL)-5 levels in EBC (R = 0.4191, P = 0.0001). Plasma cfDNA levels negatively correlated with the duration of allergen immunotherapy treatment (R = -0.4297, P = 0.006). Allergen stimulated cfDNA secretion in vitro (P < 0.001) and in vivo (P < 0.0001), which could be effectively scavenged with PAMAM-G3. The application of PAMAM-G3 inhibited epithelial barrier dysfunction in vitro and attenuated the development of AAI in vivo. This study elucidates that cfDNA, a promising biomarker for monitoring disease severity, aggravates AAI and the application of intranasal PAMAM-G3 could potentially be a novel therapeutic intervention for AAI. Allergen stimulates the secretion of cell-free DNA (cfDNA) in both human and mouse airway. Intranasal polyamidoamine dendrimers-generation 3 (PAMAM-G3) scavenges cfDNA and alleviates allergic airway inflammation.

Home care practice behavior and its influencing factors of primary care providers: a multicenter cross-sectional study in Sichuan Province, China.

BACKGROUND: Primary care providers play an important role in home health care, and their practice behavior is significant for care quality and patient outcomes. This study aimed to assess the home care practice behavior of Chinese primary care providers and to explore the factors associated with the practice behavior. METHODS: A multicenter cross-sectional design with a convenience sample was used to survey 863 registered primary care providers from 62 primary health care settings in Sichuan Province, China. Descriptive statistics, t-test or ANOVA for one-way analysis, and Pearson's correlation analyses were used to compare the differences and examine the relationships between participants' demographics and experience of home care services and practice behavior. Multiple linear regression models were performed to identify salient variables associated with the practice behavior from among demographic and home care experience. RESULTS: The score of home care practice behavior questionnaire was 97.25 ± 21.05. The average scores for the dimensions of home visit preparation, assessment, medical care behavior and safety practice were 3.70 ± 0.95, 3.76 ± 1.02, 3.66 ± 1.03, and 3.20 ± 0.46, respectively. Home care practice behavior was associated with working years, working experience in general hospitals, work area, home care experience such as client types of home care, service frequency and willingness, explaining 21.5% of the total variance. CONCLUSION: Chinese primary care providers had a medium to high level of home care practice behavior but poor implementation of safety practice. The results may provide clues to increased focus and implementation of safety practice, as well as providing targeted measures based on influencing factors.

A causal analysis of the relationship between exposure to sunlight and colorectal cancer risk: A Mendelian randomization study.

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC.

A novel MAPT variant (E342K) as a cause of familial progressive supranuclear palsy.

Background: MAPT variants are a known cause of frontotemporal dementia and Parkinsonian syndrome, of which progressive supranuclear palsy syndrome (PSP) is a rare manifestation. Objective: To report a novel MAPT variant in a PSP pedigree with autosomal dominant inheritance pattern, and to produce a literature review of PSP patients with MAPT variants. Methods: A comprehensive clinical, genetic, and molecular neuroimaging investigation was conducted on a 61 years-old female proband diagnosed with PSP. We also collected the clinical presentation data and history of the patient's pedigree, and performed further genetic analysis of 4 relatives, from two generations, with and without symptoms. Results: The proband exhibited typical clinical manifestation of PSP. A cranial MRI revealed midbrain atrophy, and an FDG-PET scan suggested hypo-metabolic changes in caudate nucleus, left prefrontal lobe, both temporal poles, and midbrain. 18F-florzolo-tau-PET revealed tau-protein deposits in the thalamus and brainstem bilaterally. A gene test by whole-exome sequencing identified a novel MAPT variant [NM_005910.6, exon 11, c.1024G > A (p.E342K)], and the same variant was also identified in one affected relative and one asymptomatic relative, a probable pre-symptomatic carrier. Conclusion: The PSP pedigree caused by the novel MAPT (E342K) variant, expanded the mutational spectrum of MAPT.

Regorafenib for patients with progression of advanced hepatocellular carcinoma after treatment with atezolizumab plus bevacizumab: a case series.

Background: Immunotherapy has reshaped the systemic treatment of hepatocellular carcinoma (HCC), with atezolizumab plus bevacizumab (TA) regimen and regorafenib being the first-line and second-line treatment options for advanced HCC, respectively. However, the efficacy of using the second-line therapeutic agent regorafenib in patients with HCC that has progressed after TA regimen treatment is unknown, and there is a lack of supporting clinical data. The purpose of this case series was to evaluate the clinical efficacy of the second-line therapeutic agent regorafenib in patients with advanced HCC who progressed after treatment with a first-line TA regimen. Case Description: This case series included five patients with intermediate to advanced HCC treated with regorafenib after progression on a TA regimen. We retrospectively report the clinical data, clinical outcomes, and adverse events of these five patients. According to modified Response Evaluation Criteria in Solid Tumors (mRECIST), one patient achieved partial response (PR), three patients achieved stable disease (SD), and one patient experienced progressive disease (PD); the disease control rate (DCR) reached 80%, and the objective response rate (ORR) reached 20%. Conclusions: In patients with intermediate to advanced HCC who experience disease progression after TA therapy, second-line treatment with regorafenib may be effective in delaying progression and may be associated with better disease control. However, these findings need to be further confirmed in prospective studies with larger cohorts.

Inhibition of histone deacetylase promotes a neuroprotective mechanism in an experimental model of Parkinson's disease.

Introduction: Therapies targeting histone deacetylase (HDAC) have gained wider attention in the treatment of various clinical conditions. However, the use of HDAC inhibitors in pre-clinical trials in the case of Parkinson's disease (PD) is very limited. In the present study, the HDAC inhibitor, entinostat, was tested in animals induced with Parkinson's disease experimentally. Material and methods: Wistar male rats (150 ±10 g) were administered with rotenone (2 mg/kg/day, s.c.) for 21 days to induce PD, while entinostat (20 mg/kg) was given intraperitoneally. Then, the neurological functions, PD markers, and HDACs were analysed in the control and experimental animals. Results: The results demonstrated that rats that received entinostat displayed progressive motor, behavioural, and neurological function with attenuated α-synuclein and improved tyrosine-hydroxylase compared to control cells. Moreover, the induction of PD in rats demonstrated reduced levels of H2S, dopamine, 3, and 4-dihydroxyphenylacetic acid (DOPAC), and increased monoamine oxidase activity in PD rats. However, the rats that received entinostat demonstrated progressive levels of dopa and DOPAC, with attenuated levels of HDAC-2, -4, and -6 mRNA in the PD rats compared to controls. On the other hand, elevated (p < 0.01) levels of PD marker genes such as GDF3 and NMDA2b were reduced, with a significant increase in neuroprotective genes such as VDAC3 and CBX5 in entinostat-supplemented rats. Conclusions: The study results suggest that inhibition of HDAC systematically improves the neurological functions, and hence treatments, emphasizing that HDACI, as the speculated mechanism, will be a promising mode of treatment in PD.

Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma.

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads to significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk and single-cell transcriptomics, and spatial transcriptomics and proteomics. Vertical invasion from AMis to iAM displays an early and monoclonal seeding pattern. The subsequent regional expansion of iAM exhibits two distinct patterns, clonal expansion and subclonal diversification. Notably, molecular subtyping reveals an aggressive iAM subset featured with subclonal diversification, increased epithelial-mesenchymal transition (EMT), and spatial enrichment of APOE+/CD163+ macrophages. In vitro and ex vivo experiments further demonstrate that APOE+CD163+ macrophages promote tumor EMT via IGF1-IGF1R interaction. Adnexal involvement can predict AMis with higher invasive potential whereas APOE and CD163 serve as prognostic biomarkers for iAM. Altogether, our results provide implications for the early detection and treatment of AM.

Boron Cluster Renders Organic Radicals Water-Stable for Photothermal Anti-Infections.

Water-stable organic radicals are promising photothermal conversion candidates for photothermal therapy (PTT). However, organic radicals are usually unstable in biological environments, which greatly hinders their wide application. Here, we have developed a chaotropic effect-based and photoinduced water-stable supramolecular radical (MB12-2) for efficient antibacterial PTT. The supramolecular radical precursor MB12-1 was constructed by the chaotropic effect between closo-dodecaborate cluster (B12H122-) and N,N'-dimethylated dipyridinium thiazolo [5,4-d] thiazole (MPT2+). Subsequently, with triethanolamine (TEOA) serving as an electron donor, MB12-1 could transform to its radical form MB12-2 through photoinduced electron transfer (PET) under 435-nm laser irradiation. The N2 adsorption-desorption analysis confirmed that MB12-2 was tightly packed through the introduction of B12H122-, which effectively enhanced its stability via a spatial site-blocked effect. Moreover, the half-life of MB12-2 in water was calculated through ultraviolet-visible light (UV-vis) absorption spectra results for periods as long as 20 days. In addition, in the skin infection model, MB12-2, as a wound dressing, showed remarkable photothermal antibacterial activity (>97%) under 660-nm laser irradiation and promoted wound healing. This study presents a simple method for designing long-term water-stable supramolecular radicals, offering a novel avenue for noncontact treatments for bacterial infections.

Suppressed thermal transport in silicon nanoribbons by inhomogeneous strain.

Nanoscale structures can produce extreme strain that enables unprecedented material properties, such as tailored electronic bandgap1-5, elevated superconducting temperature6,7 and enhanced electrocatalytic activity8,9. While uniform strains are known to elicit limited effects on heat flow10-15, the impact of inhomogeneous strains has remained elusive owing to the coexistence of interfaces16-20 and defects21-23. Here we address this gap by introducing inhomogeneous strain through bending individual silicon nanoribbons on a custom-fabricated microdevice and measuring its effect on thermal transport while characterizing the strain-dependent vibrational spectra with sub-nanometre resolution. Our results show that a strain gradient of 0.112% per nanometre could lead to a drastic thermal conductivity reduction of 34 ± 5%, in clear contrast to the nearly constant values measured under uniform strains10,12,14,15. We further map the local lattice vibrational spectra using electron energy-loss spectroscopy, which reveals phonon peak shifts of several millielectron-volts along the strain gradient. This unique phonon spectra broadening effect intensifies phonon scattering and substantially impedes thermal transport, as evidenced by first-principles calculations. Our work uncovers a crucial piece of the long-standing puzzle of lattice dynamics under inhomogeneous strain, which is absent under uniform strain and eludes conventional understanding.

Osteomyelitis of the femur caused by Metamycoplasma orale in an immunocompromised patient using metagenomic next-generation sequencing: A case report.

Background: Metamycoplasma orale (M.orale), a symbiotic bacterium observed in the human oral cavity, is generally regarded as non-pathogenic to humans. Although infrequent, symptomatic infections caused by M.orale may occur in individuals with compromised humoral immunity. Accurate identification and early diagnosis of M.orale still present significant challenges due the limitations associated with conventional detection methods. Although metagenomic next-generation sequencing (mNGS) is currently widely utilized in clinical practices and exhibits a remarkable specificity and sensitivity for detecting various pathogens, its application in the diagnosis of M.orale-induced osteomyelitis remains largely unexplored. Case description: In this report, we present a case study of osteonecrosis caused by M.orale in a 20-year-old female patient with nephrotic syndrome and other comorbidities. She was administered long-term hormone therapy and immunosuppressants, leading to her admission to the hospital due to recurrent fever, hip abscess and left thigh pain. Imaging examination revealed bilateral mid-femoral lesions, with the extensive nature of the left femoral lesion suggesting a potential secondary infection. Although no pathogen was detected in pus culture, mNGS analysis identified M.orale in the sample. Following treatment with doxycycline and levofloxacin, the patient's symotoms improved and she was discharged with favorable outcomes. Conclusion: mNGS enables rapid identification of etiology in patients with osteomyelitis caused by the rare pathogen M.orale. This case accentuate the strength of mNGS for early detection and targeted clinical treatment of infectious diseases caused by uncommon pathogens.

Domino Michael/Oxa-Michael Reactions of the Unsymmetric Double Michael Acceptor for Access to Bicyclic Furo[2,3-b]pyrrole.

By creating an unsymmetric double Michael acceptor 1, we were able to synthesize the nonaromatic-fused bicyclic furo[2,3-b]pyrrole nucleus using a domino Michael/oxa-Michael reaction. Adopting benzoyl acetonitrile 2d (CN as the electron-withdrawing group) as a substrate, we discovered a (DHQ)2AQN-catalyzed method for high diastereo- and enantioselectivity of those products. The reaction path has been determined by isolating the reaction intermediates, and density functional theory calculations support these findings. Beyond providing a synthetic approach, this work illustrated the compounds' possible use in antitumor activity.