Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis.

The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15+ macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (TH2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.

Suppression of proteolipid protein rescues Pelizaeus-Merzbacher disease.

Mutations in PLP1, the gene that encodes proteolipid protein (PLP), result in failure of myelination and neurological dysfunction in the X-chromosome-linked leukodystrophy Pelizaeus-Merzbacher disease (PMD)1,2. Most PLP1 mutations, including point mutations and supernumerary copy variants, lead to severe and fatal disease. Patients who lack PLP1 expression, and Plp1-null mice, can display comparatively mild phenotypes, suggesting that PLP1 suppression might provide a general therapeutic strategy for PMD1,3-5. Here we show, using CRISPR-Cas9 to suppress Plp1 expression in the jimpy (Plp1jp) point-mutation mouse model of severe PMD, increased myelination and restored nerve conduction velocity, motor function and lifespan of the mice to wild-type levels. To evaluate the translational potential of this strategy, we identified antisense oligonucleotides that stably decrease the levels of Plp1 mRNA and PLP protein throughout the neuraxis in vivo. Administration of a single dose of Plp1-targeting antisense oligonucleotides in postnatal jimpy mice fully restored oligodendrocyte numbers, increased myelination, improved motor performance, normalized respiratory function and extended lifespan up to an eight-month end point. These results suggest that PLP1 suppression could be developed as a treatment for PMD in humans. More broadly, we demonstrate that oligonucleotide-based therapeutic agents can be delivered to oligodendrocytes in vivo to modulate neurological function and lifespan, establishing a new pharmaceutical modality for myelin disorders.

Does skin prick test response intensity predict symptom severity and efficacy of subcutaneous immunotherapy in allergic rhinitis?

OBJECTIVES: To investigate the effect of response intensity of allergen skin prick test (SPT) on symptom severity and long-term efficacy of dust mite subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR). METHODS: AR Patients diagnosed with dust mite allergy and completed 3 years of SCIT were collected and classified into three groups: grade 2 (SPT of + +), grade 3 (SPT of + + +) and grade 4 (SPT of + + + +). Comparisons between groups were performed to examine the associations of SPT categories and symptom severity and the long-term efficacy of SCIT in AR. RESULTS: 181 AR patients were included. There was no significant difference in the baseline TNSS, SMS, RQLQ and VAS, and particularly to symptom severity grading among three SPT grade groups (P > 0.05). The moderate-severe AR was more likely to be smoking and accompany with asthma and had higher prevalence of sensitization to cockroach, mixed grass and tree pollen than mild AR (P < 0.05). Prevalence of sensitization to cockroach, mixed grass, ragweed and animal dander was increased in AR patients with asthma and allergic conjunctivitis (P < 0.05). Furthermore, after 3 years of SCIT, no statistical differences in TNSS, SMS, RQLQ, VAS and long-term efficacy were observed among the three SPT grade groups (P > 0.05). Similarly, long-term outcomes of patients with different SPT grades did not differ among different clinical characteristics and different efficacy determination criteria (P > 0.05). CONCLUSIONS: The SPT response intensity cannot be used as an objective evaluation index for symptom severity and the long-term efficacy of SCIT in AR patients.

Identification of FtfL as a novel target of berberine in intestinal bacteria.

BACKGROUND: Berberine (BBR) is a commonly used anti-intestinal inflammation drug, and its anti-cancer activity has been found recently. BBR can intervene and control malignant colorectal cancer (CRC) through intestinal microbes, but the direct molecular target and related mechanism are unclear. This study aimed to identify the target of BBR and dissect related mechanisms against the occurrence and development of CRC from the perspective of intestinal microorganisms. RESULTS: Here, we found that BBR inhibits the growth of several CRC-driving bacteria, especially Peptostreptococcus anaerobius. By using a biotin-conjugated BBR derivative, we identified the protein FtfL (formate tetrahydrofolate ligase), a key enzyme in C1 metabolism, is the molecular target of BBR in P. anaerobius. BBR exhibits strong binding affinity and potent inhibition on FtfL. Based on this, we determined the crystal structure of PaFtfL (P. anaerobius FtfL)-BBR complex and found that BBR can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active center. In addition, the enzymatic activities of FtfL homologous proteins in human tumor cells can also be inhibited by BBR. CONCLUSIONS: In summary, our study has identified FtfL as a direct target of BBR and uncovered molecular mechanisms involved in the anti-CRC of BBR. BBR interferes with intestinal pathogenic bacteria by targeting FtfLs, suggesting a new means for controlling the occurrence and development of CRC.

Protein acetylation-mediated cross regulation of acetic acid and ethanol synthesis in the gas-fermenting Clostridium ljungdahlii.

The autotrophic acetogen Clostridium ljungdahlii has emerged as a major candidate in the biological conversion of one-carbon gases (CO2/CO) to bulk chemicals and fuels. Nevertheless, the regulatory pathways and downstream metabolic changes responsible for product formation and distribution in this bacterium remain minimally explored. Protein lysine acetylation (PLA), a prevalent posttranslational modification, controls numerous crucial cellular functions. Herein, we revealed a novel cross-regulatory mechanism that uses both the PLA system and transcription factors to regulate the carbon flow distribution for product formation in C. ljungdahlii. The dominant acetylation/deacetylation system (At2/Dat1) in C. ljungdahlii was found to regulate the ratio of two major products, acetic acid and ethanol. Subsequent genetic and biochemical analyses revealed that the activities of Pta and AdhE1, two crucial enzymes responsible for acetic acid and ethanol synthesis, respectively, were greatly affected by their levels of PLA. We found that the acetylation statuses of Pta and AdhE1 underwent significant dynamic changes during the fermentation process, leading to differential synthesis of acetic acid and ethanol. Furthermore, the crucial redox-sensing protein Rex was shown to be regulated by PLA, which subsequently altered its transcriptional regulation on genes responsible for acetic acid and ethanol formation and distribution. Based on our understanding of this cross-regulatory module, we optimized the ethanol synthetic pathway by modifying the acetylation status (deacetylation-mimicked mutations of crucial lysine residues) of the related key enzyme, achieving significantly increased titer and yield of ethanol, an important chemical and fuel, by C. ljungdahlii in gas fermentation.

RNA modifications in cancer.

Currently, more than 170 modifications have been identified on RNA. Among these RNA modifications, various methylations account for two-thirds of total cases and exist on almost all RNAs. Roles of RNA modifications in cancer are garnering increasing interest. The research on m6A RNA methylation in cancer is in full swing at present. However, there are still many other popular RNA modifications involved in the regulation of gene expression post-transcriptionally besides m6A RNA methylation. In this review, we focus on several important RNA modifications including m1A, m5C, m7G, 2'-O-Me, Ψ and A-to-I editing in cancer, which will provide a new perspective on tumourigenesis by peeking into the complex regulatory network of epigenetic RNA modifications, transcript processing, and protein translation.

Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): Study protocol for a randomized, blinded, crossover trial.

BACKGROUND: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown. OBJECTIVE: To evaluate and compare the efficacy and safety of half-dose quadruple therapy vs standard-dose dual therapy in the initial treatment of hypertensive patients with systolic/diastolic blood pressure 140-179/90-109 mm Hg. METHODS: A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mm Hg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to 2 crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. The patients will be followed up for 4 weeks to compare the antihypertensive effects and related adverse effects of the 2 antihypertensive combination treatments. CONCLUSIONS: We present the rationale for the design of the QUADUAL trial. The trial started in July 2022 and is expected to be completed by August 2023. The study aims to evaluate if an initial treatment regimen of quadruple combination of half-dose blood pressure medications will result in greater reduction in blood pressure and fewer side effects compared to standard dose dual therapy. REGISTRATION: www. CLINICALTRIALS: gov (NCT05377203).

Evaluation of Intralymphatic Immunotherapy in Allergic Rhinitis Patients: A Systematic Review and Meta-analysis.

Background: Intralymphatic immunotherapy (ILIT) is short-course administration of allergen-specific immunotherapy (AIT). This study is aimed at assessing the clinical efficacy and safety of ILIT in patients with allergic rhinitis (AR). Methods: MEDLINE, PUBMED, and Cochrane Library were used to conduct electronic searches for clinical trials comparing ILIT and placebo in patients with AR. The final search took place on August 24, 2022. Cochrane Handbook for Systematic Reviews of Interventions was used to assess the risk of bias in the included studies. The outcomes included combined symptom and medication scores (CSMS), visual analog scale (VAS), allergic rhinoconjunctivitis quality of life (RQLQ), Skin-prick test (SPT), and adverse events (AEs). Data were synthesized as mean difference (MD)/standard mean difference (SMD) or risk difference (RD) and 95% confidence interval (CI). Results: Thirteen studies (454 participants) were included in this study. The ILIT group had better clinical improvement on the CSMS (random effects model, SMD-0.85, 95% CI [-1.58, -0.11], P = 0.02) and RQLQ (fixed-effects model, MD-0.42, 95% CI [0.69, 0.15], P = 0.003) than the placebo group. The booster injection was beneficial for CSMS (P < 0.0001), and the 4-week injection interval was superior to the 2-week injection period for improving VAS (P < 0.0001). Local swelling or erythema was the main AE following injection (random effects model, RD 0.16, 95% CI [0.05, 0.27], P = 0.005). Discussion. For individuals with AR, ILIT is safe and effective. ILIT alleviates clinical symptoms and reduces pharmaceutical consumption without causing severe AEs. However, the validity of this study is compromised by the substantial heterogeneity and risk of bias in the included researches. RegistrationCRD42022355329.

Elevated body mass index increased the risk of recurrence in Chinese patients with chronic rhinosinusitis.

BACKGROUND: Elevated body mass index (BMI) has been associated with an increased prevalence of chronic rhinosinusitis (CRS). However, the impact of BMI on the risk of recurrence of CRS is unknown. This study aimed to investigate the association between BMI and the risk of CRS recurrence. MATERIAL AND METHODS: A retrospective cohort study was conducted and recruited 1057 CRS patients who underwent functional endoscopic sinus surgery (FESS). All subjects were classified into four groups: "underweight", "normal weight", "overweight", and "obese". Multivariate regression analysis was performed to examine the associations between BMI categories and other factors and the risk of CRS recurrence. RESULTS: The rate of recurrent CRS was significantly higher in the overweight group and obese group than in the normal weight group (P < 0.05). Unadjusted and adjusted logistic regression analyses demonstrated that overweight and obesity exhibited an increased risk of CRS recurrence as compared to patients with normal weight (P < 0.05). Furthermore, all patients were divided into primary CRS group and recurrent CRS group, and the BMI, duration of disease and rate of allergic rhinitis were vastly increased in the recurrent group than in the primary group (P < 0.05). Univariate and multivariate regression analysis showed that BMI and duration of disease were the dominant risk factors of CRS recurrence (P < 0.05). CONCLUSION: Overweight and obesity presented significant impacts on the CRS recurrence, and elevated BMI were associated with an increased risk of CRS recurrence independently from traditional risk factors. A longer duration of disease was correlated with a higher risk of CRS recurrence.

Diagnostic value of combined pelvic floor ultrasound parameters for pelvic floor dysfunction and risk factors.

OBJECTIVE: To investigate the diagnostic value of pelvic floor ultrasound parameters in combination for pelvic floor dysfunction (PFD), and to explore the risk factors. METHODS: Forty PFD patients treated from April2019to December 2020(case group) and another 40 healthy women (control group) were enrolled. Their clinical data were collected, and both groups received three-dimensional (3D) ultrasound of the pelvic floor. The diagnostic value of pelvic floor ultrasound parameters for PFD was assessed by receiver operating characteristic (ROC) curves. The risk factors of PFD were evaluated by multivariate logistic regression analysis. RESULTS: The area under the ROC curve (AUC), sensitivity, and specificity of the parameters in combination for predicting PFD were 0.851 [95% confidence interval (CI): 0.743-0.959], 0.901, and 0.812, respectively, indicating acceptable accuracy. Results of logistic regression analysis revealed that spontaneous delivery, lateral episiotomy/laceration, and large bladder neck rotation angle, posterior urethrovesical angle (PUA), bladder neck tilt angle, bladder neck distance (BND), levator hiatus area (LHA) (at anal contraction), R-LHA and V-LHA were risk factors for PFD (p < 0.05), while physical exercise was a protective factor (p < 0.05). ROC curve analysis revealed that the AUC, sensitivity, and specificity of the forest map model were 0.822 (95% CI: 0.759-0.885), 0.942, and 0.601, respectively, indicating acceptable accuracy of the model. Internal data validation of the model demonstrated consistence of the predicted occurrence of PFD with the actual one. CONCLUSIONS: Spontaneous delivery, lateral episiotomy/laceration, and large bladder neck rotation angle, PUA, bladder neck tilt angle, BND, LHA (at anal contraction), R-LHA and V-LHA were risk factors for PFD.

Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the ß-TrCP/c-Myc/SRSF1 positive feedback loop.

BACKGROUND: Circular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC). METHODS: The expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level of circPVT1 in NPC cells and tissue samples. The association of expression level of circPVT1 with clinical properties of NPC patients was evaluated. Then, the effects of circPVT1 expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction between circPVT1 and ß-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between ß-TrCP and c-Myc in NPC cells. RESULTS: We find that circPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed that circPVT1 promotes the invasion and metastasis of NPC cells. Mechanistically, circPVT1 inhibits proteasomal degradation of c-Myc by binding to ß-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc by circPVT1 alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis of circPVT1 through coupling transcription with splicing, which forms a positive feedback for circPVT1 production. CONCLUSIONS: Our results revealed the important role of circPVT1 in the progression of NPC through the ß-TrCP/c-Myc/SRSF1 positive feedback loop, and circPVT1 may serve as a prognostic biomarker or therapeutic target in patients with NPC.

Crossregulation of rapamycin and elaiophylin biosynthesis by RapH in Streptomyces rapamycinicus.

Rapamycin is an important macrocyclic antibiotic produced by Streptomyces rapamycinicus. In the rapamycin biosynthetic gene cluster (BGC), there are up to five regulatory genes, which have been shown to play important roles in the regulation of rapamycin biosynthesis. Here, we demonstrated that the rapamycin BGC-situated LAL family regulator RapH co-ordinately regulated the biosynthesis of both rapamycin and elaiophylin. We showed that rapH overexpression not only resulted in enhanced rapamycin production but also led to increased synthesis of another type I polyketide antibiotic, elaiophylin. Consistent with this, rapH deletion resulted in decreased production of both antibiotics. Through real-time RT-PCR combined with ß-glucuronidase reporter assays, four target genes controlled by RapH, including rapL (encoding a lysine cyclodeaminase)/rapH in the rapamycin BGC and ela3 (encoding a LuxR family regulator)/ela9 (encoding a hypothetical protein) in the elaiophylin BGC, were identified. A relatively conserved signature sequence recognized by RapH, which comprises two 4-nt inverted repeats separated by 8-nt, 5'-GTT/AC-N8-GTAC-3', was defined. Taken together, our findings demonstrated that RapH was involved in co-ordinated regulation of two disparate BGCs specifying two unrelated antibiotics, rapamycin and elaiophylin. These results further expand our knowledge of the regulation of antibiotic biosynthesis in S. rapamycinicus. KEY POINTS: • The cluster-situated regulator RapH controlled the synthesis of two antibiotics. • Four promoter regions recognized by RapH were identified. • A 16-nt signature DNA sequence essential for RapH regulation was defined.

Developing an endogenous quorum-sensing based CRISPRi circuit for autonomous and tunable dynamic regulation of multiple targets in Streptomyces.

Quorum-sensing (QS) mediated dynamic regulation has emerged as an effective strategy for optimizing product titers in microbes. However, these QS-based circuits are often created on heterologous systems and require careful tuning via a tedious testing/optimization process. This hampers their application in industrial microbes. Here, we design a novel QS circuit by directly integrating an endogenous QS system with CRISPRi (named EQCi) in the industrial rapamycin-producing strain Streptomyces rapamycinicus. EQCi combines the advantages of both the QS system and CRISPRi to enable tunable, autonomous, and dynamic regulation of multiple targets simultaneously. Using EQCi, we separately downregulate three key nodes in essential pathways to divert metabolic flux towards rapamycin biosynthesis and significantly increase its titers. Further application of EQCi to simultaneously regulate these three key nodes with fine-tuned repression strength boosts the rapamycin titer by ∼660%, achieving the highest reported titer (1836 ± 191 mg/l). Notably, compared to static engineering strategies, which result in growth arrest and suboptimal rapamycin titers, EQCi-based regulation substantially promotes rapamycin titers without affecting cell growth, indicating that it can achieve a trade-off between essential pathways and product synthesis. Collectively, this study provides a convenient and effective strategy for strain improvement and shows potential for application in other industrial microorganisms.

The Role of Noncoding RNA in Airway Allergic Diseases through Regulation of T Cell Subsets.

Allergic rhinitis and asthma are common airway allergic diseases, the incidence of which has increased annually in recent years. The human body is frequently exposed to allergens and environmental irritants that trigger immune and inflammatory responses, resulting in altered gene expression. Mounting evidence suggested that epigenetic alterations were strongly associated with the progression and severity of allergic diseases. Noncoding RNAs (ncRNAs) are a class of transcribed RNA molecules that cannot be translated into polypeptides and consist of three major categories, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). Previous studies showed that ncRNAs were involved in the physiopathological mechanisms of airway allergic diseases and contributed to their occurrence and development. This article reviews the current state of understanding of the role of noncoding RNAs in airway allergic diseases, highlights the limitations of recent studies, and outlines the prospects for further research to facilitate the clinical translation of noncoding RNAs as therapeutic targets and biomarkers.

Predictive Value of Nasal Nitric Oxide and Serum NOS2 Levels in the Efficacy of Subcutaneous Immunotherapy in Pediatric Patients with Allergic Rhinitis.

Background: Subcutaneous immunotherapy (SCIT) is an effective therapy for allergic rhinitis (AR), but some AR patients still do not benefit from it. Nasal nitric oxide (nNO) and inducible nitric oxide synthase (iNOS/NOS2) act important roles in AR. This study aims to explore the abilities of serum NOS2 and nNO in predicting the clinical efficacy of SCIT in AR patients. Methods: We recruited 40 healthy controls (HCs) and 120 AR patients in this study. Serum NOS2 and nNO levels were compared between the two groups. In the AR group, patients underwent and finished 1-year of SCIT, and divided into the effective and ineffective groups, and the relationships between serum NOS2 and nNO levels and efficacy of SCIT were evaluated. Results: The serum NOS2 and nNO levels were higher in AR patients than HCs. In the effective group, the serum NOS2 and nNO levels were increased than the ineffective group. ROC curves presented that a combination of serum NOS2 and nNO exhibited promising predictive ability in predicting the clinical efficacy of SCIT. Conclusions: Serum NOS2 and nNO levels were enhanced in AR patients and might affect the efficacy of SCIT. The combined use of serum NOS2 and nNO levels could be a reliable and useful method for predicting the clinical efficacy of SCIT.

Accuracy and stability evaluation of different blood sampling methods in blood gas analysis in emergency patients: A retrospective study.

BACKGROUND: To evaluate the accuracy and stability of arterial blood gas (ABG) results by comparison with venous measurements from routine blood tests, and to compare the accuracy and performance of two sampling syringes, pre-heparinized syringe (PHS) and disposable arterial blood syringe (DABS), in ABG analysis. METHODS: We retrospectively analyzed the practical use of PHS and DABS in collecting ABG samples, involving 500 and 400 patients, respectively. For each patient, in addition to the ABG sample, a venous blood sample was also collected using a venous blood collection tube (VBCT) and used for routine blood tests. Accordingly, patients were referred to as the PHS + VBCT group and DABS + VBCT group. The correlation between arterial and venous values of each blood parameter in each group was evaluated using the interclass correlation coefficient (ICC). Bland-Altman was performed to evaluate the agreement between arterial and venous values and compare the performance of PHS and DABS in ABG sample collection. RESULTS: In the PHS + VBCT group, arterial K+ , Na+ , hemoglobin (Hb), and hematocrit (HCT) were 0.32 mmol/L, 2.90 mmol/L, 2.21 g/L, and 1.27% significantly lower their corresponding venous values while arterial Cl- was 7.60 mmol/L significantly higher than venous Cl- . In the DABS + VBCT group, arterial K+ and Na+ were 0.20 mmol/L and 1.19 mmol/L significantly lower while Cl- and HCT in arterial blood were 5.34 mmol/L and 0.66% significantly higher than their corresponding venous values. In both groups, arterial K+ , Na+ , Hb, and HCT values were highly consistent with their corresponding venous values, with all ICCs greater than 0.70, especially Hb and HCT. Bland-Altman analysis demonstrated that arterial K+ and Na+ were more consistent with venous counterparts in the DABS + VBCT group, with a narrower 95% limits of agreement than the PHS + VBCT group (K+ , -0.7-0.3 mmol/L vs. -1.1 to 0.5 mmol/L; Na+ , -5.8 to 3.4 mmol/L vs. -8.2 to 2.4 mmol/L). CONCLUSION: Arterial blood gas analysis of K+ , Na+ , Hb, and HCT using PHS or DABS for blood sampling is accurate and stable, especially DABS, which can provide clinicians with fast and reliable blood gas results.

Hemangiopericytoma/solitary fibrous tumor of the cranial base: a case series and literature review.

BACKGROUND: Hemangiopericytomas (HPCs) are uncommon soft tissue tumors. HPCs that grow in the cranial base are rare. Therefore, skull-base surgeons tend to overlook this disease. This study aimed to increase the awareness of HPCs by summarizing case data from our institution and related publications. We also aimed to contribute to the number of reported cases for future systematic reviews of HPCs. METHODS: This study included all patients who underwent surgery for HPC/solitary fibrous tumor (SFT) between August 2015 and August 2019. All surgeries were performed at Xiangya Hospital Central South University. We analyzed clinical characteristics, surgical highlights, treatment modalities, and outcomes. RESULTS: We included six patients, aged 32-64 years. Lesions were located in the parapharyngeal space in three patients, pterygopalatine fossa in two, and saddle area in one. All patients underwent nasal endoscopic endonasal surgery. In five patients, tumors involved the internal carotid artery (ICA). The exposure and protection of the ICA during surgery are challenging but critical to complete tumor removal. The 3-year overall survival(OS) rate was 66.7%. CONCLUSIONS: HPC/SFTs are rare tumors of the cranial base that are prone to recurrence. Cranial base HPC/SFTs are often closely associated with the ICA. To our knowledge, this case series reports the largest number of cases of HPCs associated with the ICA. We believe that there is a strong relationship between patient prognosis and whether the tumor encircles the ICA and whether the tumor is completely resected. To confirm this suggestion, more cases are needed for further analysis.

A young patient with recurrent myocardial infarction within a half month. / åŠæœˆå† åå¤å¿ƒè‚Œæ¢—æ­»é’å¹´æ‚£è€ 1例.

In this study, we reported a young male patient with acute chest pain who was diagnosed as myocardial infarction. The regular medication was performed following coronary intervention. Under such condition, this patient had 3 times myocardial infarction within a half month. The laboratory results showed that there might be a state of hypercoagulability. Aspirin combined with clopidogrel and other treatment were administrated. Meanwhile, the examination demonstrated that there was aspirin-resistant in the patient. The antiplatelet drug and extended anticoagulation therapy were carried out. There was no further myocardial infarction, and no coronary arteries stenosis was found in the re-examination angiography. Aspirin resistance and hypercoagulability should be considered when patients occurred the repeated myocardial infarction after regular medication and coronary intervention. Replacement of the antiplatelet treatment or combination with anticoagulant therapy is necessary in similar patient to avoid the sever consequence.

InAs/InP quantum dash buried heterostructure mode-locked laser for high capacity fiber-wireless integrated 5G new radio fronthaul systems.

We have developed and experimentally demonstrated a highly coherent and low noise InP-based InAs quantum dash (QDash) buried heterostructure (BH) C-band passively mode-locked laser (MLL) with a pulse repetition rate of 25 GHz for fiber-wireless integrated fronthaul 5G new radio (NR) systems. The device features a broadband spectrum providing over 46 equally spaced highly coherent and low noise optical channels with an optical phase noise and integrated relative intensity noise (RIN) over a frequency range of 10 MHz to 20 GHz for each individual channel typically less than 466.5 kHz and -130 dB/Hz, respectively, and an average total output power of ∼50 mW per facet. Moreover, the device exhibits low RF phase noise with measured RF beat-note linewidth down to 3 kHz and estimated timing jitter between any two adjacent channels of 5.5 fs. By using this QDash BH MLL device, we have successfully demonstrated broadband optical heterodyne based radio-over-fiber (RoF) fronthaul wireless links at 5G NR in the underutilized spectrum of around 25 GHz with a total bit rate of 16-Gb/s. The device performance is experimentally evaluated in an end-to-end fiber-wireless system in real-time in terms of error vector magnitude (EVM) and bit error rate (BER) by generating, transmitting and detecting 4-Gbaud 16-QAM RF signals over 0.5-m to 2-m free-space indoor wireless channel through a total length of 25.22 km standard single mode fiber (SSMF) with EVM and BER under 8.4% and 2.9 × 10-5, respectively. The intrinsic characteristics of the device in conjunction with its system transmission performance indicate that QDash BH MLLs can be readily used in fiber-wireless integrated systems of 5G and beyond wireless communication networks.

Identification of the cognate response regulator of the orphan histidine kinase OhkA involved in both secondary metabolism and morphological differentiation in Streptomyces coelicolor.

In the model actinomycete strain, Streptomyces coelicolor, an orphan histidine kinase (HK) named OhkA (encoded by SCO1596), which belongs to bacterial two-component regulatory systems (TCSs), has been identified as being involved in the regulation of both antibiotic biosynthesis and morphological development. However, its cognate response regulator (RR) remains unknown due to its isolated genetic location on the genome, which impedes the elucidation of the mechanism underlying OhkA-mediated regulation. Here, we identified the orphan RR OrrA (encoded by SCO3008) as the cognate RR of OhkA according to mutant phenotypic changes, transcriptomics analysis, and bacterial two-hybrid experiment. Considering that the partner RR of the orphan HK is also orphan, a library of mutants with in-frame individual deletion of these functionally unknown orphan RR-encoding genes were generated. Through phenotypic analysis, it was found that the ∆orrA mutant exhibited similar phenotypic changes as that of the ∆ohkA mutant, showing increased production of actinorhodin (ACT) and undecylprodigiosin (RED), and pink colony surface. Further transcriptomics analysis showed these two mutants exhibited highly similar transcriptomics profiles. Finally, the direct interaction between OhkA and OrrA was revealed by bacterial two-hybrid system. The identification of the partner RR of OhkA lays a good foundation for an in-depth elucidation of the molecular mechanism underlying OhkA-mediated regulation of development and antibiotic biosynthesis in Streptomyces. KEY POINTS: • OrrA was identified as the partner RR of the orphan histidine kinase OhkA. • The ∆orrA and ∆ohkA mutants showed similar phenotype and transcriptomic profiling. • Specific interaction of OrrA and OhkA was revealed by bacterial two-hybrid system.