Integrated femtosecond pulse generator on thin-film lithium niobate.

Integrated femtosecond pulse and frequency comb sources are critical components for a wide range of applications, including optical atomic clocks1, microwave photonics2, spectroscopy3, optical wave synthesis4, frequency conversion5, communications6, lidar7, optical computing8 and astronomy9. The leading approaches for on-chip pulse generation rely on mode-locking inside microresonators with either third-order nonlinearity10 or with semiconductor gain11,12. These approaches, however, are limited in noise performance, wavelength and repetition rate tunability 10,13. Alternatively, subpicosecond pulses can be synthesized without mode-locking, by modulating a continuous-wave single-frequency laser using electro-optic modulators1,14-17. Here we demonstrate a chip-scale femtosecond pulse source implemented on an integrated lithium niobate photonic platform18, using cascaded low-loss electro-optic amplitude and phase modulators and chirped Bragg grating, forming a time-lens system19. The device is driven by a continuous-wave distributed feedback laser chip and controlled by a single continuous-wave microwave source without the need for any stabilization or locking. We measure femtosecond pulse trains (520-femtosecond duration) with a 30-gigahertz repetition rate, flat-top optical spectra with a 10-decibel optical bandwidth of 12.6 nanometres, individual comb-line powers above 0.1 milliwatts, and pulse energies of 0.54 picojoules. Our results represent a tunable, robust and low-cost integrated pulsed light source with continuous-wave-to-pulse conversion efficiencies an order of magnitude higher than those achieved with previous integrated sources. Our pulse generator may find applications in fields such as ultrafast optical measurement19,20 or networks of distributed quantum computers21,22.

On-chip electro-optic frequency shifters and beam splitters.

Efficient frequency shifting and beam splitting are important for a wide range of applications, including atomic physics1,2, microwave photonics3-6, optical communication7,8 and photonic quantum computing9-14. However, realizing gigahertz-scale frequency shifts with high efficiency, low loss and tunability-in particular using a miniature and scalable device-is challenging because it requires efficient and controllable nonlinear processes. Existing approaches based on acousto-optics6,15-17, all-optical wave mixing10,13,18-22 and electro-optics23-27 are either limited to low efficiencies or frequencies, or are bulky. Furthermore, most approaches are not bi-directional, which renders them unsuitable for frequency beam splitters. Here we demonstrate electro-optic frequency shifters that are controlled using only continuous and single-tone microwaves. This is accomplished by engineering the density of states of, and coupling between, optical modes in ultralow-loss waveguides and resonators in lithium niobate nanophotonics28. Our devices, consisting of two coupled ring-resonators, provide frequency shifts as high as 28 gigahertz with an on-chip conversion efficiency of approximately 90 per cent. Importantly, the devices can be reconfigured as tunable frequency-domain beam splitters. We also demonstrate a non-blocking and efficient swap of information between two frequency channels with one of the devices. Finally, we propose and demonstrate a scheme for cascaded frequency shifting that allows shifts of 119.2 gigahertz using a 29.8 gigahertz continuous and single-tone microwave signal. Our devices could become building blocks for future high-speed and large-scale classical information processors7,29 as well as emerging frequency-domain photonic quantum computers9,11,14.

CSF1R inhibition reprograms tumor-associated macrophages to potentiate anti-PD-1 therapy efficacy against colorectal cancer.

PD-1 blockade therapy has made great breakthroughs in treatment of multiple solid tumors. However, patients with microsatellite-stable (MSS) colorectal cancer (CRC) respond poorly to anti-PD-1 immunotherapy. Although CRC patients with microstatellite instability (MSI) or microsatellite instability-high (MSI-H) can benefit from PD-1 blockade therapy, there are still some problems such as tumor recurrence. Tumor-associated macrophages (TAMs), most abundant immune components in tumor microenvironment (TME), largely limit the therapeutic efficacy of anti-PD-1 against CRC. The CSF1/CSF1R pathway plays a key role in regulating macrophage polarization, and blocking CSF1R signaling transduction may be a potential strategy to effectively reprogram macrophages and remodel TME. Here, we found that increasing expression of CSF1R in macrophages predicted poor prognosis in CRC cohort. Furthermore, we discovered a novel potent CSF1R inhibitor, PXB17, which significantly reprogramed M2 macrophages to M1 phenotype. Mechanically, PXB17 significantly blocked activation of PI3K/AKT/mTORC1 signaling, resulting in inhibition of cholesterol biosynthesis. Results from 3D co-culture system suggested that PXB17-repolarized macrophages could induce infiltration of CD8+ T lymphocytes in tumors and improve the immunosuppressive microenvironment. In vivo, PXB17 significantly halted CRC growth, with a stronger effect than PLX3397. In particular, PXB17 potently enhanced therapeutic activity of PD-1 mAb in CT-26 (MSS) model and prevented tumor recurrence in MC-38 (MSI-H) model by promoting formation of long-term memory immunity. Our study opens a new avenue for CSF1R in tumor innate and adaptive anti-tumor immunomodulatory activity and suggests that PXB17 is a promising immunotherapy molecule for enhancing the efficacy of PD-1 mAb or reducing tumor recurrence of CRC.

Sub-Gluteus Maximus Fascial Plane and Perineural Hydrodissection as Novel Treatment for Posterior Femoral Cutaneous Nerve Entrapment.

ABSTRACT: Posterior femoral cutaneous nerve (PFCN) entrapment due to overuse is rarely reported in the literature, and treatment is limited. Conventional treatment includes focused rehabilitation exercises, computed tomography-guided or magnetic resonance (MR)-guided nerve blocks, MR-guided cryoablation, and surgical decompression, but data for treatment validation and efficacy are lacking. Sub-gluteus maximus fascial plane and perineural hydrodissection may offer an effective alternative treatment for PFCN entrapment, especially given reports of successful cases with similar procedural techniques in other anatomical locations and structures.

How to Avoid Misdiagnosing Spontaneous Cervical Spinal Epidural Hematoma as Ischemic Stroke: 3 Case Reports and Literature Review.

When spontaneous cervical spinal epidural hematoma (SCEH) presents with hemiparesis, it can be misdiagnosed with ischemic stroke (IS), and the treatment of IS such as thrombolysis may deteriorate the symptoms of patients with SCEH, leading to worse sequelae or even death. We reported 3 SCEH patients who were initially suspected as IS in our center between Jun 2020 and April 2022 and analyzed their clinical characteristics together with 48 patients reported in the literature from Jan 1995 to April 2022. Two of the 3 SCEH patients had neck symptoms, while none of them presented cranial nerve symptoms. Cranial computed tomography (CT) scans were negative; however, abnormal signals in the cervical spinal canal were observed during cranial computed tomography angiography (CTA) and subsequent cervical CT confirmed the diagnosis of SCEH. All of them avoid mistreatment with recombinant tissue plasminogen activator (rt-PA). Subsequently, we analyzed the clinical characteristics of a total of 51 patients. Thirteen of them developed symptoms during activity. Neck pain was an important sign of SCEH because 35 patients had neck pain or neck discomfort. Sensory impairment was reported in a small proportion of patients (11/51), which varied a lot in the patients. Some special manifestations highly suggested spinal cord lesions and provided evidence for the early differential diagnosis of SCEH and stroke, but the incidence of which was quite low: ipsilateral Horner syndrome in 2 patients, Brown-Séquard syndrome in 2 cases, and Lhermitte's sign in 1 case. Only a minority (8/51) of the patients were correctly diagnosed at the emergency unit using cervical CT. Six patients were correctly diagnosed when performing CTA. A large portion of the cases (21/51) were first misdiagnosed as IS, but no responsible lesions were found on cranial magnetic resonance imaging (MRI), and subsequent cervical MRI confirmed the diagnosis. Sixteen patients were diagnosed with SCEH after the deterioration of symptoms. A total of 13 patients received rt-PA, and 10 of them had symptoms aggravation after thrombolysis. For patients with acute onset of hemiparesis but without cranial nerve symptoms, especially those accompanied by clinical features such as neck pain, ipsilateral Horner syndrome, Brown-Séquard syndrome, and Lhermitte's sign, SCEH should be highly suspected rather than stroke. Careful differential diagnosis should be performed with a comprehensive medical history and thorough physical examination. Cervical CT scan is a reasonable choice for quick differential diagnosis prior to administering potentially harmful therapy, especially rt-PA.

The role of murine M1 macrophages from different sources in unilateral ureteral obstruction.

Introduction: The unilateral ureteral obstruction (UUO) model is the most extensively used model to investigate chronic renal fibrosis. Macrophages play a critical role in the UUO model. We aimed to analyze the phenotype of macrophages from different sources activated in vitro and explore the role of M1 macrophages from various sources in UUO. Material and methods: C57BL/6 mice were randomly allocated to five different groups (n = 5 per group): the sham-operated control group, PBS-treated (UUO + PBS) group, bone marrow-derived M1 macrophage-treated (UUO + BM1) group, peritoneal M1 macrophage-treated (UUO + PM1) group, and splenic M1 macrophage-treated (UUO + SPM1) group. After M1 macrophages were injected into the tail vein of UUO-treated mice, renal fibrosis indexes were determined using HE, Masson staining, and α-SMA. Results: Compared to those in the UUO + PBS group, the pathological changes were much more severe in the UUO + BM1, UUO + PM1, and UUO + SPM1 groups. Compared to that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1 group, the collagen area in the UUO + PM1 group was higher at post-UUO day 5 (p < 0.01). The expression of α-SMA in the UUO + PM1 group was higher than that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1group (p < 0.001). Conclusions: The M1 macrophages cultured in vitro were reinjected into mice and aggravated kidney injury and fibrosis. Compared with BM1 and SPM1, PM1 demonstrated a stronger effect on inducing renal injury and fibrosis.

Prevalence of preoperative deep vein thrombosis in long bone fractures of lower limbs: a systematic review and meta-analysis.

BACKGROUND: There is a paucity of data regarding the prevalence of preoperative deep vein thrombosis (DVT) in patients with long bone (including femur, tibia and fibula) fractures of the lower limbs. We performed a meta-analysis to address the issue. METHODS: Electronic databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, the VIP database, CNKI, and the Wanfang database, were systematic searched for original articles that reported the prevalence of preoperative DVT in long bone fractures of the lower limbs from January 2016 to September 2021. The prevalence of preoperative DVT was pooled using random-effects models, and subgroups were established according to study type, detection method, sample size and fracture site. RESULTS: Twenty-three articles reporting on 18,119 patients were eligible. The overall pooled preoperative DVT prevalence was 24.1% (95% CI 19.3-28.8%). In different subgroups, the preoperative DVT prevalences were 18.2-27.3%, 15.2-28.6%, 23.1-24.9%, 18.2-26.0% and 23.2-23.4% for different study designs, sample sizes, age groups, detection methods and fracture sites, respectively. CONCLUSIONS: Despite the heterogeneity among studies, this systematic review suggests that the prevalence of preoperative DVT, which may seriously affect the prognosis of patients, is high. Therefore, greater efforts should be devoted to the improvement of screening and prevention strategies for preoperative DVT in lower-extremity long bone fractures. LEVEL OF EVIDENCE: Level III. Trial Registration The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42022324706.

Long-read genome assembly and genetic architecture of fruit shape in the bottle gourd.

The bottle gourd (Lagenaria siceraria, Cucurbitaceae) is an important horticultural crop exhibiting tremendous diversity in fruit shape. The genetic architecture of fruit shape variation in this species remains unknown. We assembled a long-read-based, high-quality reference genome (ZAAS_Lsic_2.0) with a contig N50 value over 390-fold greater than the existing reference genomes. We then focused on dissection of fruit shape using a one-step geometric morphometrics-based functional mapping approach. We identified 11 quantitative trait loci (QTLs) responsible for fruit shape (fsQTLs), reconstructed their visible effects and revealed syntenic relationships of bottle gourd fsQTLs with 12 fsQTLs previously reported in cucumber, melon or watermelon. Homologs of several well-known and newly identified fruit shape genes, including SUN, OFP, AP2 and auxin transporters, were comapped with bottle gourd QTLs.

Pivotal role of obliquus capitis inferior in torticaput revealed by single-photon emission computed tomography.

Torticaput is the most common primary form of cervical dystonia (CD). Obliquus capitis inferior (OCI) plays a major role in ipsilateral rotation of the head. The present study aimed to use single-photon emission computed tomography (SPECT/CT) to determine the involvement of OCI in torticaput and in torticaput associated with no-no tremor. We retrospectively analyzed the SPECT/CT images of 60 patients with torticaput as the main abnormal posture and ranked the affected muscles. The affected muscles in patients with no-no tremor were also ranked. The correlation between the radioactivity of OCI and the thickness of OCI measured by ultrasonography was analyzed. The agreement between SPECT/CT and electromyography in detecting OCI was also analyzed. After sternocleidomastoid muscle (81.7%), OCI was the second most affected muscle (70.0%) in torticaput, followed by splenius capitis (63.3%). In 23 patients with no-no tremor, OCI (78.3%) and sternocleidomastoid muscle (78.3%) were the most frequently affected muscles, followed by splenius capitis (69.6%). Furthermore, bilateral muscle involvement was commonly seen in patients with no-no tremor, especially for OCI (12/23) and sternocleidomastoid muscle (11/23). A positive correlation was found between the radioactivity and thickness of OCI (r = 0.330, P < 0.001). The total agreement rate between SPECT/CT and electromyography in the diagnosis of OCI excitement was 94.0%, with kappa value = 0.866 (P < 0.001). OCI plays a critical role in torticaput and no-no tremor. SPECT/CT could be a practical tool to help clinicians detect abnormally excited OCI.

Subsartorius Fascial Plane Hydrodissection as Novel Treatment for Hunter's Canal Syndrome.

ABSTRACT: Saphenous entrapment neuropathy in the distal thigh most commonly occurs at Hunter's canal and is characterized by neurologic symptoms distal to the midthigh in the saphenous nerve distribution. Presented is a 23-year-old active duty female service member with left medial knee pain worse with knee flexion and extension. Evaluation raised suspicion for saphenous nerve entrapment at Hunter's canal, and ultrasound-guided subsartorius fascial plane hydrodissection was performed in addition to focused rehabilitation of the adductor and core musculature. No reports of this treatment have been published to date. This case introduces ultrasound-guided subsartorius fascial plane hydrodissection as novel treatment in Hunter's canal syndrome.

Infectious Dermatoses in Sport: A Review of Diagnosis, Management, and Return-to-Play Recommendations.

ABSTRACT: Infectious dermatoses represent a significant source of morbidity and missed athletic participation among athletes. Close quarters and skin trauma from contact sports can lead to outbreaks among teams and athletic staff. The National Collegiate Athletic Association and National Federation of State High School Associations have published guidance with recommended management and return-to-play criteria for common fungal, bacterial, viral, and parasitic rashes. In addition to rapidly diagnosing and treating infectious dermatoses, team physicians should counsel athletes and athletic staff on proper equipment care and personal hygiene to reduce infection transmission. Clinicians should always consult sport and athlete governing bodies for sport-specific recommendations.

Deep Gluteal Syndrome: A Pain in the Buttock.

ABSTRACT: While buttock pain is a common complaint in sports medicine, deep gluteal syndrome (DGS) is a rare entity. DGS has been proposed as a unifying term referring to symptoms attributed to the various pain generators located in this region. While not all-inclusive, the diagnosis of DGS allows for focus on pathology of regionally associated muscles, tendons, and nerves in the clinical evaluation and management of posterior hip and buttock complaints. An understanding of the anatomic structures and their kinematic and topographic relationships in the deep gluteal space is pivotal in making accurate diagnoses and providing effective treatment. Because presenting clinical features may be unrevealing while imaging studies and diagnostic procedures lack supportive evidence, precise physical examination is essential in obtaining accurate diagnoses. Management of DGS involves focused rehabilitation with consideration of still clinically unproven adjunctive therapies, image-guided injections, and surgical intervention in refractory cases.

Integrated microwave acousto-optic frequency shifter on thin-film lithium niobate.

Electrically driven acousto-optic devices that provide beam deflection and optical frequency shifting have broad applications from pulse synthesis to heterodyne detection. Commercially available acousto-optic modulators are based on bulk materials and consume Watts of radio frequency power. Here, we demonstrate an integrated 3-GHz acousto-optic frequency shifter on thin-film lithium niobate, featuring a carrier suppression over 30 dB. Further, we demonstrate a gigahertz-spaced optical frequency comb featuring more than 200 lines over a 0.6-THz optical bandwidth by recirculating the light in an active frequency shifting loop. Our integrated acousto-optic platform leads to the development of on-chip optical routing, isolation, and microwave signal processing.

Orphan genes are involved in drought adaptations and ecoclimatic-oriented selections in domesticated cowpea.

Orphan genes (OGs) are genes that are restricted to a single species or a particular taxonomic group. To date, little is known about the functions of OGs in domesticated crops. Here, we report our findings on the relationships between OGs and environmental adaptation in cowpea (Vigna unguiculata). We identified 578 expressed OGs, of which 73.2% were predicted to be non-coding. Transcriptomic analyses revealed a high rate of OGs that were drought inducible in roots when compared with conserved genes. Co-expression analysis further revealed the possible involvement of OGs in stress response pathways. Overexpression of UP12_8740, a drought-inducible OG, conferred enhanced tolerance to osmotic stresses and soil drought. By combining Capture-Seq and fluorescence-based Kompetitive allele-specific PCR (KASP), we efficiently genotyped single nucleotide polymorphisms (SNPs) on OGs across a 223 accession cowpea germplasm collection. Population genomic parameters, including polymorphism information content (PIC), expected heterozygosity (He), nucleotide diversity (π), and Tajima's D statistics, that were calculated based on these SNPs, showed distinct signatures between the grain- and vegetable-type subpopulations of cowpea. This study reinforces the idea that OGs are a valuable resource for identifying new genes related to species-specific environmental adaptations and fosters new insights that artificial selection on OGs might have contributed to balancing the adaptive and agronomic traits in domesticated crops in various ecoclimatic conditions.

Fine mapping Ruv2, a new rust resistance gene in cowpea (Vigna unguiculata), to a 193-kb region enriched with NBS-type genes.

KEY MESSAGE: A new rust resistance gene Ruv2 was fine-mapped in cowpea to a 193-kb region on chromosome 2, which harboured 23 predicted gene models enriched with NBS-type genes. ZN016 is a landrace vegetable cowpea highly resistant to rust. Two previous studies using mixed-spores inoculation suggested different modes of inheritance of rust resistance in ZN016. In this study, we initially developed a detached leaf assay with a purified single-rust isolate (Auv-LS). Using this approach, we assessed the inheritance of rust resistance in a recombinant inbred line (RIL) population and an F2 population, both derived from the cross of "ZN016" and the susceptible cultivar "Zhijiang282." A single dominant gene mode against Auv-LS was revealed in both populations. QTL mapping showed that this gene was coincident with the Ruv2 locus on LG7, one of the three resistance QTLs previously mapped based on mixed-spores inoculation data. Therefore, Ruv2 was considered as specifically against the rust isolate Auv-LS. Through an analysis of the RIL recombinants at Ruv2, we fine-mapped the gene to an ~ 0.45-cM interval between SNP markers 2_09656 and 2_00973, which corresponded to an ~ 193-kb region on chromosome 2 that harboured 23 predicted gene models enriched with NBS-type genes. Re-sequencing of the two parents revealed polymorphisms in four genes predictively to cause substantial protein structural changes, rendering them valuable candidate genes for future validation. Cross-species syntenic analysis indicated that Ruv2 may represent a novel rust resistance gene in food legumes. A cleaved amplified polymorphic sequences marker tightly linked to Ruv2 was developed to facilitate breeding. This work establishes a basis for map-based cloning of Ruv2 and breeding for rust resistance in cowpea and other legume crops.

Genomic regions, cellular components and gene regulatory basis underlying pod length variations in cowpea (V. unguiculata L. Walp).

Cowpea (V. unguiculata L. Walp) is a climate resilient legume crop important for food security. Cultivated cowpea (V. unguiculata L) generally comprises the bushy, short-podded grain cowpea dominant in Africa and the climbing, long-podded vegetable cowpea popular in Asia. How selection has contributed to the diversification of the two types of cowpea remains largely unknown. In the current study, a novel genotyping assay for over 50 000 SNPs was employed to delineate genomic regions governing pod length. Major, minor and epistatic QTLs were identified through QTL mapping. Seventy-two SNPs associated with pod length were detected by genome-wide association studies (GWAS). Population stratification analysis revealed subdivision among a cowpea germplasm collection consisting of 299 accessions, which is consistent with pod length groups. Genomic scan for selective signals suggested that domestication of vegetable cowpea was accompanied by selection of multiple traits including pod length, while the further improvement process was featured by selection of pod length primarily. Pod growth kinetics assay demonstrated that more durable cell proliferation rather than cell elongation or enlargement was the main reason for longer pods. Transcriptomic analysis suggested the involvement of sugar, gibberellin and nutritional signalling in regulation of pod length. This study establishes the basis for map-based cloning of pod length genes in cowpea and for marker-assisted selection of this trait in breeding programmes.